DENS-CONNECTIVE TISSUE
FUNCTIONS AND COMPOSITION OF DENS - CONNECTIVE TISSUE ( DCT )
DCT serves a variety of functions. Its most obvious function is to provide and maintain body structure. Additionally, DCT plays important roles in providing a defense and immunologic response to invading antigens. There is also an association between blood capillaries and DCT for the transport of nutrients and removal of metabolic wastes.
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By definition, DCT consists of an intricate extracellular matrix in contact with various cells and protein fibers. DCT structures differ considerably in appearance, consistency, and composition in different regions of the body according to the local functional requirements. These differences are related to the character of the extracellular matrix, the predominance of cell types, as well as the concentration, arrangement, and types of fibers.
What are the types of Dens-Connective Tissue ?
DCT is classified by the degree of orientation in fibrous elements into irregular and regular types. The connective tissue sheaths of individual muscles (intermuscular septa) and synovial tendon sheaths are classified as dense irregular connective tissue. As the name implies, the connective tissue fibers are densely arranged, but in an irregular, more random fashion. In comparison, dense regular connective tissue includes those highly fibrous tissues with fibers regularly oriented to form either connective tissue sheets (such as aponeuroses and fasciae) or thicker bundles (such as ligaments or tendons). Other examples of dense regular connective tissue include the deep fascia of the lower extremity, the fascia lata of the thigh with its lateral iliotibial band, and crural fascia with its thickened retinacula.
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Extracellular Matrix:
The extracellular matrix (ECM), or ground substance, is an amorphous gel-like material occupying the interstitial space between the DCT cells and fibers. It is composed of a mixture of water and organic macromolecules interwoven with three major fiber-forming proteins elastin, reticulin, and collagen. These macromolecules are secreted by fibroblasts.
Importantly, the ECM holds the connective tissue cells together and influences the development, shape, proliferation, migration, and metabolic functions of the cells that contact it. The matrix has enormous water binding properties and fibrous proteins. The complex interaction among the ECM, cells, and fibers results in the formation of highly specialized connective tissue structures, such as basal lamina, bone, cartilage, ligaments, and tendons.
and acts as a lubricant for movement of adjacent fibers.
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Glycosaminoglycans:
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are a product of fibroblast metabolism. They are composed of repeating disaccharide units. One of the two sugar residues in the repeating disaccharide is always an amino acid, hence the Name GAGs are highly negatively charged because of the presence of sulfate and/or carboxyl groups on many of the sugar residues. Enhanced by their high density of negative charges that attract osmotically active cations.
Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are a product of fibroblast metabolism. They are composed of repeating disaccharide units. One of the two sugar residues in the repeating disaccharide is always an amino acid, hence the Name GAGs are highly negatively charged because of the presence of sulfate and/or carboxyl groups on many of the sugar residues. Enhanced by their high density of negative charges that attract osmotically active cations.
What is the function of glycoaminoglycans ?
GAGs are hydrophilic, attracting large amounts of water. Because of the porous and hydrated organization, GAGs allow rapid diffusion of water-soluble molecules and the migration of cells and cell processes.
GAGs interact electrostatically with collagen fibers, binding them together, and thus contributing to their aggregation and strength. The distinctive form in collagen fascicles is thought to be the result of the attachment of GAGs to the collagen fibers. Seven groups of GAGs have been identified by their sugar residues, the type of linkage between their residues, and the number and location of sulfate groups. The particular type and distribution of GAGs in various tissues is demonstrated.
GAGs interact electrostatically with collagen fibers, binding them together, and thus contributing to their aggregation and strength. The distinctive form in collagen fascicles is thought to be the result of the attachment of GAGs to the collagen fibers. Seven groups of GAGs have been identified by their sugar residues, the type of linkage between their residues, and the number and location of sulfate groups. The particular type and distribution of GAGs in various tissues is demonstrated.
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Hyaluronan or hyaluronic acid (HA) is common in cartilage and is thought to be responsible for cohesion within the collagen fibril, enabling the tissue to bear mechanical stresses without distortion. HA exists as a very long carbohydrate chain of thousands of sugar residues, but it is not a typical GAG because it is not covalently linked to a protein core and none of the sugars is sulfated.
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What is the role of hyaluronic acid ?
HA has a special function supporting cell migration in DCT wound healing. Evidence suggests that increased local production of HA, which attracts water and therefore swells the matrix, may be one strategy used to facilitate cell migration during DCT repair.
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TYPE DISTRIBUTION
Hyaluronan (HA) > Connective tissue, skin, cartilage, vitreous body, synovial fluid.
Chondroitin 4-sulfate > Cartilage, bone, skin, arteries, cornea.
Chondroitin 6-sulfate > Bone, skin, arteries, cornea.
Dermatan sulfate > Dermis, tendon, ligament, cartilage, skin, blood vessels, heart valves.
Heparan sulfate > Lung, arteries, cell surfaces.
Heparan > Mast cells, skin, liver, lung.
Keratan sulfate> Cartilage, intervertebral disc, cornea.
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Proteoglycans:
Except for hyaluronan, GAGs covalently bind to protein chains in the ECM to form proteoglycans (PGs). PGs contain 90 to 95% carbohydrate by weight in the form of many long, unbranched GAG chains. They differ significantly in protein content, molecular size, and number and types of GAG chains per molecule. Each type of connective tissue, therefore, has unique PGs in various proportions. The role of PGs is to regulate collagen fibrillogenesis and accelerate polymerization of collagen monomers.21 PGs are ordered in pattern, crossing the collagen fibrils at intervals of 67 nm, which is the same periodicity as that of the intrinsic cross-banding pattern of the collagen fibrils.
Examples of true PGs include:
Except for hyaluronan, GAGs covalently bind to protein chains in the ECM to form proteoglycans (PGs). PGs contain 90 to 95% carbohydrate by weight in the form of many long, unbranched GAG chains. They differ significantly in protein content, molecular size, and number and types of GAG chains per molecule. Each type of connective tissue, therefore, has unique PGs in various proportions. The role of PGs is to regulate collagen fibrillogenesis and accelerate polymerization of collagen monomers.21 PGs are ordered in pattern, crossing the collagen fibrils at intervals of 67 nm, which is the same periodicity as that of the intrinsic cross-banding pattern of the collagen fibrils.
Examples of true PGs include:
aggrecan, biglycan, decorin, perlecan, syndecan, and versican. These PGs have varied roles in the design and maintenance of DCT. Specific functions of PGs are to contribute to the mechanical stability of DCT by resisting compressive and tensional forces as well as most understood PG is aggrecan. It is the predominant PG in articular cartilage and plays an important role in normal joint function.
The percentage of PGs varies directly with the amount of stress or mechanical load placed on the DCT. For example, in tissues that resist tension, such as tendons and ligaments, PGs are in small concentrations (approximately 0.2% of dry weight). Articular cartilage, a tissue subjected to high compressive forces, has a relatively high percentage of PGs (approximately 8 to 10% of dry weight).
CLINICAL CONSIDERATIONS:
Extracellular viability depends on motion. GAGs and PGs have half-lives of 1.7 to 7 days, and motion is required for ECM production. Early on, motion at the level of the DCT might imply gentle isometric contractions rather than gross osteokinematic movements. The forces generated by gentle isometric contractions are often sufficient to keep the DCT lubricated during the phase of recovery in which pain-induced splinting occurs. The absence of both weight bearing and movement can result in a large loss (up to 40%) of PGs in a short period (1 month). Therefore, it is important to maintain some minimal level of joint motion during the early stages of DCT repair and healing.
Glycoproteins:
Structural glycoproteins make up a small but significant proportion of the ECM. They are organic macromolecules containing a protein core to which small, complex, nonrepeating sequences of sugar molecules covalently attach. Glycoproteins usually contain only 1 to 6% carbohydrate by weight and thus are smaller than PGs. Unlike PGs, the protein core predominates. Glycoproteins transport and exchange materials between DCT cells and their environment. Although they do not have a significant mechanical function in DCT, glycoproteins play an important role in the interaction between the cells and their adhesion to collagen. They are thought to enhance cell motility and stimulate cell proliferation.
The percentage of PGs varies directly with the amount of stress or mechanical load placed on the DCT. For example, in tissues that resist tension, such as tendons and ligaments, PGs are in small concentrations (approximately 0.2% of dry weight). Articular cartilage, a tissue subjected to high compressive forces, has a relatively high percentage of PGs (approximately 8 to 10% of dry weight).
CLINICAL CONSIDERATIONS:
Extracellular viability depends on motion. GAGs and PGs have half-lives of 1.7 to 7 days, and motion is required for ECM production. Early on, motion at the level of the DCT might imply gentle isometric contractions rather than gross osteokinematic movements. The forces generated by gentle isometric contractions are often sufficient to keep the DCT lubricated during the phase of recovery in which pain-induced splinting occurs. The absence of both weight bearing and movement can result in a large loss (up to 40%) of PGs in a short period (1 month). Therefore, it is important to maintain some minimal level of joint motion during the early stages of DCT repair and healing.
Glycoproteins:
Structural glycoproteins make up a small but significant proportion of the ECM. They are organic macromolecules containing a protein core to which small, complex, nonrepeating sequences of sugar molecules covalently attach. Glycoproteins usually contain only 1 to 6% carbohydrate by weight and thus are smaller than PGs. Unlike PGs, the protein core predominates. Glycoproteins transport and exchange materials between DCT cells and their environment. Although they do not have a significant mechanical function in DCT, glycoproteins play an important role in the interaction between the cells and their adhesion to collagen. They are thought to enhance cell motility and stimulate cell proliferation.
Types of glycoproteins:
Two high molecular weight glycoproteins are widely distributed in the matrix of DCT. Fibronectin promotes cell adhesion of different soft tissue cells to each other as well as to collagen and other matrix substrates. It is composed of two disulfide-bonded subunits. Laminin is a major component of basal lamina. The basal lamina provides scaffolding along which regenerating cells can migrate following injury to epithelial, muscle, and nervous tissues.
Two high molecular weight glycoproteins are widely distributed in the matrix of DCT. Fibronectin promotes cell adhesion of different soft tissue cells to each other as well as to collagen and other matrix substrates. It is composed of two disulfide-bonded subunits. Laminin is a major component of basal lamina. The basal lamina provides scaffolding along which regenerating cells can migrate following injury to epithelial, muscle, and nervous tissues.
Other glycoproteins include fibromodulin, link protein,osteopontin, tenascin, and thrombospondin. Examples of their varied functions include modulating cell attachments (fibronectin, tenascin, thrombospondin), controlling collagen fibril formation (fibromodulin), stabilizing PG aggregates in cartilage (link protein), and promoting tissue calcification (osteopontin).
Cells:
Cells of DCT fall into two general categories: those that are produced and remain locally (adipose cells, fibroblasts), and those cells that are produced elsewhere and are transient (leukocytes, macrophages, mast cells, plasma cells). Of the local cells, adipose cells store neutral fats for energy and heat production. Fibroblasts, and specialized osteoblasts in bone and chondroblasts in cartilage, are widely distributed in DCT. They are responsible for the production of protein fibers (collagen, elastin, reticulin) and the ECM (GAGs, PGs, glycoproteins) in the maintenance and repair of DCT.
Cells:
Cells of DCT fall into two general categories: those that are produced and remain locally (adipose cells, fibroblasts), and those cells that are produced elsewhere and are transient (leukocytes, macrophages, mast cells, plasma cells). Of the local cells, adipose cells store neutral fats for energy and heat production. Fibroblasts, and specialized osteoblasts in bone and chondroblasts in cartilage, are widely distributed in DCT. They are responsible for the production of protein fibers (collagen, elastin, reticulin) and the ECM (GAGs, PGs, glycoproteins) in the maintenance and repair of DCT.
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Phagocytosis of foreign antigens is an important function of certain transient cells. Tissue macrophages are the first line of phagocytic defense during infection and inflammation. The next line of phagocytic activity comes from neutrophilic leukocytes, also known as polymorphonuclear leukocytes (PMNLs) or “polys” for short. These leukocytes migrate across the blood vessel wall to reach the bacteria. Monocytes are white blood cell macrophages that play a delayed role in phagocytosis, often following the tissue macrophages and PMNLs. Phagocytes will multiply in great numbers during the early stages of inflammation in an effort to control the spread of antigens and clean up the foreign debris. Eosinophilic leukocytes release enzymes that destroy largeparasites and help modulate allergic inflammatory reactions.
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Basophilic leukocytes are responsible for releasing histamine, a vasodilator, into the bloodstream in certain immune reactions. Mast cells, similar to basophils, release pharmacologically active substances, such as histamine, to produce an immediate hypersensitivity response to allergic reactions. Plasma cells, derived from activated B lymphocytes, produce antibodies and provide humoral immunity. T lymphocytes are responsible for cell-mediated immunity and integrity of dens-connective tissue.
