The structure of the extracellular matrix (ECM) and intercellular contacts. Intercellular matrix Extracellular matrix

Osteoclasts

Osteocytes

Osteoblasts

BONE CELLS

FUNCTIONS OF BONE TISSUE

LECTURE No.

Topic: Biochemistry of bone tissue

Faculties: Dentistry.

Bone tissue is a type of connective tissue with highly mineralized intercellular substance.

1. Shaping

2. Support (fixation of muscles, internal organs)

3. Protective (chest, skull, etc.)

4. Storage (depot of minerals: calcium, magnesium, phosphorus, sodium, etc.).

5. Regulation of CBS (in case of acidosis it releases Na +, Ca 3 (PO 4) 2)

In the human body, there are 2 types of bone tissue: reticulofibrous (spongy bone substance) and lamellar (compact bone substance). Various types of bones are formed from them: tubular, spongy, etc.

Like any fabric, bone tissue consists of cells and intercellular matrix.

There are 2 types of cells of mesenchymal origin in bone tissue.

1 type:

a) osteogenic stem cells;

b) semi-stem stromal cells;

c) osteoblasts (from which osteocytes are formed);

d) osteocytes;

Type 2:

a) hematopoietic stem cells;

b) semi-stem hematopoietic cells (from which myeloid cells and macrophages are formed);

c) unipotent colony-forming monocyte cell (from it a monoblast → promonocyte → monocyte → osteoclast is formed);

Young, non-dividing cells that create bone tissue. They have different shapes: cubic, pyramidal, angular. Contains 1 core. The broad ER, mitochondria and Golgi complex are well developed in the cytoplasm. There is a lot of RNA in the cell, high alkaline phosphatase activity, and active protein biosynthesis (collagen, proteoglycans, enzymes).

They are found only in the deep layers of the periosteum and in places of bone tissue regeneration. Cover the entire surface of the developing bone beam.

The predominant cells of bone tissue are formed from osteoblasts. They are not capable of division, have a branched shape, a large nucleus in the center of the cell, contain few organelles, and do not have centrioles. They are located in lacunae and produce components of the intercellular substance.

Giant multinucleated cells of hematogenous nature. There are 2 zones in the cell. The cell has many vacuoles, mitochondria, and lysosomes. There are few ribosomes, the rough ER is poorly developed.

Osteoclast activity is regulated by T lymphocytes through cytokines. Osteoclasts are capable of destroying calcified cartilage or bone. They release CO 2 and carbonic anhydrase into the intercellular fluid. H 2 O + CO 2 = H 2 CO 3 The accumulation of acids leads to the destruction of calcium salts and the organic matrix.

The intercellular matrix of bone tissue includes organic and inorganic substances. In compact bone, the inorganic component makes up 70% of the bone mass, the organic component makes up 20% of the bone mass, and water makes up 10% of the bone mass. At the same time, by volume, the inorganic component accounts for only about ¼ of the bone; the rest is occupied by organic components and water.

In spongy bone tissue, the inorganic component makes up 33-40% of the bone mass, the organic component - 50% of the bone mass, and water - 10% of the bone mass.

Organic component of bone tissue consists mainly (90-95%) of collagen fibers (type 1 collagen), which contain a lot of hydroxyproline, lysine, phosphate associated with serine, and little hydroxylysine.

The organic component of bone tissue contains small amounts of proteoglycans and GAGs. The main representative is chondroitin-4-sulfate, some chondroitin-6-sulfate, keratan sulfate, hyaluronic acid.

Bone tissue contains non-collagen structural proteins osteocalcin, osteonectin, osteorontin, etc. Osteonectin is a mediator of calcification; it binds calcium and phosphorus to collagen. Peptide (49AK) containing 3 γ-carboxyglutamic acid residues. Vitamin K is involved in the synthesis of this peptide; it ensures the carboxylation of glutamic acid.

Inert tissue contains enzymes: alkaline phosphatase (a lot in growing bones), acid phosphatase (little), collagenase, pyrophosphatase. Phosphotases release phosphate from organic compounds. Pyrophosphatase breaks down pyrophosphate, which is an inhibitor of calcification.

Also, the organic component is represented by various organic acids, fumaric, malic, lactic, etc. Lipids are present.

Mineral component of bone tissue an adult consists mainly of hydroxyapatite (approximate composition Ca 10 (PO 4) 6 (OH) 2), in addition, it includes calcium phosphates (Ca 3 (PO 4) 2), magnesium (Mg 3 (PO 4) 2) , carbonates, fluorides, hydroxides, citrates (1%), etc. The composition of bones includes most of the Mg 2+, about a quarter of Na + and a small part of the K + contained in the body. In young children, amorphous calcium phosphate (Ca 3 (PO 4) 2) predominates in the mineral component of bone tissue; it is a labile reserve of calcium and phosphorus.

Hydroxyapatite crystals have the shape of plates or rods, about 8-15Å thick, 20-40Å wide, 200-400Å long. In the crystal lattice of hydroxyapatite, Ca 2+ can be replaced by other divalent cations. Heavy metal ions can be introduced into the growing crystal lattice of hydroxyapatite: lead, radium, uranium and heavy elements formed during the decay of uranium, such as strontium.

Anions other than phosphate and hydroxyl are either adsorbed onto the large surface area formed by the small crystals or dissolved in the hydration shell of the crystal lattice. Na + ions are adsorbed on the surface of the crystals.

Hydroxyapatite crystals are connected to each other through Ca 2+ using γ-carboxyglutamic acid residues of the peptide (49 AA).

Due to the crystalline structure formed by organic and inorganic components, the elastic modulus of bone is similar to concrete.

5030 0

Mast cells are mysterious

This is more of a general purpose special forces. It has many names: labrocyte (Greek labros huge + hist. cytus cell), mastocyte (German mastig fat + hist. cytus cell), heparinocyte (heparin-secreting cell). These cells are mysterious and amazing. Mast cells are present wherever there is at least a minimal layer of connective tissue. They are distinguished by their diverse appearance (polymorphism). It is not yet known exactly from which progenitor cells mast cells are formed. There is more evidence that these are blood monocytes.

Surprisingly, many doctors with advanced degrees are completely unaware of the existence of mast cells and their functions. Endocrinologists are especially famous for this, believing that all control of the body is carried out from a limited set of endocrine organs (“the fact of varicose veins has nothing to do with endocrinology” - from the RMS forum). The mast cell produces about a hundred different hormones and mediators (hyaluronic acid, histamine, serotonin, heparin, etc.) and makes up 50% of all connective tissue cells.

Acupuncturists give mast cells an important role in encoding the information received by the acupuncture point. It is believed that activation of the functional activity of mast cells leads to the release into the pericellular fluid of physiologically active substances - mediators of pain or inflammation: substance P, bradykinin, histamine, serotonin, etc., acting on surrounding cells and on receptors of nerve endings, where the received information is encoded and transmitted further along the nervous path.

Labrocytes are most often localized near small vessels (capillaries), under the epithelium and near the glands of the skin, mucous and serous membranes, in the capsule and trabeculae of parenchymal (kidneys, liver) organs, and in lymphoid organs.

Heparin, histamine, serotonin, dopamine, chondroitin sulfates, hyaluronic acid, glycoproteins, phospholipids, chemotactic factors and platelet activating factor were found in mast cell granules. The granules of mast cells include enzymes - lipase, esterase, tryptase (activating kininogen), enzymes of the Krebs cycle, anaerobic glycolysis and pentose cycle.

Intercellular substance (matrix) is omnipresent

The intercellular substance (sometimes called the matrix) performs a variety of functions. It provides contacts between cells (mediator), forms mechanically strong structures such as bones, cartilage, tendons and joints (builder), forms the basis of filtering membranes, for example in the kidneys (founder), insulates cells and tissues from each other, e.g. , provides gliding in joints and cell movement (helper), forms cell migration paths along which they can move, for example, during embryonic development (conductor).

Thus, the intercellular substance is extremely diverse both in chemical composition and in the functions it performs. Since the extracellular connective tissue space forms a functional unity with the cell, the cell can respond to stimulation only when information comes to it from the intercellular space. The dynamic structure of this space and the principles of its regulation (the system of basic regulation) determine the effectiveness of extra- and intracellular catalytic processes.

And they depend on the structure of the main substance (also called the matrix or extracellular matrix). The matrix is ​​a molecular lattice consisting of highly polymeric carbohydrates and proteins (proteoglycans-glycosaminoglycans), structural proteins (collagen, elastin) and connecting glycoproteins (fibronectin). Proteoglycan/glycosaminoglycan complexes have a negative electrical charge and are capable of binding water and participating in ion exchange.

Autonomic nerve fibers ending in the matrix provide connection to the central nervous system, and the capillary bed to the endocrine system.

Proteoglycans and glycoaminoglycans are the rulers

The cellular and fibrous elements of connective tissue are immersed in the ground substance, the main chemical components of which are proteins and polysaccharides. The latter do not exist in free form in tissues. They are attached by covalent bonds to proteins and therefore such compounds are called proteoglycans (PG). The structure of the proteoglycan resembles a bottle brush.

HA - hyaluronic acid; SB - binding protein; BS - protein core of proteoglycan unit; CS - chondroitin sulfate chains; KS - keratan sulfate chains.

In the center is a long linear molecule of hyaluronic acid. About 70-100 units of proteoglycans (protein rods) are attached with the help of a holding protein. They contain chondroitin sulfate and keratan sulfate. The biosynthesis of proteoglycans is mainly carried out in fibroblasts (chondroblasts, osteoblasts). It is proteoglycans that ensure the transport of water, salts, amino acids and lipids in avascular tissues - cartilage, vessel wall, cornea, heart valves.

Scheme of basic regulation. Relationships between capillaries, lymphatic vessels, ground substance, terminal vegetative axons, connective tissue cells (mast cells, immunocompetent cells, fibroblasts, etc.) and parenchyma cells of organs. Epithelial and endothelial cell complexes are located under the basement membrane, communicating with the ground substance. On the surface of all cells there is a layer connected to the main substance, a glycoprotein or lipid membrane, and histocompatibility complexes are located here. The main substance is functionally connected through the capillary bed to the endocrine system, and through axons to the central nervous system. Fibroblast is the center of metabolic processes

A.A. Alekseev, N.V. Zavorotinskaya

SCIENCE

Intercellular matrix theory

We all know that the human body consists of cells, but few people think that their number is approximately 20% of the entire body. The remaining 80% consists of “intercellular matrix”. What is the “intercellular matrix”? How can you see it?

The most obvious example of an intercellular matrix in the human body is bone tissue.

The cellular basis of bone tissue is Osteoblast. These are cells 5-7 microns in size that build bone tissue. Their number is even less by weight than 20%. Human bone is composed of crystals of hydroxyapatite, collagen(type I), etc. Everything else is the intercellular matrix.

Theory of human aging

Even if the cells are 100% healthy, in old age the destruction of the intercellular matrix occurs first. As a result, the skin becomes flabby, the intercellular matrix is ​​destroyed, the skin “hangs”, and we see all the signs of skin aging with the naked eye. We can see the same thing in the example of bones. People do not get sick because their cells behave “wrong.” Osteoporosis causes bones to become brittle, primarily due to the destruction of the intercellular matrix.

The same problems arise with baldness. There are no cells in human hair; on the contrary, hair consists of cell waste products, and this is the intercellular matrix in its pure form. When the intercellular matrix is ​​destroyed, our hair falls out.

THE FOLLOWING FACTS SAY IN FAVOR OF THIS THEORY:

Let's take structure restoration as an example, or the process of regeneration.

For example, a person cut himself. Cell restoration occurs at approximately the same speed in a child as in an elderly person. The difference in the rate of healing of wounds is calculated in percentages, but not by an order of magnitude. In older people, wounds heal just as quickly, at a comparable rate, as in young people. If a young person’s shallow cut heals within a week, then for an elderly person it takes 8-10 days. The difference is not dramatic; cells divide and regenerate at approximately the same rate throughout a person’s life, if he is healthy. This indicates that the cells are in order, and with age they do not lose their ability to regenerate and divide.

For many years, it was a big mystery for the world's leading scientists - how do cells actually get nourished? It has long been clear to everyone that all nutrients penetrate into cells with the blood through blood vessels, through capillaries. What next? If you take a microscope and look at your cells, you will find that capillaries do not go to every cell in your body, but rather supply oxygen and nutrients to very large groups of cells. What's next?

The intercellular matrix has a very complex structure. In the intercellular matrix, paths are formed for the transport of useful substances and the removal of waste products, and these paths do not always exist, and depending on the time of day, a person’s condition, they can form in the form of “tunnels”, highways, etc. They can form in the same place. It's like the analogy of reversible lanes on roads, where people drive in one direction in the morning and in the opposite direction in the evening.

THE STRUCTURE OF THE INTERCELLULAR MATRIX IS NOT COMPLETELY KNOWN.

But it has been absolutely clearly proven: the intercellular matrix consists of several main components. It is generally accepted in the scientific community that the main component of the intercellular matrix is ​​hyaluronic acid. Therefore, it is now very fashionable, widely used in cosmetic creams, dietary supplements, etc. In addition, it contains collagen or amorphous protein, chondroitin, in particular chondroitin sulfate, which is especially abundant in joints. And besides this, recent research shows that the most important element is silica. It forms a primary structure, which consists of silicon compounds (SiO2). Very reminiscent of the lines from the Bible, when “God created man from clay,” and clay, as we know, consists of silica, silicon oxide.

Although the amount of silicon in the tissues of the human body is not large (only 2%), it plays a huge role. Despite the fact that there is a lot of silicon in nature - it is the main element in the earth's crust, there is very little bioavailable silicon. Ordinary silica (sand, dust, earth) is a very chemically inert substance that does not enter into chemical reactions. There seems to be a lot of it, but the body has practically nowhere to take it.

Intercellular matrix is a supramolecular complex formed by a complex network of interconnected macromolecules.

In the body, the intercellular matrix forms such highly specialized structures as cartilage, tendons, basement membranes, and also (with secondary deposition of calcium phosphate) bones and teeth. These structures differ from each other both in molecular composition and in the ways of organizing the main components (proteins and polysaccharides) in various forms of the intercellular matrix.

Chemical composition of the intercellular matrix

The composition of the intercellular matrix includes: 1). Collagen And elastin fibers . They give the fabric mechanical strength, preventing it from stretching; 2). amorphous substance in the form of GAGs and proteoglycans. It retains water and minerals and prevents tissue compression; 3). non-collagenous structural proteins - fibronectin, laminin, tenascin, osteonectin, etc. In addition, it may be present in the intercellular matrix mineral component - in bones and teeth: hydroxyapatite, calcium, magnesium phosphates, etc. It gives mechanical strength to bones, teeth, and creates a reserve of calcium, magnesium, sodium, and phosphorus in the body.

Function of the intercellular matrix

The intercellular matrix performs various functions in the body:

· forms the framework of organs and tissues;

· is a universal “biological” glue;

· participates in the regulation of water-salt metabolism;

· forms highly specialized structures (bones, teeth, cartilage, tendons, basement membranes).

· surrounding cells, influences their attachment, development, proliferation, organization and metabolism.

COLLAGEN

Collagen- fibrillar protein, the main structural component of the intercellular matrix. Collagen has enormous strength (Collagen is stronger than steel wire of the same cross-section; it can withstand a load 10,000 times its own weight) and is practically inextensible. It is the most abundant protein in the body, accounting for 25 to 33% of the total amount of protein in the body, i.e. 6% body weight. About 50% of all collagen proteins are found in skeletal tissues, about 40% in the skin and 10% in the stroma of internal organs.

The structure of collagen

Collagen refers to two substances: tropocollagen and procollagen.

Molecule tropocollagen consists of 3 α-chains. About 30 types of α-chains are known, differing in amino acid composition. Most α-chains contain about 1000 AA. Tropocollagen contains 33% glycine, 25% proline and 4-hydroxyproline, 11% alanine, hydroxylysine, little histidine, methionine and tyrosine, no cysteine ​​and tryptophan.

· The primary structure of α-chains consists of a repeating amino acid sequence: Glycine-X-Y . IN X the position most often contains proline, and in Y– 4-hydroxyproline or 5-hydroxylysine.

· The spatial structure of the α-chain is represented by a left-handed helix in which there are 3 AA per turn.

3 α-chains twist together into a right-handed superhelix tropocollagen . It is stabilized by hydrogen bonds, and the AA radicals are directed outward.

Molecule procollagen structured in the same way as tropocollagen, but at its ends there are C- and N-propeptides, forming globules. The N-terminal propeptide consists of 100 AA, the C-terminal propeptide consists of 250 AA. C- and N-Proteopeptides contain cysteine, which forms a globular structure through disulfide bridges.

Types of collagen

Collagen is a polymorphic protein; currently 19 types of collagen are known, which differ from each other in the primary structure of peptide chains, functions and localization in the body. 95% of all collagen in the human body is collagen types I, II and III.

Types	Genes	Tissues and organs
I	COLIA1, COL1A2	Skin, tendons, bones, cornea, placenta, arteries, liver, dentin
II	COL2A1	Cartilage, intervertebral discs, vitreous body, cornea
III	C0L3A1	Arteries, uterus, fetal skin, stroma of parenchymal organs
IV	COL4A1-COL4A6	Basement membranes
V	COL5A1-COL5A3	Minor component of tissues containing collagen types I and II (skin, cornea, bones, cartilage, intervertebral discs, placenta)
VI	COL6A1-COL6A3	Cartilage, blood vessels, ligaments, skin, uterus, lungs, kidneys
VII	COL7A1	Amnion, skin, esophagus, cornea, chorion
VIII	COL8A1-COL8A2	Cornea, blood vessels, endothelial culture medium
IX	COL9A1-COL9A3
X	COL10A1	Cartilages (hypertrophied)
XI	COLUA1-COL11A2	Tissues containing type II collagen (cartilage, intervertebral discs, vitreous body)
XII	COL12A1
XIII	C0L13A1	Many fabrics
XIV	COL14A1	Tissues containing type I collagen (skin, bones, tendons, etc.)
XV	C0L15A1	Many fabrics
XVI	COL16A1	Many fabrics
XVII	COL17A1	Skin hemidesmosomes
XVIII	COL18A1	Many tissues, e.g. liver, kidneys
XIX	COL19A1	Rhabdomyosarcoma cells

Collagen genes are named by collagen type and written in Arabic numerals, for example COL1 - type 1 collagen gene, COL2 - type II collagen gene, etc. The letter A (denotes the α-chain) and an Arabic numeral (denotes the type of α-chain) are assigned to this symbol. For example, COL1A1 and COL1A2 encode, respectively, the α 1 and α 2 chains of type I collagen.