Composed of bone. Structure and chemical composition of bones

Each human bone is a complex organ: it occupies a certain position in the body, has its own shape and structure, and performs its own function. All types of tissues take part in bone formation, but bone tissue predominates.

General characteristics of human bones

Cartilage covers only the articular surfaces of the bone, the outside of the bone is covered with periosteum, and the bone marrow is located inside. Bone contains fatty tissue, blood and lymphatic vessels, and nerves.

Bone tissue has high mechanical qualities, its strength can be compared with the strength of metal. The chemical composition of human living bone contains: 50% water, 12.5% ​​organic protein substances (ossein), 21.8% inorganic substances (mainly calcium phosphate) and 15.7% fat.

Types of bones by shape divided into:

• Tubular (long - humeral, femoral, etc.; short - phalanges of the fingers);
• flat (frontal, parietal, scapula, etc.);
• spongy (ribs, vertebrae);
• mixed (sphenoid, zygomatic, lower jaw).

The structure of human bones

The basic structure of the unit of bone tissue is osteon, which is visible through a microscope at low magnification. Each osteon includes from 5 to 20 concentrically located bone plates. They resemble cylinders inserted into each other. Each plate consists of intercellular substance and cells (osteoblasts, osteocytes, osteoclasts). In the center of the osteon there is a canal - the osteon canal; vessels pass through it. Intercalated bone plates are located between adjacent osteons.

Bone tissue is formed by osteoblasts, secreting the intercellular substance and immuring itself in it, they turn into osteocytes - process-shaped cells, incapable of mitosis, with poorly defined organelles. Accordingly, the formed bone contains mainly osteocytes, and osteoblasts are found only in areas of growth and regeneration of bone tissue.

The largest number of osteoblasts is located in the periosteum - a thin but dense connective tissue plate containing many blood vessels, nerve and lymphatic endings. The periosteum ensures bone growth in thickness and nutrition of the bone.

Osteoclasts contain a large number of lysosomes and are capable of secreting enzymes, which can explain their dissolution of bone matter. These cells take part in the destruction of bone. In pathological conditions in bone tissue, their number increases sharply.

Osteoclasts are also important in the process of bone development: in the process of building the final shape of the bone, they destroy calcified cartilage and even newly formed bone, “correcting” its primary shape.

Bone structure: compact and spongy

On cuts and sections of bone, two of its structures are distinguished - compact substance(bone plates are located densely and orderly), located superficially, and spongy substance(bone elements are loosely located), lying inside the bone.

This bone structure fully complies with the basic principle of structural mechanics - to ensure maximum strength of the structure with the least amount of material and great lightness. This is also confirmed by the fact that the location of the tubular systems and the main bone beams corresponds to the direction of action of the compressive, tensile and torsional forces.

Bone structure is a dynamic reactive system that changes throughout a person's life. It is known that in people engaged in heavy physical labor, the compact layer of bone reaches a relatively large development. Depending on changes in the load on individual parts of the body, the location of the bone beams and the structure of the bone as a whole may change.

Connection of human bones

All bone connections can be divided into two groups:

• Continuous connections, earlier in development in phylogeny, immobile or sedentary in function;
• discontinuous connections, later in development and more mobile in function.

There is a transition between these forms - from continuous to discontinuous or vice versa - semi-joint.

The continuous connection of bones is carried out through connective tissue, cartilage and bone tissue (the bones of the skull itself). A discontinuous bone connection, or joint, is a younger formation of a bone connection. All joints have a general structural plan, including the articular cavity, articular capsule and articular surfaces.

Articular cavity stands out conditionally, since normally there is no void between the articular capsule and the articular ends of the bones, but there is liquid.

Bursa covers the articular surfaces of the bones, forming a hermetic capsule. The joint capsule consists of two layers, the outer layer of which passes into the periosteum. The inner layer releases fluid into the joint cavity, which acts as a lubricant, ensuring free sliding of the articular surfaces.

Types of joints

The articular surfaces of articulating bones are covered with articular cartilage. The smooth surface of articular cartilage promotes movement in the joints. Articular surfaces are very diverse in shape and size; they are usually compared to geometric figures. Hence name of joints based on shape: spherical (humeral), ellipsoidal (radio-carpal), cylindrical (radio-ulnar), etc.

Since the movements of the articulated links occur around one, two or many axes, joints are also usually divided according to the number of axes of rotation into multiaxial (spherical), biaxial (ellipsoidal, saddle-shaped) and uniaxial (cylindrical, block-shaped).

Depending on number of articulating bones joints are divided into simple, in which two bones are connected, and complex, in which more than two bones are articulated.

The teeth are located in bone sockets - separate cells of the alveolar processes of the upper and lower jaws. Bone tissue is a type of connective tissue that develops from the mesoderm and consists of cells, an intercellular non-mineralized organic matrix (osteoid) and the main mineralized intercellular substance.

5.1. ORGANIZATION AND STRUCTURE OF BONE TISSUE OF THE ALVEOLAR PROCESSES

The surface of the alveolar bone is covered periosteum(periosteum), formed predominantly by dense fibrous connective tissue, in which 2 layers are distinguished: the outer - fibrous and the inner - osteogenic, containing osteoblasts. Vessels and nerves pass from the osteogenic layer of the periosteum into the bone. Thick bundles of perforating collagen fibers connect the bone to the periosteum. The periosteum not only carries out a trophic function, but also participates in bone growth and regeneration. As a result, the bone tissue of the alveolar processes has a high regenerative ability not only under physiological conditions, under orthodontic influences, but also after damage (fractures).

The mineralized matrix is ​​organized into trabeculae - the structural and functional units of spongy bone tissue. Bone tissue cells - osteocytes, osteoblasts, osteoclasts - are located in the lacunae of the mineralized matrix and on the surface of the trabeculae.

The body constantly undergoes processes of bone tissue renewal through time-coupled bone formation and resorption (resorption) of bone. Various bone tissue cells actively participate in these processes.

Cellular composition of bone tissue

Cells occupy only 1-5% of the total volume of bone tissue of the adult skeleton. There are 4 types of bone tissue cells.

Mesenchymal undifferentiated bone cells are located mainly in the inner layer of the periosteum, covering the surface of the bone from the outside - the periosteum, as well as in the composition of the endosteum, lining the contours of all the internal cavities of the bone, the internal surfaces of the bone. They are called lining, or contour, cells. These cells can form new bone cells - osteoblasts and osteoclasts. In accordance with this function, they are also called osteogenic cells.

Osteoblasts- cells located in the zones of bone formation on the external and internal surfaces of the bone. Osteoblasts contain fairly large amounts of glycogen and glucose. With age, this amount decreases by 2-3 times. ATP synthesis is 60% associated with glycolysis reactions. As osteoblasts age, glycolytic reactions are activated. Reactions of the citrate cycle occur in cells, and citrate synthase has the greatest activity. The synthesized citrate is subsequently used to bind Ca 2+, necessary for mineralization processes. Since the function of osteoblasts is to create the organic extracellular matrix of bone, these cells contain large amounts of RNA necessary for protein synthesis. Osteoblasts actively synthesize and release into the extracellular space a significant amount of glycerophospholipids, which are capable of binding Ca 2+ and participating in mineralization processes. Cells communicate with each other through desmosomes, which allow the passage of Ca 2+ and cAMP. Osteoblasts synthesize and release collagen fibrils, proteoglycans and glycosaminoglycans into the environment. They also ensure the continuous growth of hydroxyapatite crystals and act as intermediaries in the binding of mineral crystals to the protein matrix. As we age, osteoblasts transform into osteocytes.

Osteocytes- tree-like cells of bone tissue, included in the organic intercellular matrix, which contact each other through processes. Osteocytes also interact with other bone tissue cells: osteoclasts and osteoblasts, as well as with mesenchymal bone cells.

Osteoclasts- cells that perform the function of bone destruction; are formed from macrophages. They carry out a continuous, controlled process of reconstruction and renewal of bone tissue, ensuring the necessary growth and development of the skeleton, structure, strength and elasticity of bones.

Intercellular and ground substance of bone tissue

Intercellular substance represented by an organic intercellular matrix built from collagen fibers (90-95%) and basic mineralized substance (5-10%). Collagen fibers are mainly located parallel to the direction of the level of the most likely mechanical loads on the bone and provide elasticity and elasticity to the bone.

Main substance The intercellular matrix consists mainly of extracellular fluid, glycoproteins and proteoglycans involved in the movement and distribution of inorganic ions. Mineral substances located as part of the main substance in the organic matrix of bone are represented by crystals, mainly hydroxyapatite Ca 10 (PO 4) 6 (OH) 2. The normal calcium/phosphorus ratio is 1.3-2.0. In addition, Mg 2+, Na +, K +, SO 4 2-, HCO 3-, hydroxyl and other ions were found in the bone, which can take part in the formation of crystals. Bone mineralization is associated with the characteristics of bone tissue glycoproteins and the activity of osteoblasts.

The main proteins of the extracellular matrix of bone tissue are type I collagen proteins, which make up about 90% of the organic matrix of bone. Along with collagen type I, there are traces of other types of collagen, such as V, XI, XII. It is possible that these types of collagen belong to other tissues, which are located in bone tissue, but are not part of the bone matrix. For example, type V collagen is typically found in the vessels that line bone. Type XI collagen is found in cartilage tissue and may correspond to remnants of calcified cartilage. The source of collagen type XII can be “blanks” of collagen fibrils. In bone tissue, type I collagen contains monosaccharide derivatives, has fewer cross-links than other types of connective tissue, and these bonds are formed through allysin. Another possible difference is that the N-terminal propeptide of type I collagen is phosphorylated and this peptide is partially retained in the mineralized matrix.

Bone tissue contains about 10% non-collagen proteins. They are represented by glycoproteins and proteoglycans (Fig. 5.1).

Of the total amount of non-collagen proteins, 10% are proteoglycans. First, large chondroitin is synthesized

Rice. 5.1.The content of non-collagen proteins in the intercellular matrix of bone tissue [according to Gehron R. P., 1992].

containing a proteoglycan, which, as bone tissue forms, is destroyed and replaced by two small proteoglycans: decorin and biglycan. Small proteoglycans are embedded in the mineralized matrix. Decorin and biglycan activate the processes of cell differentiation and proliferation, and are also involved in the regulation of mineral deposition, crystal morphology and the integration of organic matrix elements. Biglycan containing dermatan sulfate is synthesized first; it affects the processes of cell proliferation. During the mineralization phase, biglycan appears, bound to chondroitin sulfate. Decorin is synthesized later than biglycan, during the stage of protein deposition to form the intercellular matrix; it remains in the mineralization phase. It is believed that decorin “polishes” collagen molecules and regulates the diameter of fibrils. During bone formation, both proteins are produced by osteoblasts, but when these cells become osteocytes, they synthesize only biglycan.

Other types of small proteoglycans have been isolated from the bone matrix in small quantities, which act as

receptors and facilitate the binding of growth factors to the cell. These types of molecules are found in the membrane or attached to the cell membrane through phosphoinositol bonds.

Hyaluronic acid is also present in bone tissue. It probably plays an important role in the morphogenesis of this tissue.

In addition to proteoglycans, a large number of different proteins related to glycoproteins are detected in bone (Table 5.1).

Typically, these proteins are synthesized by osteoblasts and are capable of binding phosphate or calcium; thus they take part in the formation of the mineralized matrix. By binding to cells, collagens and proteoglycans, they ensure the formation of supramolecular complexes of the bone tissue matrix (Fig. 5.2).

The osteoid contains proteoglycans: fibromodulin, biglycan, decorin, collagen proteins and bone morphogenetic protein. Osteocytes, which are associated with collagens, are embedded in the mineralized matrix. Hydroxyapatites, osteocalcin, and osteoaderin are fixed on collagens. In the mineralized intercellular

Rice. 5.2.Participation of various proteins in the formation of the bone tissue matrix.

Table 5.1

Non-collagenous bone proteins

In the matrix, osteoaderin binds to osteonectin, and osteocalcin binds to collagen. Bone morphogenetic protein is located in the border zone between the mineralized and non-mineralized matrix. Osteopontin regulates the activity of osteoclasts.

The properties and functions of bone tissue proteins are presented in table. 5.1.

5.2. PHYSIOLOGICAL REGENERATION OF BONE TISSUE

In the process of life, the bone is constantly renewed, that is, destroyed and restored. At the same time, two oppositely directed processes occur in it - resorption and restoration. The relationship between these processes is called bone remodeling.

It is known that every 30 years bone tissue changes almost completely. Normally, bone “grows” until the age of 20, reaching peak bone mass. During this period, bone mass increases up to 8% per year. Then, until the age of 30-35, there is a period of more or less stable state. Then a natural gradual decrease in bone mass begins, usually amounting to no more than 0.3-0.5% per year. After menopause, women experience a maximum rate of bone loss, which reaches 2-5% per year and continues at this rate until 60-70 years. As a result, women lose 30 to 50% of their bone tissue. In men, these losses are usually 15-30%.

The process of bone tissue remodeling occurs in several stages (Fig. 5.3). At the first stage, the area of ​​bone tissue to be

Rice. 5.3.Stages of bone tissue remodeling [according to Martin R.B., 2000, as modified].

Resorption pressure is triggered by osteocytes. To activate the process, the participation of parathyroid hormone, insulin-like growth factor, interleukins-1 and -6, prostaglandins, calcitriol, and tumor necrosis factor is necessary. This stage of remodeling is inhibited by estrogen. At this stage, the superficial contour cells change their shape, turning from flat round cells to cubic ones.

Osteoblasts and T lymphocytes secrete receptor activator of nucleation factor kappa B (RANKL) ligands, and up to a certain point, RANKL molecules may remain associated with the surface of osteoblasts or stromal cells.

Osteoclast precursors are formed from bone marrow stem cells. They have membrane receptors called nucleation factor kappa B (RANK) receptors. At the next stage, RANK ligands (RANKL) bind to RANK receptors, which is accompanied by the fusion of several osteoclast precursors into one large structure and mature multinucleated osteoclasts are formed.

The resulting active osteoclast creates a corrugated edge on its surface and mature osteoclasts begin to resorb

bone tissue (Fig. 5.4). On the side where the osteoclast adheres to the destroyed surface, two zones are distinguished. The first zone is the most extensive, called the brush border, or corrugated edge. The corrugated edge is a spirally twisted membrane with multiple cytoplasmic folds that face the direction of resorption on the bone surface. Lysosomes containing a large number of hydrolytic enzymes (cathepsins K, D, B, acid phosphatase, esterase, glycosidases, etc.) are released through the osteoclast membrane. In turn, cathepsin K activates matrix metalloproteinase-9, which is involved in the degradation of collagen and proteoglycans of the intercellular matrix. During this period, carbonic anhydrase activity increases in osteoclasts. HCO 3 - ions are exchanged for Cl -, which accumulate in the corrugated edge; H + ions are also transferred there. Secretion of H + is carried out due to the very active H + /K + -ATPase in osteoclasts. Developing acidosis promotes the activation of lysosomal enzymes and contributes to the destruction of the mineral component.

The second zone surrounds the first and, as it were, seals the area of ​​action of hydrolytic enzymes. It is free from organelles and called

Rice. 5.4.Activation of the preosteoclast RANKL and the formation of a corrugated border by active osteoblasts, leading to bone resorption [according to Edwards P. A., 2005, as amended].

is a clear zone, so bone resorption occurs only under the corrugated edge in confined space.

At the stage of formation of osteoclasts from precursors, the process can be blocked by the protein osteoprotegerin, which, freely moving, is able to bind RANKL and thus prevent the interaction of RANKL with RANK receptors (see Fig. 5.4). Osteoprotegerin - glycoprotein with mol. weighing 60-120 kDa, belonging to the TNF receptor family. By inhibiting the binding of RANK to the RANK ligand, osteoprotegerin thereby inhibits the mobilization, proliferation and activation of osteoclasts, so an increase in RANKL synthesis leads to bone resorption and, consequently, bone loss.

The nature of bone tissue remodeling is largely determined by the balance between the production of RANKL and osteoprotegerin. Undifferentiated bone marrow stromal cells synthesize RANKL to a greater extent and osteoprotegerin to a lesser extent. The resulting imbalance of the RANKL/osteoprotegerin system with an increase in RANKL leads to bone resorption. This phenomenon is observed in postmenopausal osteoporosis, Paget's disease, bone loss due to cancer metastases and rheumatoid arthritis.

Mature osteoclasts begin to actively absorb bone, and macrophages complete the destruction of the organic matrix of the intercellular substance of the bone. Resorption lasts about two weeks. Then the osteoclasts die in accordance with the genetic program. Osteoclast apoptosis may be delayed by estrogen deficiency. At the last stage, pluripotent stem cells arrive in the destruction zone and differentiate into osteoblasts. Subsequently, osteoblasts synthesize and mineralize the matrix in accordance with new conditions of static and dynamic load on the bone.

There are a large number of factors that stimulate the development and function of osteoblasts (Fig. 5.5). The involvement of osteoblasts in the process of bone remodeling is stimulated by various growth factors - TGF-3, bone morphogenetic protein, insulin-like growth factor, fibroblast growth factor, platelets, colony-stimulating hormones - parathyrin, calcitriol, as well as nuclear binding factor α-1 and is inhibited by the protein leptin Leptin is a protein with a molecular weight of 16 kDa and is produced primarily in adipocytes; it acts through increased synthesis of cytokines, epithelial and keratinocyte growth factors.

Rice. 5.5.Bone tissue remodeling.

Active secreting osteoblasts create layers of osteoid, the non-mineralized bone matrix, and slowly replenish the resorption cavity. At the same time, they secrete not only various growth factors, but also proteins of the intercellular matrix - osteopontin, osteocalcin and others. When the resulting osteoid reaches a diameter of 6×10 -6 m, it begins to mineralize. The speed of the mineralization process depends on the content of calcium, phosphorus and a number of trace elements. The mineralization process is controlled by osteoblasts and inhibited by pyrophosphate.

The formation of bone mineral crystals is induced by collagen. The formation of the mineral crystal lattice begins in the zone located between the collagen fibrils. These in turn then become centers for deposition in the spaces between the collagen fibers (Fig. 5.6).

Bone formation occurs only in the immediate vicinity of osteoblasts, with mineralization beginning in cartilage,

Rice. 5.6.Deposition of hydroxyapatite crystals on collagen fibers.

which consists of collagen located in a proteoglycan matrix. Proteoglycans increase the extensibility of the collagen network. In the calcification zone, destruction of protein-polysaccharide complexes occurs as a result of hydrolysis of the protein matrix by lysosomal enzymes of bone cells. As the crystals grow, they displace not only proteoglycans, but also water. Dense, fully mineralized bone, practically dehydrated; collagen makes up 20% of the mass and 40% of the volume of such tissue; the rest is the share of the mineral part.

The onset of mineralization is characterized by increased absorption of O 2 molecules by osteoblasts, activation of redox processes and oxidative phosphorylation. Ca 2+ and PO 4 3- ions accumulate in mitochondria. The synthesis of collagen and non-collagen proteins begins, which are then secreted from the cell after post-translational modification. Various vesicles are formed, which contain collagen, proteoglycans and glycoproteins. Special formations called matrix vesicles or membrane vesicles bud from osteoblasts. They contain a high concentration of Ca 2+ ions, which is 25-50 times higher than their content in osteoblasts, as well as glycerophospholipids and enzymes - alkaline phosphatase, pyrophosphatase,

adenosine triphosphatase and adenosine monophosphatase. Ca 2+ ions in membrane vesicles are associated predominantly with negatively charged phosphatidylserine. In the intercellular matrix, membrane vesicles are destroyed with the release of Ca 2+ ions, pyrophosphates, and organic compounds associated with phosphoric acid residues. Phosphohydrolases present in membrane vesicles, and primarily alkaline phosphatase, cleave phosphate from organic compounds, and pyrophosphate is hydrolyzed by pyrophosphatase; Ca 2+ ions combine with PO 4 3-, which leads to the appearance of amorphous calcium phosphate.

At the same time, partial destruction of proteoglycans associated with type I collagen occurs. The released proteoglycan fragments, negatively charged, begin to bind Ca 2+ ions. A certain number of Ca 2+ and PO 4 3 ions form pairs and triplets that bind to collagen and non-collagen proteins that form the matrix, which is accompanied by the formation of clusters, or nuclei. Of the bone tissue proteins, osteonectin and matrix Gla proteins most actively bind Ca 2+ and PO 4 3 ions. Bone tissue collagen binds PO 4 3 ions through the ε-amino group of lysine to form a phosphoamide bond.

Spiral-shaped structures appear on the formed nucleus, the growth of which proceeds according to the usual principle of adding new ions. The pitch of such a spiral is equal to the height of one structural unit of the crystal. The formation of one crystal leads to the appearance of other crystals; this process is called epitaxy, or epitaxial nucleation.

Crystal growth is highly sensitive to the presence of other ions and molecules that inhibit crystallization. The concentration of these molecules can be small, and they affect not only the rate, but the shape and direction of crystal growth. It is assumed that such compounds are adsorbed on the surface of the crystal and inhibit the adsorption of other ions. Such substances are, for example, sodium hexametaphosphate, which inhibits the precipitation of calcium carbonate. Pyrophosphates, polyphosphates and polyphosphonates also inhibit the growth of hydroxyapatite crystals.

After a few months, after the resorption cavity is filled with bone tissue, the density of the new bone increases. Osteoblasts begin to transform into contour cells that are involved in the continuous removal of calcium from the bone. Some

Osteoblasts transform into osteocytes. Osteocytes remain in the bone; they are connected to each other by long cellular processes and are able to perceive mechanical forces on the bone.

As cells differentiate and age, the nature and intensity of metabolic processes changes. With age, the amount of glycogen decreases by 2-3 times; The released glucose in young cells is 60% used in anaerobic glycolysis reactions, and in old cells it is 85%. Synthesized ATP molecules are necessary for the life support and mineralization of bone cells. Only traces of glycogen remain in osteocytes, and the main supplier of ATP molecules is only glycolysis, due to which the constancy of the organic and mineral composition in the already mineralized sections of bone tissue is maintained.

5.3. REGULATION OF METABOLISM IN BONE TISSUE

Bone tissue remodeling is regulated by systemic (hormones) and local factors that ensure the interaction between osteoblasts and osteoclasts (Table 5.2).

System factors

Bone formation depends to a certain extent on the number and activity of osteoblasts. The process of osteoblast formation is influenced by

Table 5.2

Factors regulating bone remodeling processes

somatotropin (growth hormone), estrogens, 24,25(OH) 2 D 3, which stimulate the division of osteoblasts and the transformation of preosteoblasts into osteoblasts. Glucocorticoids, on the contrary, suppress the division of osteoblasts.

Parathyrin (parathyroid hormone) synthesized in the parathyroid glands. The parathyrin molecule consists of one polypeptide chain containing 84 amino acid residues. The synthesis of parathyrin is stimulated by adrenaline, therefore, under conditions of acute and chronic stress, the amount of this hormone increases. Parathyrins activate the proliferation of osteoblast precursor cells, prolong their half-life and inhibit osteoblast apoptosis. In bone tissue, receptors for parathyrin are present in the membranes of osteoblasts and osteocytes. Osteoclasts lack receptors for this hormone. The hormone binds to osteoblast receptors and activates adenylate cyclase, which is accompanied by an increase in the amount of 3 " 5" cAMP. This increase in cAMP content promotes an intensive supply of Ca 2+ ions from the extracellular fluid. The incoming calcium forms a complex with calmodulin, and then calcium-dependent protein kinase is activated, followed by protein phosphorylation. By binding to osteoblasts, parathyrin causes the synthesis of osteoclast-activating factor - RANKL, which can bind to preosteoclasts.

The administration of large doses of parathyrin leads to the death of osteoblasts and osteocytes, which is accompanied by an increase in the resorption zone, an increase in the level of calcium and phosphate in the blood and urine, with a simultaneous increase in the excretion of hydroxyproline due to the destruction of collagen proteins.

Receptors for parathyrin are also located in the renal tubules. In the proximal renal tubules, the hormone inhibits the reabsorption of phosphate and stimulates the formation of 1,25(OH) 2 D 3. In the distal parts of the renal tubules, parathyrin enhances the reabsorption of Ca 2+. Thus, parathyrin ensures an increase in calcium levels and a decrease in phosphates in the blood plasma.

Parotin -a glycoprotein secreted by the parotid and submandibular salivary glands. Protein consists of α-, β -, and γ-subunits. The active principle of parotin is the γ-subunit, which affects mesenchymal tissues - cartilage, tubular bones, tooth dentin. Parotin enhances the proliferation of chondrogenic cells, stimulates the synthesis of nucleic acids and DNA in odontoblasts, pro-

mineralization processes of dentin and bones. These processes are accompanied by a decrease in calcium and glucose levels in the blood plasma.

Calcitonin- a polypeptide consisting of 32 amino acid residues. Secreted by parafollicular K cells of the thyroid gland or C cells of the parathyroid glands as a high molecular weight precursor protein. The secretion of calcitonin increases with increasing concentration of Ca 2+ ions and decreases with decreasing concentration of Ca 2+ ions in the blood. It also depends on estrogen levels. With a lack of estrogen, the secretion of calcitonin decreases. This causes increased calcium mobilization in bone tissue and contributes to the development of osteoporosis. Calcitonin binds to specific receptors on osteoclasts and renal tubular cells, which is accompanied by activation of adenylate cyclase and increased formation of cAMP. Calcitonin affects the transport of Ca 2+ ions across cell membranes. It stimulates the uptake of Ca 2+ ions by mitochondria and thereby delays the outflow of Ca 2+ ions from the cell. This depends on the amount of ATP and the ratio of Na + and K + ions in the cell. Calcitonin inhibits the breakdown of collagen, which is manifested by a decrease in urinary excretion of hydroxyproline. In renal tubular cells, calcitonin inhibits the hydroxylation of 25(OH)D 3 .

Thus, calcitonin suppresses the activity of osteoclasts and inhibits the release of Ca 2+ ions from bone tissue, and also reduces the reabsorption of Ca 2+ ions in the kidneys. As a result, bone tissue resorption is inhibited and mineralization processes are stimulated, which is manifested by a decrease in the level of calcium and phosphorus in the blood plasma.

Iodine-containing hormones thyroid gland - thyroxine (T4) and triiodothyronine (T3) ensure optimal bone growth. Thyroid hormones can stimulate the secretion of growth hormones. They increase both the synthesis of insulin-like growth factor 1 (IGF-1) mRNA and the production of IGF-1 itself in the liver. In hyperthyroidism, the differentiation of osteogenic cells and protein synthesis in these cells are suppressed, and the activity of alkaline phosphatase is reduced. Due to the increased secretion of osteocalcin, osteoclast chemotaxis is activated, which leads to bone resorption.

Sex steroids hormones are involved in the processes of bone tissue remodeling. The effect of estrogens on bone tissue is manifested in the activation of osteoblasts (direct and indirect effects), inhibition of osteoclasts. They also promote the absorption of Ca 2+ ions in the gastrointestinal tract and its deposition in bone tissue.

Female sex hormones stimulate the production of calcitonin by the thyroid gland and reduce the sensitivity of bone tissue to parathyrin. They also competitively displace corticosteroids from their receptors in bone tissue. Androgens, having an anabolic effect on bone tissue, stimulate protein biosynthesis in osteoblasts, and are also aromatized in adipose tissue into estrogens.

In conditions of deficiency of sex steroids, which occurs in menopause, the processes of bone resorption begin to prevail over the processes of bone tissue remodeling, which leads to the development of osteopenia and osteoporosis.

Glucocorticoids synthesized in the adrenal cortex. The main glucocorticoid in humans is cortisol. Glucocorticoids act in a coordinated manner on different tissues and different processes - both anabolic and catabolic. In bone tissue, cortisol inhibits the synthesis of type I collagen, some non-collagen proteins, proteoglycans and osteopontin. Glucocorticoids also reduce the number of mast cells, which are the site of hyaluronic acid production. Under the influence of glucocorticoids, protein breakdown accelerates. Glucocorticoids suppress the absorption of Ca 2+ ions in the intestine, which is accompanied by a decrease in it in the blood serum. This decrease results in the release of parathyrin, which stimulates osteoclast formation and bone resorption (Fig. 5.7). In addition, cortisol in muscles and bones stimulates the breakdown of proteins, which also impairs bone formation. Ultimately, the actions of glucocorticoids lead to bone loss.

Vitamin D 3 (cholecalciferol) comes from food, and is also formed from the precursor 7-dehydrocholesterol under the influence of ultraviolet rays. In the liver, cholecalciferol is converted into 25(OH)D3, and in the kidneys further hydroxylation of 25(OH)D3 occurs and 2 hydroxylated metabolites are formed - 1,25(OH)2D3 and 24,25(OH)2D3. Metabolites of vitamin D 3 regulate chondrogenesis and osteogenesis already during embryonic development. In the absence of vitamin D 3, the mineralization of the organic matrix is ​​impossible, the vascular network is not formed, and the metaphyseal bone is not able to form properly. 1,25(OH) 2 D 3 binds to chondroblasts in an active state, and 24,25(OH) 2 D 3 binds to cells in a resting state. 1,25(OH) 2 D 3 regulates growth zones through the formation of a complex with the nuclear receptor for this vitamin. It has also been shown that 1,25(OH) 2 D 3 is capable of bonding

Rice. 5.7.Scheme of the influence of glucocorticoids on metabolic processes leading to bone loss

interact with the membrane-nuclear receptor, which leads to the activation of phospholipase C and the formation of inositol-3-phosphate. In addition, the resulting complex is activated by phospholipase A 2 . Prostaglandin E2 is synthesized from the released arachidonic acid, which also affects the response of chondroblasts when they bind to 1,25(OH)2D3. In contrast, after 24,25(OH)2D3 binds to its membrane-binding receptor, phospholipase C and then protein kinase C are activated.

In the cartilaginous growth zone of the epiphyses of bone tissue, 24,25(OH) 2 D 3 stimulates the differentiation and proliferation of prechondroblasts, which contain specific receptors for this metabolite. Metabolites of vitamin D 3 influence the formation and functional state of the temporomandibular joint.

Vitamin A. With a deficiency or excess intake of vitamin A into the body of children, bone growth is disrupted and their deformation occurs. These phenomena are probably due to the depolymerization and hydrolysis of chondroitin sulfate, which is part of the cartilage.

Vitamin C. With a lack of ascorbic acid in mesenchymal cells, hydroxylation of lysine and proline residues does not occur, which leads to disruption of the formation of mature collagen. The resulting immature collagen is not able to bind Ca 2+ ions and thus the mineralization processes are disrupted.

Vitamin E. With vitamin E deficiency, the liver does not produce 25(OH)D3, a precursor to active forms of vitamin D3. Vitamin E deficiency can also lead to low levels of magnesium in bone tissue.

Local factors

Prostaglandinsaccelerate the release of Ca 2+ ions from the bone. Exogenous prostaglandins increase the generation of osteoclasts, which destroy bone. They have a catabolic effect on protein metabolism in bone tissue and inhibit their synthesis.

Lactoferrin- iron-containing glycoprotein, in physiological concentrations stimulates the proliferation and differentiation of osteoblasts, and also inhibits osteoclastogenesis. The mitogenic effect of lactoferrin on osteoblast-like cells occurs through specific receptors. The resulting complex enters the cell through endocytosis, and lactoferrin phosphorylates mitogen-activating protein kinases. Thus, lactoferrin acts as a factor in bone growth and bone health. Can be used as an anabolic factor in osteoporosis.

Cytokines- low molecular weight polypeptides that determine the interaction of cells of the immune system. They provide a response to the introduction of foreign bodies, immune damage, as well as inflammation, repair and regeneration. They are represented by five large groups of proteins, one of which is interleukins.

Interleukins(IL) - proteins (from IL-1 to IL-18), synthesized mainly by T-cells of lymphocytes, as well as mononuclear phagocytes. The functions of IL are associated with the activity of other physiologically active peptides and hormones. At physiological concentrations, they inhibit cell growth, differentiation and lifespan. They reduce the production of collagenase, the adhesion of endothelial cells to neutrophils and eosinophils, the production of NO and, as a result, there is a decrease in the degradation of cartilage tissue and bone resorption.

The process of bone tissue resorption can be activated by acidosis and large amounts of integrins, IL and vitamin A, but is inhibited by estrogens, calcitonin, interferon and bone morphogenetic protein.

Bone turnover markers

Biochemical markers provide information about the pathogenesis of skeletal diseases and the phases of bone tissue remodeling. There are biochemical markers of bone formation and resorption that characterize the functions of osteoblasts and osteoclasts.

Prognostic significance of determining markers of bone tissue metabolism:

Screening using these markers allows us to identify patients at high risk of developing osteoporosis; high levels of bone resorption markers may be associated with

increased risk of fractures; an increase in the level of bone turnover markers in patients with osteoporosis by more than 3 times compared to normal values ​​suggests another bone pathology, including malignant; Resorption markers can be used as additional criteria when deciding whether to prescribe special therapy for the treatment of bone pathology. Bone resorption markers . During bone tissue renewal, type I collagen, which makes up more than 90% of the organic bone matrix and is synthesized directly in the bones, is degraded, and small peptide fragments enter the bloodstream or are excreted by the kidneys. Collagen degradation products can be determined both in urine and in blood serum. These markers can be used in therapy with drugs that reduce bone resorption in patients with diseases associated with disorders of bone metabolism. The criteria for bone tissue resorption are the degradation products of type I collagen: N- and C-telopeptides and tartrate-resistant acid phosphatase. In primary osteoporosis and Paget's disease, there is a clear increase in the C-terminal telopeptide of type I collagen and the amount of this marker in the blood serum increases by 2 times.

Collagen breakdown is the only source of free hydroxyproline in the body. The predominant part of hydroxyproline

is catabolized, and some is excreted in the urine, mainly in the composition of small peptides (di- and tripeptides). Therefore, the content of hydroxyproline in the blood and urine reflects the balance of the rate of collagen catabolism. In an adult, 15-50 mg of hydroxyproline is excreted per day, in a young age up to 200 mg, and in some diseases associated with collagen damage, for example: hyperparathyroidism, Paget's disease and hereditary hyperhydroxyprolinemia, which is caused by a defect in the enzyme hydroxyproline oxidase, the amount in the blood and hydroxyproline excreted in urine increases.

Osteoclasts secrete tartrate-resistant acid phosphatase. As osteoclast activity increases, the content of tartrate-resistant acid phosphatase increases and it enters the bloodstream in increased quantities. In the blood plasma, the activity of this enzyme increases in Paget's disease and cancer with metastases to the bone. Determination of the activity of this enzyme is especially useful in monitoring the treatment of osteoporosis and oncological diseases accompanied by damage to bone tissue.

Bone formation markers . Bone formation is assessed by the amount of osteocalcin, bone isoenzyme alkaline phosphatase and osteoprotegerin. Measuring the amount of serum osteocalcin allows us to determine the risk of developing osteoporosis in women, monitor bone metabolism during menopause and hormone replacement therapy. Rickets in young children is accompanied by a decrease in the content of osteocalcin in the blood, and the degree of decrease in its concentration depends on the severity of the rickets process. In patients with hypercortisolism and patients receiving prednisolone, the content of osteocalcin in the blood is significantly reduced, which reflects the suppression of bone formation processes.

The alkaline phosphatase isoenzyme is present on the cell surface of osteoblasts. With increased synthesis of the enzyme by bone tissue cells, its amount in the blood plasma increases, therefore, determining the activity of alkaline phosphatase, especially the bone isoenzyme, is an informative indicator of bone remodeling.

Osteoprotegerin acts as a TNF receptor. By binding to preosteoclasts, it inhibits the mobilization, proliferation and activation of osteoclasts.

5.4. REACTION OF BONE TISSUE TO DENTAL

IMPLANTS

For various forms of edentia, an alternative to removable prosthetics are intraosseous dental implants. The reaction of bone tissue to an implant can be considered a special case of reparative regeneration.

There are three types of connection between dental implants and bone tissue:

Direct engraftment - osseointegration;

Fibrous-osseous integration, when a layer of fibrous tissue about 100 microns thick is formed around the dental implant;

Periodontal junction (the rarest type), formed in the case of periodontal ligament-like fusion with peri-implantation collagen fibers or (in some cases) cementation of an intraosseous dental implant.

It is believed that during the process of osseointegration after the placement of dental implants, a thin zone of proteoglycans is formed, which is devoid of collagen. The bonding area of ​​the dental implant to the bone is provided by a double layer of proteoglycans, including decorin molecules.

With fibroosseous integration, numerous components of the extracellular matrix are also involved in the connection of the implant with the bone tissue. Type I and III collagens are responsible for the stability of the implant in its capsule, and fibronectin plays a major role in binding connective tissue elements to the implants.

However, after a certain period of time, under the influence of mechanical load, the activity of collagenase, cathepsin K and acid phosphatase increases. This leads to loss of bone tissue in the peri-implantation area and disintegration of the dental implant occurs. Early disintegration of intraosseous dental implants occurs against the background of a reduced amount of fibronectin, Gla protein, and tissue inhibitor of matrix metalloproteinases (TIMP-1) in the bone.

The average chemical composition of bone tissue includes 20-25% water, 75-80% dry matter, including 30% proteins and 45% inorganic compounds. However, tissue composition varies depending on the species and age of the animal, as well as the structure of the bone. The chemical composition of various types of cattle bones is presented in table. 5.5.

Table 55. Chemical composition of cattle bones

When bone tissue is treated with acids (hydrochloric, phosphoric, etc.), mineral substances dissolve and a soft organic part remains - ossein. The softening of bone due to the removal of minerals is called maceration. X

The structure of ossein consists mainly of protein substances - collagen (93%), ossemucoid, albumins, globulins, etc. The amino acid composition of bone is characterized by a low content of glutamic acid, lysine, and the absence of cystine and tryptophan; high content of glycine, proline, hydroxyproline, constituting up to 43% of the total amount of amino acids. Thus, bone proteins are not complete.

Of the organic compounds in bone tissue, there are lipids, in particular lecithin, citric acid salts, etc.

The most characteristic components of bone tissue are minerals, which make up half of the tissue mass. They are represented mainly by phosphorus-calcium salts, necessary for the life of the body, as well as microelements - Al, Mn, Cu, Pb, etc.

As the animal ages, along with a general increase in the content of minerals in the bone tissue, the content of carbonates increases and the amount of phosphates decreases. As a result of this change, the bones lose their elasticity and become fragile. Changes in bone properties may also be associated with a lack of certain salts in the diet, in particular with a lack of calcium during fattening. Electrical stunning of such cattle leads to fragmentation of the spine and pelvic bones.

The bone marrow that fills the bone marrow cavities contains mainly fats (up to 98% of the dry yellow marrow) and smaller amounts of choline phosphatides, cholesterol, proteins and minerals. The composition of fats is dominated by palmitic, oleic, and stearic acids.

In accordance with the characteristics of the chemical composition, bone is used for the production of semi-finished products, jellies, brawn, bone fat, gelatin, glue, and bone meal.

Cartilage tissue. Cartilage tissue performs supporting and mechanical functions. It consists of a dense ground substance in which round-shaped cells, collagen and elastin fibers are located (Fig. 5.14). Depending on the composition of the intercellular substance, hyaline, fibrous and elastic cartilages are distinguished. Hyaline cartilage covers the articular surfaces of bones, and the costal cartilages and trachea are built from it. Calcium salts are deposited in the intercellular substance of such cartilage with age. Hyaline cartilage is translucent and has a bluish tint.

Fibrous cartilage makes up the ligaments between the vertebrae, as well as the tendons and ligaments at their attachment to the bones. Fibrous cartilage contains many collagen fibers and a small amount of amorphous substance. It has the appearance of a translucent mass.

Elastic cartilage is cream-colored, the intercellular substance of which is dominated by elastin fibers. Lime is never deposited in elastic cartilage. It is part of the auricle and larynx.

The average chemical composition of cartilage tissue includes: 40-70% water,

19-20% proteins, 3.5% fats, 2-10% minerals, about 1% glycogen.

Cartilage tissue is characterized by a high content of mucoprotein - chondromucoid and mucopolysaccharide - chondroitinsulfuric acid in the main intercellular substance. An important property of this acid is its ability to form salt-like compounds with various proteins: collagen, albumin, etc. This apparently explains the “cementing” role of mucopolysaccharides in cartilage tissue.

Cartilage tissue is used for food purposes, and gelatin and glue are also produced from it. However, the quality of gelatin and glue is often not high enough, since mucopolysaccharides and glucoproteins pass into solution from the tissue along with gelatin, reducing the viscosity and strength of the jelly.

The intercellular organic matrix of compact bone makes up about 20%, inorganic substances - 70% and water - 10%. Organic components predominate in cancellous bone, accounting for more than 50%; inorganic compounds account for 33-40%. The amount of water is approximately the same as in a compact bone.

Organic bone tissue matrix. Approximately 95% of the organic matrix is ​​collagen type I. This type of collagen is also found in tendons and skin, but bone tissue collagen has some special features. It contains slightly more hydroxyproline, as well as free amino groups of lysine and oxylysine residues. This determines the presence of more cross-links in collagen fibers and their greater strength. Compared to collagen from other tissues, bone collagen is characterized by a higher content of phosphate, which is mainly associated with serine residues.

Proteins of non-collagenous nature are represented by glycoproteins, protein components of proteoglycans. They take part in the growth and development of bone, the process of mineralization, and water-salt metabolism. Albumins are involved in the transport of hormones and other substances from the blood.

The predominant protein of non-collagenous nature is osteocalcin. It is present only in bones and teeth. This is a small (49 amino acid residues) protein, also called bone glutamine protein or gla protein. Three residues are found in the osteocalcin molecule
γ-carboxyglutamic acid. Due to these residues, it is able to bind calcium. Vitamin K is required for the synthesis of osteocalcin (Fig. 34).

Rice. 34. Post-translational modification of osteocalcin

The organic matrix of bone tissue includes glycosaminoglycans, the main representative of which is chondroitin-4-sulfate. Chondroitin 6-sulfate, keratan sulfate and hyaluronic acid are contained in small quantities. Ossification is accompanied by a change in glycosaminoglycans: sulfated compounds give way to non-sulfated ones. Glycosaminoglycans are involved in the binding of collagen to calcium, regulation of water and salt metabolism.

Citrate is necessary for bone mineralization. It forms complex compounds with calcium and phosphorus salts, making it possible to increase their concentration in the tissue to a level at which crystallization and mineralization can begin. It will also take part in regulating calcium levels in the blood. In addition to citrate, succinate, fumarate, malate, lactate and other organic acids were found in bone tissue.

The bone matrix contains small amounts of lipids. Lipids play an essential role in the formation of crystallization nuclei during bone mineralization.

Osteoblasts are rich in RNA. The high RNA content in bone cells reflects their activity and constant biosynthetic function.

Inorganic composition of bone tissue.

At an early age, amorphous calcium phosphate Ca 3 (PO 4) 2 predominates in bone tissue. In mature bone, crystalline hydroxyapatite Ca 10 (PO 4) 6 (OH) 2 becomes predominant (Fig. 35). Its crystals are shaped like plates or rods. Typically, amorphous calcium phosphate is considered as a labile reserve of Ca 2+ and phosphate ions.

The composition of the mineral phase of bone includes ions of sodium, magnesium, potassium, chlorine, etc. In the crystal lattice of hydroxyapatite, Ca 2+ ions can be replaced by other divalent cations, while anions other than phosphate and hydroxyl are either adsorbed on the surface of the crystals or dissolved in hydration shell of the crystal lattice.

Rice. 35. Structure of hydroxyapatite crystal

Bone metabolism characterized by two opposing processes: the formation of new bone tissue by osteoblasts and the resorption (degradation) of old bone tissue by osteoclasts. Normally, the amount of newly formed tissue is equivalent to that destroyed. The bone tissue of the human skeleton is almost completely rebuilt within 10 years.

Bone formation

On Stage 1 osteoblasts first synthesize proteoglycans and glycosaminoglycans, which form the matrix, and then produce bone collagen fibrils, which are distributed in the matrix. Bone collagen is the matrix for the mineralization process. A necessary condition for the mineralization process is the supersaturation of the environment with calcium and phosphorus ions. The formation of bone mineral crystals is triggered by
Ca-binding proteins on the collagen matrix. Osteocalcin is tightly bound to hydroxyapatite and is involved in the regulation of crystal growth by binding Ca 2+ in bone. Electron microscopy studies have shown that the formation of a mineral crystal lattice begins in zones located in regular spaces between collagen fibrils. The resulting crystals in the collagen zone then in turn become mineralization nuclei, where hydroxyapatite is deposited in the space between the collagen fibers.

On Stage 2 in the mineralization zone, proteoglycans are degraded with the participation of lysosomal proteinases; Oxidative processes intensify, glycogen breaks down, and the required amount of ATP is synthesized. In addition, the amount of citrate necessary for the synthesis of amorphous calcium phosphate increases in osteoblasts.

As bone tissue mineralizes, hydroxyapatite crystals displace not only proteoglycans, but also water. Dense, fully mineralized bone is virtually dehydrated.

The enzyme alkaline phosphatase is involved in mineralization. One of the mechanisms of its action is a local increase in the concentration of phosphorus ions to the saturation point, followed by the processes of fixation of calcium-phosphorus salts on the organic matrix of the bone. When bone tissue is restored after fractures, the content of alkaline phosphatase in callus increases sharply. When bone formation is impaired, a decrease in the content and activity of alkaline phosphatase in bones, plasma and other tissues is observed.

The calcification inhibitor is inorganic pyrophosphate. A number of researchers believe that the process of collagen mineralization in the skin, tendons, and vascular walls is hampered by the constant presence of proteoglycans in these tissues.

The processes of modeling and remodeling ensure constant renewal of bones, as well as modification of their shape and structure. Modeling (new bone formation) occurs mainly in childhood. Remodeling is the dominant process in the adult skeleton; in this case, only a separate section of the old bone is replaced. Thus, under physiological and pathological conditions, not only formation, but also resorption of bone tissue occurs.

Bone catabolism

Almost simultaneously, “resorption” of both mineral and organic structures of bone tissue takes place. With osteolysis, the production of organic acids increases, which leads to a shift in pH to the acidic side. This helps dissolve mineral salts and remove them.

Resorption of the organic matrix occurs under the action of lysosomal acid hydrolases, the spectrum of which in bone tissue is quite wide. They participate in the intracellular digestion of fragments of resorbable structures.

In all skeletal diseases, disturbances in bone remodeling processes occur, which is accompanied by deviations in the level of biochemical markers.

There are common markers of new bone formation, such as bone-specific alkaline phosphatase, plasma osteocalcin, procollagen I, plasma peptides. To biochemical bone resorption markers include urinary calcium and hydroxyproline, urinary pyridinoline and deoxypyridinoline, which are derivatives of transverse collagen fibers specific to cartilage and bone.

Factors hormones, enzymes and vitamins that influence bone metabolism.

The mineral components of bone tissue are practically in a state of chemical equilibrium with calcium and phosphate ions in the blood serum. Parathyroid hormone and calcitonin play an important role in the regulation of the intake, deposition and release of calcium and phosphate.

The action of parathyroid hormone leads to an increase in the number of osteoclasts and their metabolic activity. Osteoclasts contribute to the accelerated dissolution of mineral compounds contained in bones. Thus, activation of cellular systems involved in bone resorption occurs.

Parathyroid hormone also increases the reabsorption of Ca 2+ ions in the renal tubules. The net effect is an increase in serum calcium levels.

The effect of calcitonin is to reduce the concentration of Ca 2+ ions due to its deposition in bone tissue. It activates the osteoblast enzyme system, increases bone mineralization and reduces the number of osteoclasts in the area of ​​action, i.e., inhibits the process of bone resorption. All this increases the rate of bone formation.

Vitamin D is involved in the biosynthesis of Ca 2+ -binding proteins, stimulates the absorption of potassium in the intestine, increases the reabsorption of calcium, phosphorus, sodium, citrate, and amino acids in the kidneys. With a lack of vitamin D, these processes are disrupted. Taking excessive amounts of vitamin D over a long period of time leads to demineralization of bones and an increase in calcium concentrations in the blood.

Corticosteroids increase the synthesis and secretion of parathyroid hormone and increase bone demineralization; sex hormones accelerate maturation and shorten the period of bone growth; thyroxine enhances tissue growth and differentiation.

The effect of vitamin C on bone tissue metabolism is primarily due to its influence on the process of collagen biosynthesis. Ascorbic acid is a cofactor for prolyl and lysyl hydroxylases and is necessary for the hydroxylation reaction of proline and lysine. A lack of vitamin C also leads to changes in the synthesis of glycosaminoglycans: the content of hyaluronic acid in bone tissue increases several times, while the biosynthesis of chondroitin sulfates slows down.

With a lack of vitamin A, changes in the shape of bones, impaired mineralization, and growth retardation occur. It is believed that this fact is due to a violation of the synthesis of chondroitin sulfate. High doses of vitamin A lead to excess bone resorption.

With a lack of B vitamins, bone growth slows down, which is associated with impaired protein and energy metabolism.

Features of dental tissue

The main part of the tooth is dentine. The part of the tooth that protrudes from the gums, the crown, is covered enamel, and the tooth root is covered dental cement. Cementum, dentin and enamel are built like bone tissue. The protein matrix of these tissues consists mainly of collagens and proteoglycans. The content of organic components in cement is about 13%, in dentin – 20%, in enamel – only 1-2%. The high content of mineral substances (enamel - 95%, dentin - 70%, cement - 50%) determines the high hardness of dental tissue. The most important mineral component is hydroxyapatite [Ca 3 PO 4) 2 ] 3 Ca(OH) 2 . Carbonate apatite, chlorapatite and strontium apatite are also contained.

The enamel covering the tooth is semi-permeable. It is involved in the exchange of ions and molecules with saliva. The permeability of enamel is influenced by the pH of saliva, as well as a number of chemical factors.

In an acidic environment, tooth tissue is attacked and loses its hardness. Such a common disease as caries, is caused by microorganisms living on the surface of teeth and releasing organic acids as a product of anaerobic glycolysis, which wash Ca 2+ ions from the enamel.

Security questions

1. Name the main organic components of bone tissue.

2. What inorganic compounds make up bone tissue?

3. What is the difference between the biochemical processes occurring in osteoclasts and osteoblasts?

4. Describe the process of bone formation.

5. What factors influence the formation of bone tissue and its metabolism?

6. What substances can be biochemical markers of processes occurring in bone tissue?

7. What are the features of the biochemical composition of dental tissue?

Literature

1. Berezov, T.T. Biological chemistry. / T.T. Berezov, B.F. Korovkin. - M.: OJSC “Publishing House “Medicine””, 2007. - 704 p.

2. Biochemistry. / Ed. E.S. Severina. - M.: GEOTAR-Media, 2014. -
768 pp.

3. Biological chemistry with exercises and problems. / Ed. E.S. Severina. - M.: GEOTAR-Media, 2013. - 624 p.

4. Zubairov, D.M. Guide to laboratory exercises in biological chemistry. / D.M. Zubairov, V.N. Timerbaev, V.S. Davydov. - M.: GEOTAR-Media, 2005. - 392 p.

5. Shvedova, V.N. Biochemistry. /V.N. Shvedova. – M.: Yurayt, 2014. – 640 p.

6. Nikolaev, A.Ya. Biological chemistry. / A.Ya. Nikolaev. - M.: Medical Information Agency, 2004. - 566 p.

7. Kushmanova, O.B. Guide to laboratory exercises in biological chemistry. / ABOUT. Kushmanova, G.I. Ivchenko. - M. - 1983.

8. Leninger, A. Fundamentals of biochemistry / A. Leninger. - M., “World”. - 1985.

9. Murray, R. Human biochemistry. / R. Murray, D. Grenner, P. Mayes, V. Rodwell. - T. 1. - M.: Mir, 1993. - 384 p.

10. Murray, R. Human biochemistry. / R. Murray, D. Grenner, P. Mayes, V. Rodwell. - T. 2. - M.: Mir, 1993. - 415 p.

The skeleton of any adult human includes 206 different bones, all of them different in structure and role. At first glance, they appear hard, inflexible and lifeless. But this is a mistaken impression; various metabolic processes, destruction and regeneration, continuously occur in them. They, together with muscles and ligaments, form a special system called “musculoskeletal tissue,” the main function of which is musculoskeletal. It is formed from several types of special cells that differ in structure, functional features and significance. Bone cells, their structure and functions will be discussed further.

The structure of bone tissue

This is a separate type of connective tissue; all bones in the human body are formed from it. It consists of special cells and intercellular substance. The latter includes an organic matrix consisting of collagen fibers (90-95% of the total mass) and mineral components, mainly calcium salts (5-10%). Thanks to this composition, human bone tissue has a harmonious combination of hardness and elasticity. There are three groups of cells: osteoclasts (left), osteoblasts (middle), osteocytes (right in the photo).

Let's look at them in more detail below. The collagen contained in the matrix differs from its counterparts found in other tissues, mainly due to the fact that it contains more specific polypeptides. The fibers are located, as a rule, parallel to the level of the most probable loads on the bone. It is thanks to it that elasticity and firmness are preserved.

If the bone is exposed to hydrochloric acid, the mineral substances will be dissolved, but the organic substances (ossein) will remain. They will retain their shape, but will become overly flexible and highly susceptible to deformation. This condition is typical for young children. They have a high ossein content, so their bones are more elastic than those of adults. And the opposite case occurs when organic substances are lost, but mineral substances remain. This happens if, for example, a bone is burned: it will retain its shape, but at the same time it will become very fragile and can collapse even from a slight touch. The composition of bone tissue undergoes such changes in old age. The share of mineral salts reaches 80% of the total mass. Therefore, older people are more susceptible to various types of fractures and injuries.

If you establish bone tissue density (volume), this will allow you to evaluate the strength of the skeleton and its individual parts. Such studies are carried out using computed tomography. Timely diagnosis allows you to start treatment or maintenance therapy on time.

Osteoblasts (active): structural features

Osteoblasts are bone tissue cells located in its upper layers, having a polygonal, cubic shape with various types of processes. The internal contents are not much different from others. A well-developed granular endoplasmic reticullum contains various elements, ribosomes, the Golgi apparatus, a round or oval-shaped nucleus rich in chromatin and containing a nucleolus. On the outside, these bone tissue cells are surrounded by the finest microfibrils.

The main function of osteoblasts is the synthesis of components of the intercellular substance. These are collagen (mainly the first type), matrix glycoproteins (osteocalcin, osteonectin, osteopontin, bone sialoprotein), proteoglycans (biglycan, hyaluronic acid, decorin), as well as various bone morphogenetic proteins, growth factors, enzymes, phosphoproteins. Impaired production of all these compounds by osteoblasts is observed in some diseases. For example, vitamin C deficiency (scurvy) in children is characterized by impaired bone development and growth due to a defect in the synthesis of collagen and glycosaminoglycans. For the same reason, the restoration of bone tissue and healing of fractures slows down. Since osteoblasts are actually responsible for growth, they are present exclusively in developing bone tissue.

Mechanism of mineralization of organic matrix by osteoblasts

There are two ways:

1. Deposition of hydroxylate crystals along collagen fibrils from supersaturated extracellular fluid. A special role is assigned to certain proteoglycans, which bind calcium and retain it in gap areas.
2. Secretion of special matrix vesicles. These are small membrane structures that are synthesized and secreted by osteoblasts. They contain high concentrations of calcium phosphate and alkaline phosphatase. The special microenvironment created inside the bubbles favors the formation of the first hydroxyapatite crystals.

The rate of mineralization of osteoid (bone tissue at the stage of formation) can vary significantly; normally it takes about 15 days. Disturbances can occur when the concentration of calcium or phosphate ions in the blood decreases. The result of this is softening and deformation of the bones - osteomalacia. Similar disorders are observed, for example, with rickets (vitamin D deficiency).

Inactive (resting) osteoblasts

They are formed from active osteoblasts; in non-growing bone they cover about 80-95% of its surface. They have a flattened shape with a fusiform nucleus. The remaining organelles are reduced. But receptors that respond to various hormones and growth factors are preserved. The connection between resting osteoblasts and osteocytes is maintained and thus a system is formed that regulates mineral metabolism. If any damage occurs (injuries, fractures), they are activated, and active collagen synthesis and the production of an organic matrix begin. In other words, due to them, bone tissue regeneration occurs. At the same time, they can be the cause of a malignant tumor - osteosarcoma.

Osteocytes: structure and functions

These cells form the basis of mature bone tissue. Their shape is spindle-shaped, with many branches. The organelles are significantly smaller compared to osteoblasts; there is a rounded nucleus (heteochromatin predominates in it) with a nucleolus. Osteocytes are located in lacunae, but do not directly contact the matrix, but are surrounded by a thin layer of bone fluid. It provides nutrition to the cells.

Their processes, which are quite long, up to 50 µm, and located in special tubules, are similarly separated. There are a lot of them, bone tissue is literally permeated with them, they form its drainage system, which contains tissue fluid. Through it, the exchange of substances between the intercellular substance and cells occurs. It is also worth noting that they do not divide, but are formed from osteoblasts and are the main components in the formed bone tissue.

The main function of osteocytes is to maintain the normal state of the bone matrix and the balance of calcium and phosphorus in the body. They are able to perceive mechanical stress and are sensitive to electrical potentials arising from the action of deforming forces. Reacting to them, they trigger a local process in which the connective bone tissue begins to rebuild.

Osteoclasts

This name was given to large cells containing from 5 to 100 nuclei, having a monocytic origin, destroying bones and cartilage or, in other words, causing their resorption. The cytoplasm of osteoclasts contains many mitochondria, elements of the ER (granular) and Golgi apparatus, ribosomes, as well as lysosomes of various functions. The nuclei contain a large amount of chromatin and have clearly visible nucleoli. There is also a sufficient number of cytoplasmic processes, most of them are located on the surface adjacent to the destroyed bone. They increase the area of ​​contact with it. Bone tissue begins to break down when the level of a special hormone (parathyroid) increases, which leads to the activation of osteoclasts. The mechanism of this process is associated with the release of carbon dioxide, which, under the influence of a special enzyme (carbonic anhydrase), is converted into an acid called carbonic acid, which dissolves calcium salts.

Mechanism of bone resorption

It is worth noting that the destruction process occurs cyclically, and periods of high activity of each cell are invariably followed by periods of rest. Resorption occurs in several stages:

1. Attachment of the osteoclast to the destructible surface of the bone, with a pronounced restructuring of its cytoskeleton observed.
2. Oxidation of the contents of lacunae. This occurs either by the release of vacuole contents, which have an acidic environment, or as a result of the action of proton pumps.
3. Destruction of the mineral component of the matrix.
4. Dissolution of organic compounds as a result of the action of enzymes secreted by osteoclasts into the lacuna and activated by an acidic environment.
5. Removal of bone tissue destruction products.

Regulation of osteoclast activity is determined by general and local factors. The first, for example, include parathyroid hormone and vitamin D, they stimulate activity. Calcitonin and estrogens are inhibitory. Local factors include such a factor as the creation of a local electric field under mechanical stress, to which these cells are very sensitive.

The structure of coarse-fiber bone tissue

Its second name is reticulofibrous. It is formed in the embryo as the future basis of bones. In an adult, its presence is minimal; it remains in the sutures of the skull after they heal and in areas where tendons are attached to bones, as well as in areas of osteogenesis, for example, during the healing of various types of fractures. The structure of the bone tissue of this species is specific. Collagen fibers are collected in dense bundles, which are arranged randomly and have “crossbars” between them. It has low mechanical strength, the content of osteocytes is significantly higher compared to the lamellar variety. In pathological conditions, this type of bone tissue growth occurs when a bone is fractured or in Paget's disease.

Features of lamellar bone tissue

It is formed by bone plates having a thickness of 4-15 microns. They, in turn, consist of three components: osteocytes, ground substance and collagen thin fibers. All bones of an adult are formed from this tissue. The collagen fibers of the first type lie parallel to each other and are oriented in a certain direction, while in neighboring bone plates they are directed in the opposite direction and intersect almost at a right angle. Between them are the bodies of osteocytes in the lacunae. This structure of bone tissue provides it with the greatest strength.

Cancellous bone

The name "trabecular substance" is also found. If we draw an analogy, the structure is comparable to an ordinary sponge, built from bone plates with cells between them. They are arranged in an orderly manner, in accordance with the distributed functional load. The epiphyses of long bones are mainly built from spongy substance, some are mixed and flat, and all are short. It can be seen that these are mainly light and at the same time strong parts of the human skeleton, which experience loads in different directions. The functions of bone tissue are in direct relationship with its structure, which in this case provides a large area for metabolic processes carried out on it, gives high strength combined with low mass.

Dense (compact) bone substance: what is it?

The diaphyses of the tubular bones consist of a compact substance; in addition, it covers their epiphyses from the outside with a thin plate. It is pierced by narrow channels, through which nerve fibers and blood vessels pass. Some of them are located parallel to the bone surface (central or Haversian). Others emerge on the surface of the bone (nutrient openings), through which arteries and nerves penetrate inward, and veins penetrate outward. The central canal, together with the bone plates surrounding it, forms the so-called Haversian system (osteon). This is the main content of the compact substance and they are considered as its morphofunctional unit.

Osteon is a structural unit of bone tissue

Its second name is the Haversian system. This is a collection of bone plates that look like cylinders inserted into each other, the space between them is filled by osteocytes. In the center is the Haversian canal, through which the blood vessels that ensure metabolism in bone cells pass. Between adjacent structural units there are intercalary (interstitial) plates. In fact, they are the remnants of osteons that existed previously and were destroyed at the moment when the bone tissue underwent restructuring. There are also general and surrounding plates; they form the innermost and outer layers of the compact bone substance, respectively.

Periosteum: structure and significance

Based on the name, we can determine that it covers the outside of the bones. It is attached to them with the help of collagen fibers, collected in thick bundles, which penetrate and intertwine with the outer layer of bone plates. It has two distinct layers:

• external (it is formed by dense fibrous, unformed connective tissue, it is dominated by fibers located parallel to the surface of the bone);
• the inner layer is well defined in children and less noticeable in adults (formed by loose fibrous connective tissue, which contains spindle-shaped flat cells - inactive osteoblasts and their precursors).

The periosteum performs several important functions. Firstly, trophic, that is, it provides the bone with nutrition, since it contains vessels on the surface that penetrate inside along with the nerves through special nutrient openings. These channels feed the bone marrow. Secondly, regenerative. It is explained by the presence of osteogenic cells, which, when stimulated, transform into active osteoblasts that produce matrix and cause the growth of bone tissue, ensuring its regeneration. Thirdly, the mechanical or support function. That is, ensuring the mechanical connection of the bone with other structures attached to it (tendons, muscles and ligaments).

Functions of bone tissue

Among the main functions are the following:

1. Motor, support (biomechanical).
2. Protective. Bones protect the brain, blood vessels and nerves, internal organs, etc. from damage.
3. Hematopoietic: hemo- and lymphopoiesis occurs in the bone marrow.
4. Metabolic function (participation in metabolism).
5. Reparative and regenerative, consisting in the restoration and regeneration of bone tissue.
6. Morph-forming role.
7. Bone tissue is a kind of depot of minerals and growth factors.