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 has high mechanical qualities, its strength can be compared with the strength of metal. Chemical composition living human bone contains: 50% water, 12.5% ​​organic substances of protein nature (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 dynamic reactive system, changing 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 the 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.

Bone tissue is distinguished by a number of very unique qualities that sharply distinguish it from all other tissues and systems. human body and placing it in a separate place. The main and main feature of bone tissue is its richness in mineral salts.

If we take the body weight of an adult as an average of 70 kg, then the bone skeleton weighs 7 kg, and together with the bone marrow - 10 kg (muscles - “meat” - weigh 30 kg). The bones themselves, by weight, are 25% water, 30% organic matter and 45% minerals. The water content and therefore the relative content of other ingredients varies. The amount of water is comparatively very large in embryonic life, it decreases in childhood and gradually decreases with the growth and development of the child, adolescent and mature person, reaching in old age the smallest ratio to total weight. With age, bones literally dry out.

The organic composition of bones is formed mainly from proteins - proteins, mainly ossein, but the complex organic part of bone tissue also includes some albumins, mucoids and other substances of a very complex chemical structure.

What is the mineral composition of bone matter that interests us most? 85% of the salts are lime phosphate, 10.5% calcium carbonate, 1.5% magnesium phosphate, and the remaining 3% are sodium, potassium, chlorine and some elements rare for the human body. Calcium phosphate, therefore constituting 19/20 of the contents of the total salty bone matter, forms 58% of the total weight of the bones.

Phosphoric acid salts have a crystalline structure, and the crystals are located in the bone correctly and naturally. A very thorough study of the mineral skeleton of bone matter, carried out in the 30s using the most advanced methods, primarily through x-ray structural analysis, showed that inorganic human bone matter has the structure of phosphatite-apatite, namely hydroxyl-apatite. It is interesting that the apatite in human bones (and teeth) is close or even similar to the natural mineral apatite in dead nature. This identity of apatite of human bone and mining origin is also indicated by their comparative study in polarized light. Human bone apatite is also distinguished by the content of a small amount of chlorine or fluorine halogen. Some specialists structural analysis stand on the point of view that in human bones apatite is still associated with other chemical compounds, i.e. that crystals of inorganic bone substance are a mixture of two inorganic chemical substances, one of which is close to apatite. It is believed that the most correct physical and chemical structure of bone apatite was deciphered by the Hungarian scientist St. Naray-Szabo. The most probable formula for the structure of the inorganic composition of bone is: ZSA 3 (PO 4) 2. CaX 2, where X is either Cl, F, OH, V2O, 1/2 SO 4, 1/2 CO 3, etc. There are also indications that apatite consists of two molecules - CaF. Ca 4 (PO 4) 3 or CaC1. Ca 4 (PO 4) 3.

Extremely interesting are the indications of Reynolds et al. that during certain pathological processes bones lose their normal chemical apatite structure. This occurs, for example, in hyperparathyroid osteodystrophy (Recklinghausen's disease), while in Paget's disease the apatite crystal structure is completely preserved.

Bone tissue is, albeit very ancient in phylogeny, but at the same time highly developed and extremely finely and in detail differentiated, extremely complex in all its life manifestations mesenchymal connective tissue.

Changes in bones during various pathological processes are infinitely diverse; for each individual disease, in each individual bone, in each individual case, the pathoanatomical and pathophysiological, and therefore the x-ray picture, has its own characteristics. All this enormous variety of painful phenomena is reduced, however, in the end only to some not so numerous elementary qualitative and quantitative processes.

A disease, as is known, is not only a perverted arithmetic sum of individual normal phenomena; under pathological conditions, specific qualitative changes arise in the whole organism and in individual organs and tissues, for which there are no normal prototypes. Painfully altered bone also undergoes deep qualitative metamorphosis. The periosteum, for example, forming a callus at the site of a diaphyseal fracture, begins to perform a new function that is not normally characteristic of it, it produces cartilage tissue. A bone tumor is associated with the development, for example, of epithelial, myxomatous, giant cell and other formations that are as foreign to normal bone histologically as deposits of cholesterol in xanthomatosis or kerasin in Gaucher disease are chemically unusual for it. The bone apparatus during rickets or Paget's restructuring acquires completely new physical, chemical, biological and other qualities for which in normal bone we are not able to find quantitative criteria for comparison.

But these qualitative properties, specific to pathological processes in the bone substance, unfortunately, cannot themselves be directly determined radiographically; they appear on radiographs only in the form of indirect, secondary symptoms. The power of radiology does not lie in recognizing and studying them. Only when the qualitatively changed tissue in its quantitative definition has reached the level of possible detection does the x-ray method of research come into its own. With the help of impeccable experimental research Polina Mack proved that 95% of the various components of bone tissue absorb X-rays due to mineral composition(80% of the rays are blocked by calcium and 15% by phosphorus), and only up to 5% of the shadow image of bones is due to the organic “soft” ingredient of bone tissue. Therefore, due to the very nature of X-ray examination, in the X-ray diagnosis of diseases of bones and joints, the assessment of quantitative changes in bone tissue comes to the fore. You cannot measure distance with scales. The radiologist, using his extremely valuable, but still one-sided method, is currently still forced to limit himself to the analysis of mainly two main quantitative processes of bone activity, namely the creation of bone and its destruction.

Bones occupy a strictly defined place in the human body. Like any organ, bone is represented different types tissues, the main place among which is occupied by bone tissue, which is a type of connective tissue.

Bone(os) has a complex structure and chemical composition. In a living organism, the bones of an adult human contain up to 50% water, 28.15% organic and 21.85% inorganic substances. Inorganic substances are represented by compounds of calcium, phosphorus, magnesium and other elements. Macerated bone consists of 1/3 of organic substances, called “ossein,” and 2/3 of inorganic substances.

The strength of bone is ensured by the physicochemical unity of inorganic and organic substances and the features of its design. The predominance of organic substances provides significant elasticity and elasticity of the bone. With an increase in the proportion of inorganic compounds (in old age, in some diseases), the bone becomes brittle and brittle. The ratio of inorganic substances in the composition of bone in different people not the same. Even in the same person it changes throughout life, depending on dietary habits, professional activity, heredity, environmental conditions, etc.

Most adult bones are composed of lamellar bone tissue. It forms a compact and spongy substance, the distribution of which depends on the functional loads on the bone.

The compact substance (substantia compacta) of the bone forms the diaphysis of the tubular bones, in the form of a thin plate it covers the outside of their epiphyses, as well as spongy and flat bones built from spongy substance. The compact substance of the bone is penetrated by thin channels in which blood vessels and nerve fibers pass. Some channels are located predominantly parallel to the surface of the bone (central, or Haversian, channels), others open on the surface of the bone with nutrient openings (foramina nutricia), through which arteries and nerves penetrate into the thickness of the bone, and veins emerge.

The walls of the central (Haversian) canals (canales centrales) are formed by concentric plates 4-15 microns thick, as if inserted into each other. Around one canal there are from 4 to 20 such bone plates. The central canal, together with the surrounding plates, is called an osteon. (Haversian system). Osteon is a structural and functional unit of compact bone substance. The spaces between osteons are filled insert plates. The outer layer of the compact substance is formed outer surrounding plates, being a product of the bone-forming function of the periosteum. The inner layer delimiting the bone marrow cavity is represented by inner surrounding plates, formed from osteogenic endosteal cells.

Spongy (trabecular) bone substance (substantia spongiosa) resembles a sponge built from bone plates (beams) with cells between them. The location and size of the bone beams are determined by the loads that the bone experiences in the form of tension and compression. The lines corresponding to the orientation of the bone beams are called compression and tension curves. The location of the bone beams at an angle to each other promotes uniform transmission of pressure (muscle traction) to the bone. This design gives the bone strength with the least amount of bone material required.

The entire bone, except its articular surfaces, is covered with a connective tissue membrane - the periosteum. The periosteum (periosteum) firmly fuses with the bone due to connective tissue perforating (Sharpey's) fibers penetrating deep into the bone. The periosteum has two layers. Outer fibrous layer formed by collagen fibers, which give special strength to the periosteum. It contains blood vessels and nerves. Inner layer - germinal, cambial. It is adjacent directly to the outer surface of the bone and contains osteogenic cells, due to which the bone grows in thickness and regenerates after damage. Thus, the periosteum performs not only protective and trophic, but also bone-forming functions.

From the inside, from the side of the bone marrow cavities, the bone is covered with endosteum. The endoste, in the form of a thin plate, is tightly adjacent to the inner surface of the bone and also performs an osteogenic function.

Bones are characterized by significant plasticity. They are easily rebuilt under the influence of training and physical activity, which is manifested in an increase or decrease in the number of osteons, changes in the thickness of the bone plates of the compact and spongy substances. For optimal bone development, moderate, regular exercise is preferred. physical exercise. A sedentary lifestyle and low loads contribute to weakening and thinning of bones. The bone acquires a coarse structure and even partially resolves (bone resorption, osteoporosis). Occupation also affects the structure of the bone. In addition to environmental factors, hereditary and sexual factors also play a significant role.

The plasticity of bone tissue and its active restructuring are caused by the formation of new bone cells and intercellular substance against the background of destruction (resorption) of existing bone tissue. Resorption is ensured by the activity of osteoclasts. In place of the collapsing bone, new bone beams and new osteons are formed.

The composition of fresh adult human bone includes water - 50%, fat - 16%, other organic substances - 12%, inorganic substances - 22%.

Defatted and dried bones contain approximately 2/3 inorganic and 1/3 organic matter. In addition, bones contain vitamins A, D and C.

Organic matter of bone tissue - ossein– gives them elasticity. It dissolves when boiled in water, forming bone glue. Inorganic bone matter is represented mainly by calcium salts, which with a small admixture of other mineral substances form hydroxyapatite crystals.

The combination of organic and inorganic substances determines the strength and lightness of bone tissue. So, with a low specific gravity of 1.87, i.e. not twice the specific gravity of water, the strength of bone exceeds the strength of granite. The femur, for example, when compressed along the longitudinal axis, can withstand loads of over 1500 kg. If a bone is fired, the organic substance burns out, but the inorganic substance remains and retains the shape of the bone and its hardness, but such a bone becomes very fragile and crumbles when pressed. On the contrary, after soaking in a solution of acids, as a result of which the mineral salts dissolve and the organic matter remains, the bone also retains its shape, but becomes so elastic that it can be tied into a knot. Consequently, the elasticity of the bone depends on ossein, and its hardness - on mineral substances.

The chemical composition of bones is related to age, functional load, and general condition of the body. The greater the load on the bone, the more inorganic substances there are. For example, the femur and lumbar vertebrae contain the largest amount of calcium carbonate. With increasing age, the amount of organic substances decreases, and inorganic substances increase. In young children there is comparatively more ossein; accordingly, the bones are highly flexible and therefore rarely break. On the contrary, in old age the ratio of organic and inorganic substances changes in favor of the latter. Bones become less elastic and more fragile, as a result of which bone fractures are most often observed in old people.

Classification of bones

Based on shape, function and development, bones are divided into three parts: tubular, spongy, mixed.

Tubular bones are part of the skeleton of the limbs, playing the role of levers in those parts of the body where large-scale movements predominate. Tubular bones are divided into long– humerus, forearm bones, femur, shin bones and short– bones of the metacarpus, metatarsus and phalanges of the fingers. Tubular bones are characterized by the presence of a middle part - diaphysis, containing a cavity (marrow cavity), and two expanded ends - epiphyses. One of the epiphyses is located closer to the body - proximal, the other is further from him – distal. The section of tubular bone located between the diaphysis and epiphysis is called metaphysis. The bone processes that serve to attach muscles are called apophyses.

Spongy bones are located in those parts of the skeleton where it is necessary to provide sufficient strength and support with a small range of movements. Among the spongy bones there are long(ribs, sternum), short(vertebrae, carpal bones, tarsus) and flat(skull bones, belt bones). Spongy bones include sesamoid bones (patella, pisiform bone, sesamoid bones of the fingers and toes). They are located near the joints, are not directly connected to the bones of the skeleton and develop in the thickness of the muscle tendons. The presence of these bones helps to increase the muscle's leverage and therefore increase its torque.

Mixed dice– this includes bones that merge from several parts that have different functions, structure and development (bones of the base of the skull).

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 as part of the inner layer of periosteum, covering the surface of the bone from the outside - the periosteum, as well as as part of the endosteum, lining the contours of all internal bone cavities, 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 significant amount 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 secrete into environment collagen fibrils, proteoglycans and glycosaminoglycans. 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. Minerals, located as part of the main substance in the organic matrix of bones, 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).

From total number 10% of non-collagen proteins 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.

Bone tissue also contains hyaluronic acid. 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

Protein

Properties and Functions

Osteonectin

Glycophosphoprotein capable of binding Ca 2+

Alkaline phosphatase

Removes phosphate from organic compounds at alkaline pH values

Thrombospondin

Protein with mol. weighing 145 kDa, consisting of three identical subunits linked to each other by disulfide bonds. Each subunit has several different domains that give the protein the ability to bind to other bone matrix proteins - heparan-containing proteoglycans, fibronectin, laminin, collagen types I and V, and osteonectin. The N-terminal region of thrombospondin contains a sequence of amino acids that ensures cell attachment. The binding of thrombospondin to receptors on the cell surface is affected by the Ca 2+ concentration. In bone tissue, thrombospondin is synthesized by osteoblasts

Fibronectin

Binds to cell surfaces, fibrin, heparin, bacteria, collagen. In bone tissue, fibronectin is synthesized in the early stages of osteogenesis and is stored in the mineralized matrix

Osteopontin

Glycophosphoprotein containing N- and O-linked oligosaccharides; participates in cell adhesion

Bone acidic glycoprotein-75

Protein with mol. weighing 75 kDa, contains sialic acids and phosphate residues. Capable of binding Ca 2+ ions, inherent in bone, dentin and cartilaginous growth plate. Inhibits bone resorption processes

Bone sialoprotein

Adhesive glycoprotein containing up to 50% carbohydrates

Matrix Gla protein

Protein containing 5 residues of 7-carboxyglutamic acid; capable of binding to hydroxyapatite. Appears in the early stages of bone tissue development; the protein is also found in the lungs, heart, kidneys, cartilage

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 maximum speed loss of bone tissue, which reaches 2-5% per year and continues at this rate until 60-70 years. As a result, women lose from 30 to 50% of 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 a 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, a protein with a molecular weight of 16 kDa, is formed primarily in adipocytes and exerts its action through increased synthesis of cytokines, epithelial and keratinocyte growth factors.

Rice. 5.5.Bone tissue remodeling.

Active secreting osteoblasts create layers of osteoid, the unmineralized 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. Formation of mineral crystal lattice begins in the zone located between 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. Calcitonin secretion 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 through 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 into 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-collagenous 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 effect 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. If there is a shortage 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, the cause of which is 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 children early age is accompanied by a decrease in the blood content of osteocalcin and the degree of decrease in its concentration depends on the severity of the rachitic 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 as special case 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 (most rare view), 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.