Chapter 7: Cartilage PDF

# Chapter 7: Cartilage ## Hyaline Cartilage - Matrix - Cartilage Cells - Perichondrium ## Elastic Cartilage ## Fibrocartilage ## Cartilage Formation, Growth, & Repair ## Summary of Key Points ## Assess Your Knowledge Cartilage, a tough and durable form of supporting connective tissue, characteris...

# Chapter 7: Cartilage ## Hyaline Cartilage - Matrix - Cartilage Cells - Perichondrium ## Elastic Cartilage ## Fibrocartilage ## Cartilage Formation, Growth, & Repair ## Summary of Key Points ## Assess Your Knowledge Cartilage, a tough and durable form of supporting connective tissue, characteristically displays an extracellular matrix (ECM) with very high concentrations of GAGs and proteoglycans, all interacting with collagen and elastic fibers. Structural features of its matrix make cartilage ideal for a variety of mechanical and protective roles within the adult skeleton and elsewhere. **Figure 7-1: Distribution of cartilage in adults** - Cartilages are made up of chondrocytes **Locations for Different Types of Cartilage** | Location | Type of Cartilage | |---|---| | Cartilage in external ear | Elastic Cartilage | | Cartilages in nose | Elastic Cartilage | | Epiglottis | Elastic Cartilage | | Larynx | Elastic Cartilage | | Trachea | Hyaline Cartilage | | Lung | Hyaline Cartilage | | Respiratory tract cartilages in the lungs, trachea, and larynx | Hyaline Cartilage | | Articular cartilage of a joint | Hyaline Cartilage | | Costal cartilage | Hyaline Cartilage | | Cartilage of intervertebral disc | Fibrocartilage | | Pubic symphysis | Fibrocartilage | | Meniscus (padlike fibrocartilage in knee joint) | Fibrocartilage | | Articular cartilage of a joint | Hyaline Cartilage | **Explanation:** - **(a)** There are three types of adult cartilage associated with areas of the skeleton, particularly in joints and where pliable support is useful, as in the ribs, ears and nose. Cartilage support of other tissues throughout the respiratory tract is also prominent. - **(b) Hyaline cartilage:** The photomicrographs show the key features of hyaline cartilage. - **(c) Elastic cartilage:** The photomicrographs show the key features of elastic cartilage. - **(d) Fibrocartilage:** The photomicrographs show the key features of fibrocartilage. Dense connective tissue of perichondrium appears here with hyaline and elastic cartilage. **Cartilage ECM:** - Cartilage ECM has a firm yet flexible consistency that allows the tissue to bear mechanical stresses without permanent distortion. - In the respiratory tract, ears and nose, cartilage forms the framework supporting softer tissues. - Because of its resiliency and smooth, lubricated surface, cartilage provides cushioning and sliding regions within skeletal joints and facilitates bone movements. - As described in Chapter 8, cartilage also guides development and growth of long bones, both before and after birth. **Cartilage Cells and ECM:** - Cartilage consists of cells called chondrocytes (Gr. chondros, cartilage + kytos, cell) and chondroblasts embedded in the ECM which, unlike connective tissue proper, contains no other cell types. - Chondroblasts undergo mitosis and secrete ECM components, maturing as nondividing chondrocytes which also produce the ECM and maintain it longterm. - As cartilage develops the cells occupy matrix cavities called lacunae. - **Type II collagen:** The physical properties of cartilage depend on electrostatic bonds between type II collagen fibrils, hyaluronan, and the sulfated GAGs on densely packed proteoglycans. - **Semirigid consistency:** Its semirigid consistency relates to the water binding the negatively charged hyaluronan and GAG chains that extend from proteoglycan core proteins, all components enclosed within a complex meshwork of thin type II collagen fibrils. - **Shock absorber:** The high content of bound water allows cartilage to serve as a shock absorber, an important functional role. - **Avascular:** All types of cartilage lack vascular supplies with chondrocytes receiving nutrients and oxygen by diffusion from capillaries in surrounding connective tissue (the perichondrium). - In some skeletal elements, large blood vessels do traverse cartilage to supply other tissues, but these vessels release few nutrients to he chondrocytes. - **Low metabolic activity:** As expected of cells in an avascular tissue, chondrocytes exhibit low metabolic activity. Cartilage also lacks nerves. - **Perichondrium:** The perichondrium, a sheath of dense connective tissue surrounding most cartilaginous structures forms an interface between the cartilage and tissues supported by the cartilage. The perichondrium harbors the blood supply serving the cartilage and a small neural component. - **Articular cartilage:** Articular cartilage, which covers the ends of bones in movable joints and erodes during arthritic degeneration, lacks perichondrium but its chondrocytes receive sufficient oxygen and nutrients from the synovial fluid. **Figure 7-2: The structure of cartilage matrix and cells:** **Diagram (a): Molecular Interactions:** - **Type II collagen:** A schematic representation of the most abundant molecules in cartilage matrix shows the interaction between Type II collagen fibrils and proteoglycans linked hylauronan. - **Link protein:** Link proteins noncovalently bind the protein core of proteoglycans to the linear hyaluronan molecules. - **Chondroitin sulfate:** The chondroitin sulfate side chains of the proteoglycans electrostatically bind to the collagen fibrils, forming a cross-linked matrix. - **Hydrated and pliable:** Physical properties of these matrix components produce a highly hydrated, pliable material with great strength. Water represents approximately 75% of the wet weight of hyaline cartilage. **Diagram (b): Transitional area between the perichondrium and the cartilage matrix:** - **Fibroblast-like progenitor cells:** A diagram of the transitional area between the perichondrium and the cartilage matrix. Fibroblast-like progenitor cells in the perichondrium give rise to larger chondroblasts, which divide and differentiate as chondrocytes. - **Matrix components:** These functional cells produce matrix components and exist in lacunae surrounded by the matrix. - **Territorial matrix:** The ECM immediately around each lacuna, called the territorial matrix, contains mostly proteoglycans and sparse collagen; that more distant from lacunae, the interterritorial matrix, contains more collagen and may be less basophilic. **Three Main Types of Cartilage** As shown in Figure 7-1, variations in the composition of the matrix characterize three main types of cartilage: hyaline cartilage, elastic cartilage, and fibrocartilage. **Table 7-1: Important Features of the Major Cartilage Types:** | Type of Cartilage | Main Features of Extracellular Matrix | Major Cells | Typical arrangement of chondrocytes | Presence of perichondrium | Main locations | Main functions | |---|---|---|---|---|---|---| | Hyaline Cartilage | Homogeneous, with Type II collagen and aggrecan | Chondrocytes, chondroblasts | Isolated or in small isogenous groups | Yes (except at epiphyses and articular cartilage) | Many components of upper respiratory tract; articular ends and epiphyseal plates of long bones; fetal skeleton. | Provides smooth, low-friction surfaces in joints; structural support for respiratory tract | | Elastic Cartilage | Type II collagen, aggrecan, and darker elastic fibers | Chondrocytes, chondroblasts | Usually in small isogenous groups | Yes | External ear, external acoustic meatus, auditory tube; epiglottis and certain other laryngeal cartilages | Provides flexible shape and support of soft tissues | | Fibrocartilage | Type II collagen and large areas of dense connective tissue with Type I collagen | Chondrocytes, fibroblasts | Isolated or in isogenous groups arranged axially | No | Intervertebral discs, pubic symphysis, meniscus, and certain other joints; insertions of tendons | Provides cushioning, tensile strength, and resistance to tearing and compression | **Hyaline Cartilage**: - *Hyaline (Gr. hyalos, glass) cartilage,* the most common of the three types, appears homogeneous and semitransparent in the fresh state. - In adults hyaline cartilage can be found in the articular surfaces of movable joints, in the walls of larger respiratory passages (nose, larynx, trachea, bronchi), in the ventral ends of ribs, where they articulate with the sternum, and in the epiphyseal plates of long bones, where it makes possible longitudinal bone growth (Figure 7-1). - In the embryo, hyaline cartilage forms the temporary skeleton later gradually replaced by bone. **Medical Application**: - Many genetic conditions in humans or mice that cause defective cartilage, joint deformities, or short limbs are due to recessive mutations in genes for collagen type II, the aggrecan core protein, the sulfate transporter, and other proteins required for normal chondrocyte function. **Osteoarthritis:** - 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. **Matrix Components of Hyaline Cartilage:** - **Collagen:** Collagen makes up 40% of hyaline cartilage's dry weight, with all of it embedded in the firm, hydrated gel of proteoglycans and structural glycoproteins. - **Type II collagen:** In routine histology preparations, the proteoglycans confer variable basophilia on this matrix, making the thin collagen fibrils barely discernible. Type II collagen predominates in hyaline cartilage, with lesser amounts of minor collagens also present. - **Aggrecan:** Aggrecan (core protein 250 kDa), with approximately 150 GAG side chains of chondroitin sulfate and keratan sulfate, makes up the most abundant proteoglycan of hyaline cartilage. - **Hyaluronan:** Hundreds of these proteoglycans bind noncovalently by link proteins to long polymers of hyaluronan, as shown schematically in Figure 7–2a and discussed in Chapter 5. - **Water:** These proteoglycan complexes adhere further to the surface of type II collagen fibrils (Figure 7–2a). Water bound to GAGs in the proteoglycans constitutes up to 60%-80% of the weight of fresh hyaline cartilage. - **Chondronectin:** The structural multiadhesive glycoprotein chondronectin represents another key component of cartilage matrix. Like fibronectin in other connective tissues, chondronectin binds specifically to GAGs, collagen and integrins, mediating transient adherence of chondrocytes to the ECM. - **Territorial matrix:** Staining variations within the matrix reflect local differences in its molecular composition. Immediately surrounding each chondrocyte, the ECM is richer in GAGs than collagen, often causing these areas of territorial matrix to stain more darkly than the intervening areas of interterritorial matrix (Figures 7-2b and 7–3). **Cartilage Cells:** - **Chondrocytes:** Chondrocytes can survive w/o oxygen Survive using synovial fluid. Cells occupy only a small volume of hyaline cartilage. - **Chondroblasts:** At the periphery of the cartilage, young chondrocytes and chondroblasts have an elliptic shape, with the long axes parallel the surface (Figure 7–3). Deeper in the cartilage they become rounded and often appear in small groups of cells called isogenous aggregates, originating from a single chondroblast by mitotic divisions. - **ECM components:** As these chondrocytes become more active in secreting collagens and other ECM components, the new matrix separates the cells which then occupy separate lacunae. **Figure 7-3: Hyaline Cartilage** **Diagram (a)** - The upper part of the photo shows the perichondrium (P), an example of dense connective tissue consisting of type I collagen primarily. Among the fibroblastic cells of the perichondrium are indistinguishable mesenchymal stem cells. There is a gradual transition and differentiation of cells from the perichondrium to the cartilage, with elongated fibroblast-like cells becoming larger and more rounded as chondroblasts and chondrocytes (C). These become localized within lacunae surrounded by the matrix (M) which these cells secreted. (×200; H&E) **Diagram (b)** - The thin region of hyaline cartilage shown here has perichondrium (P) on both sides and shows larger lacunae containing isogenous groups of chondrocytes (C) within the matrix (M). Such groups of two, four or more cells arise by mitosis of chondroblasts; the cells will separate into individual lacunae as they begin to secrete matrix. Territorial matrix immediately around the chondrocytes displays more intense basophilia than interterritorial matrix farther from the cells, indicating its greater density of sulfated GAGs. (×160; H&E). **Cartilage cell behavior:** - Cartilage cells and matrix may shrink slightly during routine histologic preparation, resulting in both the irregular shape of the chondrocytes and their retraction from the matrix. - In living tissue, chondrocytes fill their lacunae completely. **Metabolic Processes in Hyaline Cartilage:** - **Avascular:** Because of the cartilage matrix avascularity, chondrocytes respire under low-oxygen tension. - **Glycolysis:** Hyaline cartilage cells metabolize glucose by anaerobic glycolysis primarily. - **Nutrient Diffusion:** Nutrients from the blood diffuse to all the chondrocytes from the cartilage surface, with movement of water and solutes in the cartilage matrix promoted by intermittent tissue compression and decompression during body movements. - **Limiting diffusion:** The limits of such diffusion define the maximum thickness of hyaline cartilage, which usually exists as small, thin plates. **Medical Application** - In contrast to other forms of cartilage and most other tissues, hyaline cartilage is susceptible to partial or isolated regions of calcification during aging, especially in the costal cartilage adjacent to the ribs. - **Calcification:** Calcification of the hyaline matrix, accompanied by degenerative changes in the chondrocytes, is a common part of the aging process and in many respects resembles endochondral ossification by which bone is formed. - **Growth hormones and growth factors:** Several hormones and growth factors accelerate blast synthesis of sulfated GAGs and secretion of proteoglycans, with the pituitary-derived protein called growth hormone or somatotropin serving as a major regulator of hyaline cartilage growth. - **Insulin-like growth factors:** This hormone acts indirectly, promoting the endocrine release from the liver of insulin-like growth factors, or somatomedins, which directly stimulate the cells of hyaline cartilage. - **Medical Application:** 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. **Perichondrium:** - Except in the articular cartilage of joints, all hyaline cartilage has a covering layer of dense connective tissue, the perichondrium, essential for the growth and maintenance of the cartilage (Figures 7-2b and 7-3). - **Outer Region:** The outer region of the perichondrium consists primarily of collagen type I fibers and fibroblasts; but an inner layer adjoining the cartilage matrix also contains mesenchymal stem cells that provide a source for new chondroblasts that divide and differentiate into chondrocytes. **Elastic Cartilage:** - Elastic cartilage has features essentially like those of hyaline cartilage except that in addition to the meshwork of collagen type II fibrils it contains an abundant network of elastic fibers (Figures 7–4 and 7–1c), which give fresh elastic cartilage a yellowish color. - **Elastic fibers:** With appropriate staining the elastic fibers usually appear as dark bundles distributed unevenly through the matrix. **Figure 7-4: Elastic Cartilage** - **Diagram (a):** The chondrocytes (C) and overall organization of elastic cartilage resemble those of hyaline cartilage, but the matrix (M) also contains elastic fibers that can be seen as darker components with proper staining. The abundant elastic fibers provide greater flexibility to this type of cartilage. The section in part b includes perichondrium (P) that is also like that of hyaline cartilage. (a) ×160; Hematoxylin and orcein. - **Diagram (b):** (b) ×180; Weigert resorcin and van Gieson. **Locations and characteristics of Elastic Cartilage** - More flexible than hyaline cartilage, elastic cartilage occurs in the external ear, the walls of the external auditory canals, the auditory (Eustachian) tubes, the epiglottis, and the upper respiratory tract. - Elastic cartilage in these locations includes a perichondrium like that of most hyaline cartilage. - Throughout elastic cartilage the cells resemble those of hyaline cartilage both physiologically and structurally. **Fibrocartilage:** - Fibrocartilage takes various forms in different structures but appears as a mixture of hyaline cartilage and dense connective tissue (Figures 7-5 and 7- 1d). - **Locations:** It develops in intervertebral discs, in attachments of certain ligaments, and in the pubic symphysis—all places where it serves as very tough, yet cushioning support tissue for bone. **Figure 7-5: Fibrocartilage:** - Fibrocartilage varies histologically in different structures but is always essentially a mixture of hyaline cartilage and dense connective tissue. - In a small region of intervertebral disc, the axially arranged aggregates of chondrocytes (C) are seen to be surrounded by small amounts of matrix and separated by larger regions with dense collagen and scattered fibroblasts with elongated nuclei (arrows). (×250; Picrosirius-hematoxylin) **Fibrocartilage cell arrangement:** - Cells of fibrocartilage occur singly and often in aligned isogenous aggregates, producing a sparse ECM of type II collagen and other matrix components. - **Type I collagen:** Areas with chondrocytes and hyaline matrix become separated by other regions with fibroblasts and dense bundles of type I collagen, which confer extra tensile strength to this tissue (Figure 7-5). - **Acidophilic:** The relative scarcity of proteoglycans overall makes fibrocartilage matrix more acidophilic than that of hyaline or elastic cartilage. Fibrocartilage lacks a distinct surrounding perichondrium. **Intervertebral Discs:** - Intervertebral discs of the spinal column consist primarily of fibrocartilage and act as lubricated cushions and shock absorbers, held in place by ligaments and preventing damage to adjacent vertebrae from abrasive forces or impacts. - **Chapter 8:** Intervertebral discs are discussed further with joints in Chapter 8. **Table 7-1 (Summary of Cartilage Types):** - Again, Table 7–1 summarizes the important features of the three major types of cartilage. **Cartilage Formation, Growth, & Repair:** - **Low metabolic rate:** All cartilage develops from embryonic mesenchyme in the process of chondrogenesis (Figure 7-6). - **Chondrogenesis:** The first indications of cell differentiation appear as the rounding of mesenchymal cells, which retract their extensions, multiply rapidly and become more densely packed together. - **Chondroblasts and chondrocytes:** As mentioned, the terms “chondroblasts” and “chondrocytes,” respectively, generally refer to the cartilage cells during and after the period of rapid proliferation. - **Basophilic cytoplasm:** At both stages, the cells have basophilic cytoplasm rich in RER for collagen synthesis (Figure 7-7). **Figure 7-6: Chondrogenesis** - **Diagram (a): Mesenchyme** Diagrams here depict the major stages of embryonic cartilage formation, or chondrogenesis. Mesenchyme represents the precursor for all types of cartilage - **Diagram (b): Mitosis** Mitosis and initial cell differentiation produce a tissue with condensations of rounded cells called chondroblasts. - **Diagram (c): Chondroblasts** Chondroblasts then separate from one another by their production of the various matrix components, which collectively swell with water and form the very extensive ECM. - **Diagram (d): Multiplication** Multiplication of chondroblasts within the matrix gives rise to isogenous cell aggregates surrounded by a condensation of territorial matrix. In mature cartilage, this interstitial mitotic activity ceases and all chondrocytes typically become more widely separated by their production of matrix. **Figure 7-7: Chondrocytes in growing cartilage** - This TEM of fibrocartilage shows chondrocytes with abundant RER actively secreting the collagen-rich matrix. Bundles of collagen fibrils, sectioned in various orientations, predominate around the chondrocytes of this fibrocartilage, with collagen types I and II both present. Chondrocytes in growing hyaline and elastic cartilage have more prominent Golgi complexes and synthesize abundant proteoglycans in addition to collagen. (×3750) **Cartilage Growth:** - Once formed cartilage tissue enlarges both by **interstitial growth**, involving mitotic division of preexisting chondroblocks, and by **appositional growth**, which involves chondroblast differentiation from progenitor cells in the perichondrium (Figure 7-2b). - In both cases matrix synthesis contributes most volumetric growth of the cartilage. - **Appositional growth:** Appositional growth of cartilage becomes more important during postnatal development, although as described in Chapter 8 interstitial growth in cartilaginous regions within long bones allows increasing length of these structures. - **Articular joints:** Cartilage at the surfaces of articular joints often becomes eroded, with cell and matrix replacement reliant on the remaining cells since such joints lack perichondrium to add cells by appositional growth. **Cartilage Repair:** - Except in young children, damaged cartilage undergoes slow and often incomplete **repair**, primarily dependent on cells from the perichondrium, which invade the injured area and produce new connective tissue instead of forming new cartilage. - As mentioned earlier the poor capacity of cartilage for repair or regeneration is due in part to its avascularity and low metabolic rate. **Cartilage Summary of Key Points** - **Resilient connective tissue** - **ECM:** Cells of cartilage, chondrocytes, make up a small percentage of the tissue's mass, which is mainly a flexible mass of extracellular matrix (ECM). - **Collagen:** Chondrocytes lie embedded within lacunae surrounded by the ECM. Cartilage ECM typically includes collagen as well as abundant proteoglycans, notably aggrecan, which bind a large amount of water. - **Avascular:** Cartilage always lacks blood vessels, lymphatics and nerves, but usually has a surrounding dense connective tissue perichondrium that is vascularized. - **Three main types:** There are three major forms of cartilage: (1) hyaline cartilage, (2) elastic cartilage, and (3) fibrocartilage. **Hyaline Cartilage** - **Homogeneous:** The ECM of hyaline cartilage appears homogenous and glassy, rich in fibrils of type II collagen and aggrecan complexes with bound water. - **Territorial matrix:** The ECM has less collagen and more proteoglycan immediately around the lacunae, producing slight staining differences in this territorial matrix. - **Isogenous groups:** Chondrocytes occur singly or in small, mitotically derived isogenous groups. - **Perichondrium:** Perichondrium is usually present, but not with hyaline cartilage of articular surfaces or the epiphyses of growing long bones. **Elastic Cartilage** - **Abundant elastic fibers:** Elastic cartilage resembles hyaline cartilage in its chondrocytes and major ECM components, but its matrix includes abundant elastic fibers, visible with special stains, which increase the tissue's flexibility. - **Locations:** Elastic cartilage provides flexible support for the external ear as well as certain structures of the middle ear and larynx; it always includes surrounding perichondrium. **Fibrocartilage:** - **Combination of hyaline cartilage and connective tissue:** Fibrocartilage contains varying combinations of hyaline cartilage in variable amounts of dense connective tissue. - **Histological layering:** Histologically it consists of small chondrocytes in a hyaline matrix, usually layered with larger areas of bundled type I collagen with scattered fibroblasts. - **Locations:** Fibrocartilage provides very tough, strong support at tendon insertions and in intervertebral discs and certain other joints. **Cartilage Formation, Growth, & Repair** - **Mesenchyme:** All forms of cartilage develop from embryonic mesenchyme. - **Interstitial and appositional growth:** Cartilaginous structures grow by mitosis of existing chondroblasts in lacunae (interstitial growth) or formation of new chondroblasts peripherally from progenitor cells in the perichondrium (appositional growth). - **Repair:** Repair or replacement of injured cartilage occurs very slowly and ineffectively, due in part to the tissue's avascularity and low metabolic rate. **Cartilage: ** **Assess Your Knowledge** 1. **Shock absorbing:** The molecular basis for the shock absorbing properties of cartilage involves which of the following? - a. Electrostatic interaction of proteoglycans with type IV collagen - b. Ability of glycosaminoglycans to bind anions - c. Noncovalent binding of glycosaminoglycans to protein cores - d. Sialic acid residues in the glycoproteins - e. Hydration of glycosaminoglycans 2. **Distinguishing feature of cartilage:** What distinguishes cartilage from most other connective tissues? - a. Its extracellular matrix is rich in collagen. - b. Its predominant cell type is a mesenchymal derivative. - c. Its predominant cell type secretes both fibers and proteoglycans. - d. It lacks blood vessels. - e. It functions in mechanical support. 3. **Typical feature of elastic cartilage:** Which feature is typical of elastic cartilage? - a. Primary skeletal tissue in the fetus - b. No identifiable perichondrium - c. Found in intervertebral discs - d. Most widely distributed cartilage type in the body - e. Collagen is mainly type II 4. **Collagen-poor and proteoglycan-rich:** Which area in cartilage is relatively collagen-poor and proteoglycan-rich?