CARTILAGE. Dr. Emad I Shaqoura M.D, M.Sc. Anatomy Faculty of Medicine, Islamic University-Gaza October, 2015

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1 CARTILAGE Dr. Emad I Shaqoura M.D, M.Sc. Anatomy Faculty of Medicine, Islamic University-Gaza October, 2015

2 Introduction Hyaline Cartilage Elastic Cartilage Fibrocartilage Cartilage Formation, Growth, & Repair

3

4 Cartilage is a tough, flexible form of connective tissue. It is composed of: 1. Chondrocytes: that synthesize and maintain ECM components and are located in matrix cavities called lacunae. 2. An extracellular matrix (ECM) rich in GAGs and proteoglycans, which interact with collagen and elastic fibers.

5 The physical properties of cartilage depend on electrostatic bonds between the collagen and elastin fibers and the GAGs. Its semi-rigid consistency is attributable to water bound to the negatively charged sulfated GAGs. Cartilage is avascular and receives nutrients by diffusion from capillaries in adjacent connective tissue (perichondrium), so, chondrocytes exhibit low metabolic activity. Cartilage also lacks lymphatic vessels and nerves.

6 FIGURE 7-1 Copyright McGraw-Hill Companies

7 Support of soft tissue e.g., respiratory tract, ear & nose. Cartilage provides shock absorbing and sliding regions within joints and facilitates bone movements. Cartilage also guides development and growth of long bones, both before and after birth.

8 Hyaline Cartilage Elastic Cartilage Fibrocartilage

9

10 Hyaline (Gr. hyalos, glassy) cartilage, is the most common of the three forms. It is homogeneous and semitransparent in the fresh state.

11 Sites 1. Articular surfaces of movable joints. 2. Walls of larger respiratory passages (nose, larynx, trachea, bronchi). 3. Costal cartilages. 4. Epiphyseal plates of long bones. 4. Temporary skeleton of the embryo.

12 Osteoarthritis, a chronic condition that commonly occurs during aging, involves the gradual loss or changed physical properties of the hyaline cartilage that lines the articular ends of bones in joints. Joints that are weight bearing (knees, hips) or heavily used (wrist, fingers) are most prone to cartilage degeneration. Fragments released by wear-and-tear to the articular cartilage trigger secretion of matrix metalloproteinases and other factors from macrophages in adjacent tissues, which exacerbate damage and cause pain and inflammation within the joint.

13 The dry weight of hyaline cartilage is 40% collagen (mainly type II) embedded in a firm, hydrated gel of proteoglycans and structural glycoproteins. In routine histology preparations, the proteoglycans cause the matrix to be generally basophilic and the thin collagen fibrils are barely discernible. Aggrecan (250 kd), with approximately 150 GAG side chains of chondroitin sulfate and keratan sulfate, is the most abundant proteoglycan of hyaline cartilage.

14 Hundreds of aggrecan proteoglycans are bound noncovalently by link proteins to long polymers of hyaluronic acid. These proteoglycan complexes bind further to the surface of type II collagen fibrils. Water bound to GAGs in the proteoglycans constitutes up 60%-80% of the weight of fresh hyaline cartilage.

15 FIGURE 7-2 Copyright McGraw-Hill Companies

16 Chondronectin is the main glycoprotein of cartilage that binds specifically to GAGs, collagen type II, and integrins, mediating the adherence of chondrocytes to the ECM. Staining variations within the matrix reflect local differences in its molecular composition. Immediately surrounding each chondrocyte, the territorial matrix (richer in GAGs) stains differently from the intervening areas of interterritorial matrix (more collagen).

17 FIGURE 7-2 Copyright McGraw-Hill Companies

18 Cells occupy relatively little of the hyaline cartilage mass. Two cell types are present: 1. Young chondrocytes (chondroblasts): Present at the periphery of the cartilage. Have an elliptic shape, with the long axis parallel to the surface. 2. Mature Chondrocytes: Deeper in the cartilage. They are round. They may appear in groups of up to eight cells that originate from mitotic divisions of a single chondrocyte and are called isogenous aggregates.

19 FIGURE 7-2 Copyright McGraw-Hill Companies

20 FIGURE 7-3 Copyright McGraw-Hill Companies

21 As the chondrocytes become more active in secreting collagens and other ECM components, the aggregated cells are pushed apart and occupy separate lacunae. Cartilage cells and the matrix often shrink during routine histologic preparation, resulting in both the irregular shape of the chondrocytes and their retraction from the matrix. In living tissue, and in properly prepared sections, the chondrocytes fill the lacunae completely.

22 Because cartilage is devoid of blood capillaries, chondrocytes respire under low-oxygen tension. Hyaline cartilage cells metabolize glucose mainly by anaerobic glycolysis to produce lactic acid as the end product. Chondrocyte synthesis of sulfated GAGs and secretion of proteoglycans are accelerated by many hormones and growth factors e.g., GH.

23 Cells of cartilage can give rise to either benign (chondroma) or slow-growing, malignant (chondrosarcoma) tumors in which cells produce normal matrix components. Chondrosarcomas seldom metastasize and are generally removed surgically.

24 Except in the articular cartilage of joints, all hyaline cartilage is covered by a layer of dense connective tissue, the perichondrium, which is essential for the growth and maintenance of cartilage. The perichondrium consists largely of collagen type I fibers and fibroblasts. Among these fibroblasts in the inner layer of the perichondrium are progenitor cells for chondroblasts that divide and differentiate into chondrocytes.

25 FIGURE 7-2 Copyright McGraw-Hill Companies

26 FIGURE 7-3 Copyright McGraw-Hill Companies

27 Nutrients from the blood diffuse from the perichondrium to reach the deeper chondrocytes. Transport of water and solutes in the matrix is promoted by the pumping action of intermittent cartilage compression and decompression. Because of the limits of diffusion, the maximum thickness of the hyaline cartilage is limited and it usually exists as small, thin plates.

28 The inability of cartilage to regenerate or to be repaired fully may be attributed to the chondrocytes immobility, low metabolic and mitotic rates, and avascularity. If a cartilage injury involves the perichondrium, new chondroblasts and fibroblasts may be mobilized and limited repair can occur, but most of the new tissue produced is dense connective tissue and normal function of the cartilage is often impaired.

29

30 Elastic cartilage is similar to hyaline cartilage except that it contains an abundant network of elastic fibers in addition to collagen type II, which give fresh elastic cartilage a yellowish color. Demonstration of the elastic fibers usually requires stains such as orcein or resorcin fuchsin.

31 FIGURE 7-4 Copyright McGraw-Hill Companies

32 Elastic cartilage is found in: 1. The auricle of the ear. 2. The walls of the external auditory canals. 3. The auditory (eustachian) tubes. 4. The epiglottis, and the cuneiform cartilage in the larynx. Elastic cartilage in these locations includes a perichondrium similar to that of most hyaline cartilage.

33

34 Fibrocartilage is essentially a combination of hyaline cartilage and dense connective tissue with gradual transitions between these tissues. It is found in intervertebral discs, in attachments of certain ligaments, and in the pubic symphysis. Chondrocytes of fibrocartilage occur singly and in aligned isogenous aggregates and produce matrix containing type II collagen.

35 FIGURE 7-5 Copyright McGraw-Hill Companies

36 Regions with chondrocytes and hyaline matrix are separated by other regions containing bundles of type I collagen and scattered fibroblasts. The relative scarcity of proteoglycans makes the matrix of fibrocartilage more acidophilic than that of hyaline or elastic cartilage. There is no distinct surrounding perichondrium in fibrocartilage.

37

38 All cartilage forms from embryonic mesenchyme in the process of chondrogenesis. The first indication of cell differentiation is the rounding up of the mesenchymal cells, which retract their extensions, multiply rapidly, and become more densely packed together. The dividing cells are typically called chondroblasts and chondrocytes when proliferation has ceased; both have basophilic cytoplasm rich in RER for collagen synthesis.

39 FIGURE 7-6 Copyright McGraw-Hill Companies

40 FIGURE 7-7 Copyright McGraw-Hill Companies

41 Production of the ECM encloses the cells in their lacunae and then gradually separates chondroblasts from one another. During embryonic development, the differentiation of cartilage takes place primarily from the center outward; therefore the more central cells have the characteristics of chondrocytes, whereas the peripheral cells are typical chondroblasts. The superficial mesenchyme forms the perichondrium.

42 The cartilage tissue enlarges by: 1. Interstitial growth, resulting from the mitotic division of preexisting chondroblasts. 2. Appositional growth, which involves differentiation of new chondroblasts from the perichondrium. In both cases, the synthesis of matrix contributes greatly to the growth of the cartilage.

43 Appositional growth of cartilage is more important during postnatal development, although interstitial growth in the articular cartilage and epiphyseal plates of long bones is important in increasing the length of long bones. In articular cartilage, cells and matrix near the articulating surface are gradually worn away and must be replaced from within, because there is no perichondrium to add cells by appositional growth.

44 Damaged cartilage undergoes slow and often incomplete repair, except in young children. It occurs primarily by activity of cells in the perichondrium, which invade the injured area and produce new cartilage. In extensively damaged areas the perichondrium produces a scar of dense connective tissue instead of forming new cartilage. The poor capacity of cartilage for repair or regeneration is due in part to the avascularity of this tissue.

45 In contrast to other forms of cartilage and other tissues, hyaline cartilage is susceptible to calcification during aging. Calcification of the hyaline matrix, accompanied by degenerative changes in the chondrocytes, is a common part of the aging process. It resembles endochondral ossification by which bone is formed in many respects.

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