Junqueira_s Basic Histology, Text and Atlas, 14th Edition 4.pdf

C H A P T E R BONE CELLS 8 Bone 138 OSTEOGENESIS 148 Osteoblasts 138 Intramembranou...

C H A P T E R BONE CELLS 8 Bone 138 OSTEOGENESIS 148 Osteoblasts 138 Intramembranous Ossification 149 Osteocytes 142 Endochondral Ossification 149 Osteoclasts 143 BONE REMODELING & REPAIR 152 BONE MATRIX 143 METABOLIC ROLE OF BONE 153 PERIOSTEUM & ENDOSTEUM 143 JOINTS 155 TYPES OF BONE 143 SUMMARY OF KEY POINTS 158 Lamellar Bone 145 ASSESS YOUR KNOWLEDGE 159 Woven Bone 148 A s the main constituent of the adult skeleton, bone tis- All bones are lined on their internal and external surfaces sue (Figure 8–1) provides solid support for the body, by layers of connective tissue containing osteogenic cells— protects vital organs such as those in the cranial and endosteum on the internal surface surrounding the marrow thoracic cavities, and encloses internal (medullary) cavities cavity and periosteum on the external surface. containing bone marrow where blood cells are formed. Bone Because of its hardness, bone cannot be sectioned rou- (or osseous) tissue also serves as a reservoir of calcium, phos- tinely. Bone matrix is usually softened by immersion in a phate, and other ions that can be released or stored in a con- decalcifying solution before paraffin embedding, or embed- trolled fashion to maintain constant concentrations in body ded in plastic after fixation and sectioned with a specialized fluids. microtome. In addition, bones form a system of levers that multiply › BONE CELLS the forces generated during skeletal muscle contraction and transform them into bodily movements. This mineralized tis- sue therefore confers mechanical and metabolic functions to the skeleton. Osteoblasts Bone is a specialized connective tissue composed of cal- Originating from mesenchymal stem cells, osteoblasts pro- cified extracellular material, the bone matrix, and following duce the organic components of bone matrix, including type three major cell types (Figure 8–2): I collagen fibers, proteoglycans, and matricellular glycopro- teins such as osteonectin. Deposition of the inorganic com- Osteocytes (Gr. osteon, bone + kytos, cell), which are ponents of bone also depends on osteoblast activity. Active found in cavities (lacunae) between bone matrix layers osteoblasts are located exclusively at the surfaces of bone (lamellae), with cytoplasmic processes in small canaliculi matrix, to which they are bound by integrins, typically form- (L. canalis, canal) that extend into the matrix (Figure 8–1b) ing a single layer of cuboidal cells joined by adherent and gap Osteoblasts (osteon + Gr. blastos, germ), growing cells junctions (Figure 8–3). When their synthetic activity is com- which synthesize and secrete the organic components of pleted, some osteoblasts di%erentiate as osteocytes entrapped the matrix in matrix-bound lacunae, some flatten and cover the matrix Osteoclasts (osteon + Gr. klastos, broken), which are surface as bone lining cells, and the majority undergo giant, multinucleated cells involved in removing calcified apoptosis. bone matrix and remodeling bone tissue During the processes of matrix synthesis and calcifica- Because metabolites are unable to di%use through the cal- tion, osteoblasts are polarized cells with ultrastructural features cified matrix of bone, the exchanges between osteocytes and denoting active protein synthesis and secretion. Matrix com- blood capillaries depend on communication through the very ponents are secreted at the cell surface in contact with existing thin, cylindrical spaces of the canaliculi. bone matrix, producing a layer of unique collagen-rich material 138  FIGURE 8–1 Components of bone. C H A P T E R Concentric Nerve lamellae Vein Artery 8 Collagen fiber Canaliculi Bone Bone Cells orientation Diaphysis Central of humerus canal Central canal Osteon External circumferential Osteon lamellae Lacuna Perforating fibers Periosteum Internal Cellular circumferential Osteocyte Fibrous layer lamellae layer Canaliculi Interstitial lamellae (b) Compact bone Inner circumferential lamellae Trabeculae of cancellous bone Perforating Central Endosteum canals canal (a) Section of humerus Osteoclast Space for bone marrow Lamellae Osteocyte Trabeculae in lacuna Canaliculi opening Osteoblasts at surface aligned along trabecula of new bone Canaliculi opening at surface (c) Cancellous bone A schematic overview of the basic features of bone, including the the lacunae. Osteoclasts are monocyte-derived cells in bone three key cell types: osteocytes, osteoblasts, and osteoclasts; required for bone remodeling. their usual locations; and the typical lamellar organization of The periosteum consists of dense connective tissue, with bone. Osteoblasts secrete the matrix that then hardens by calcifica- a primarily fibrous layer covering a more cellular layer. Bone is tion, trapping the differentiating cells now called osteocytes in vascularized by small vessels that penetrate the matrix from the individual lacunae. Osteocytes maintain the calcified matrix and periosteum. Endosteum covers all trabeculae around the marrow receive nutrients from microvasculature in the central canals of the cavities. osteons via very small channels called canaliculi that interconnect 140 CHAPTER 8 Bone FIGURE 8–2 Bone tissue. Newly formed bone tissue decalcified for sec- tioning and stained with trichrome in which the collagen-rich ECM appears bright blue. The tissue is a combination of mesenchymal regions (M) con- taining capillaries, fibroblasts, and osteoprogenitor Oc stem cells and regions of normally calcified matrix Oc with varying amounts of collagen and the three major cell types found in all bone tissue. Bone-forming osteoblasts (Ob) differentiate from osteoprogenitor cells in the periosteum and endosteum, and cover the surfaces of existing bone matrix. Osteoblasts secrete osteoid rich in collagen type I, but also containing proteoglycans and other molecules. As osteoid undergoes calci- Ob Ocl fication and hardens, it entraps some osteoblasts which then differentiate further as osteocytes (Oc) occupying lacunae surrounded by bony matrix. The much less numerous large, multinuclear osteo- M clasts (Ocl), produced by the fusion of blood mono- cytes, reside on bony surfaces and erode the matrix during bone remodeling. (400X; Mallory trichrome) FIGURE 8–3 Osteoblasts, osteocytes, and osteoclasts. Osteoclast Mesenchyme Newly formed Osteoblast Osteocyte Bone matrix matrix (osteoid) Ob Os B Oc M a b (a) Diagram showing the relationship of osteoblasts to the newly cells in the adjacent mesenchyme (M), cover a thin layer of lightly formed matrix called “osteoid,” bone matrix, and osteocytes. Osteo- stained osteoid (Os) on the surface of the more heavily stained blasts and most of the larger osteoclasts are part of the endosteum bony matrix (B). Most osteoblasts that are no longer actively covering the bony trabeculae. secreting osteoid will undergo apoptosis; others differentiate (b) The photomicrograph of developing bone shows the location either as flattened bone lining cells on the trabeculae of bony and morphologic differences between active osteoblasts (Ob) and matrix or as osteocytes located within lacunae surrounded by bony osteocytes (Oc). Rounded osteoblasts, derived from progenitor matrix. (X300; H&E)  Bone Cells 141 called osteoid between the osteoblast layer and the preexisting [Ca10(PO4)6(OH)2] crystals, the first visible step in calcifica- bone surface (Figure 8–3). This process of bone appositional tion. These crystals grow rapidly by accretion of more mineral C H A P T E R growth is completed by subsequent deposition of calcium salts and eventually produce a confluent mass of calcified material into the newly formed matrix. embedding the collagen fibers and proteoglycans (Figure 8–4). The process of matrix mineralization is not completely understood, but basic aspects of the process are shown in › › MEDICAL APPLICATION Figure 8–4. Prominent among the noncollagen proteins Cancer originating directly from bone cells (a primary bone secreted by osteoblasts is the vitamin K–dependent polypep- tumor) is fairly uncommon (0.5% of all cancer deaths), 8 tide osteocalcin, which together with various glycoproteins although a cancer called osteosarcoma can arise in osteo- Bone Bone Cells binds Ca2+ ions and concentrates this mineral locally. Osteo- progenitor cells. The skeleton is often the site of secondary, blasts also release membrane-enclosed matrix vesicles rich metastatic tumors, however, arising when cancer cells move in alkaline phosphatase and other enzymes whose activity into bones via small blood or lymphatic vessels from malig- raises the local concentration of PO43− ions. In the microenvi- nancies in other organs, most commonly the breast, lung, ronment with high concentrations of both these ions, matrix prostate gland, kidney, or thyroid gland. vesicles serve as foci for the formation of hydroxyapatite FIGURE 8–4 Mineralization in bone matrix. Osteoblasts release matrix vesicles Osteoblasts Released matrix vesicles and collagen fibers Osteoid layer Early mineralization around vesicles Matrix becoming confluent between vesicles Mineralized bone From their ends adjacent to the bone matrix, osteoblasts secrete and PO4− ion concentrations cause calcified nanocrystals to form type I collagen, several glycoproteins, and proteoglycans. Some of in and around the matrix vesicles. The crystals grow and mineralize these factors, notably osteocalcin and certain glycoproteins, bind further with formation of small growing masses of calcium hydroxy- Ca2+ with high affinity, raising the local concentration of these ions. apatite [Ca10(PO4)6(OH)2], which surround the collagen fibers and Osteoblasts also release very small membrane-enclosed matrix all other macromolecules. Eventually the masses of hydroxyapatite vesicles containing alkaline phosphatase and other enzymes. These merge as a confluent solid bony matrix as calcification of the matrix enzymes hydrolyze PO4− ions from various matrix macromolecules, is completed. creating a high concentration of these ions locally. The high Ca2+ 142 CHAPTER 8 Bone Osteocytes matrix, and their death is followed by rapid matrix resorption. While sharing most matrix-related activities with osteoblasts, As mentioned some osteoblasts become surrounded by the osteocytes also express many di%erent proteins, including fac- material they secrete and then di%erentiate as osteocytes tors with paracrine and endocrine e%ects that help regulate enclosed singly within the lacunae spaced throughout the min- bone remodeling. The extensive lacunar-canalicular network eralized matrix. During the transition from osteoblasts to osteo- of these cells and their communication with all other bone cytes, the cells extend many long dendritic processes, which also cells allow osteocytes to serve as sensitive detectors of stress- become surrounded by calcifying matrix. The processes thus or fatigue-induced microdamage in bone and to trigger reme- come to occupy the many canaliculi, 250-300 nm in diameter, dial activity in osteoblasts and osteoclasts. radiating from each lacuna (Figures 8–5 and 8–1b). Di%usion of metabolites between osteocytes and blood vessels occurs through the small amount of interstitial fluid › › MEDICAL APPLICATION in the canaliculi between the bone matrix and the osteocytes The network of dendritic processes extending from osteocytes and their processes. Osteocytes also communicate with one has been called a “mechanostat,” monitoring areas within bones another and ultimately with nearby osteoblasts and bone lin- where loading has been increased or decreased, and signaling ing cells via gap junctions at the ends of their processes. cells to adjust ion levels and maintain the adjacent bone matrix Normally the most abundant cells in bone, the almond- accordingly. Lack of exercise (or the weightlessness experi- shaped osteocytes exhibit significantly less RER, smaller Golgi enced by astronauts) leads to decreased bone density, due in complexes, and more condensed nuclear chromatin than part to the lack of mechanical stimulation of these cells. osteoblasts (Figure 8–5a). Osteocytes maintain the calcified FIGURE 8–5 Osteocytes in lacunae. C C b C C a c (a) TEM showing an osteocyte in a lacuna and two dendritic pro- between these structures through which nutrients derived from cesses in canaliculi (C) surrounded by bony matrix. Many such blood vessels diffuse and are passed from cell to cell in living bone. processes are extended from each cell as osteoid is being secreted; (X400; Ground bone) this material then undergoes calcification around the processes, (c) SEM of non-decalcified, sectioned, and acid-etched bone show- giving rise to canaliculi. (X30,000) ing lacunae and canaliculi (C). (X400) (b) Photomicrograph of bone, not decalcified or sectioned, but (Figure 8-5c, used with permission from Dr Matt Allen, Indiana ground very thin to demonstrate lacunae and canaliculi. The lacu- University School of Medicine, Indianapolis.) nae and canaliculi (C) appear dark and show the communication  Types of Bone 143 Osteoclasts released from cells in matrix vesicles promote calcification of the matrix. Other tissues rich in type I collagen lack osteocal- C H A P T E R Osteoclasts are very large, motile cells with multiple nuclei cin and matrix vesicles and therefore do not normally become (Figure 8–6) which are essential for matrix resorption during calcified. bone growth and remodeling. The large size and multinucle- The association of minerals with collagen fibers during ated condition of osteoclasts are due to their origin from the calcification provides the hardness and resistance required for fusion of bone marrow–derived monocytes. Osteoclast devel- bone function. If a bone is decalcified by a histologist, its shape opment requires two polypeptides produced by osteoblasts: is preserved but it becomes soft and pliable like other connec- macrophage-colony–stimulating factor (M-CSF; discussed 8 tive tissues. Because of its high collagen content, decalcified with hemopoiesis, Chapter 13) and the receptor activator of Bone Types of Bone bone matrix is usually acidophilic. nuclear factor-(B ligand (RANKL). In areas of bone undergo- ing resorption, osteoclasts on the bone surface lie within enzy- matically etched depressions or cavities in the matrix known as resorption lacunae (or Howship lacunae). › PERIOSTEUM & ENDOSTEUM In an active osteoclast the membrane domain that con- External and internal surfaces of all bones are covered by con- tacts the bone forms a circular sealing zone which binds nective tissue of the periosteum and endosteum respectively the cell tightly to the bone matrix and surrounds an area with (Figures 8–1a and 8–1c). The periosteum is organized much many surface projections, called the ruffled border. This cir- like the perichondrium of cartilage, with an outer fibrous layer cumferential sealing zone allows the formation of a specialized of dense connective tissue, containing mostly bundled type microenvironment between the osteoclast and the matrix in I collagen, but also fibroblasts and blood vessels. Bundles of which bone resorption occurs (Figure 8–6b). periosteal collagen, called perforating (or Sharpey) fibers, Into this subcellular pocket the osteoclast pumps protons penetrate the bone matrix and bind the periosteum to the to acidify and promote dissolution of the adjacent hydroxy- bone. Periosteal blood vessels branch and penetrate the bone, apatite, and releases matrix metalloproteinases and other carrying metabolites to and from bone cells. hydrolytic enzymes from lysosome-related secretory vesicles The periosteum’s inner layer is more cellular and includes for the localized digestion of matrix proteins. Osteoclast activ- osteoblasts, bone lining cells, and mesenchymal stem cells ity is controlled by local signaling factors from other bone referred to as osteoprogenitor cells. With the potential to cells. Osteoblasts activated by parathyroid hormone produce proliferate extensively and produce many new osteoblasts, M-CSF, RANKL, and other factors that regulate the formation osteoprogenitor cells play a prominent role in bone growth and activity of osteoclasts. and repair. Internally the very thin endosteum covers small trabec- › › MEDICAL APPLICATION ulae of bony matrix that project into the marrow cavities In the genetic disease osteopetrosis, which is characterized (Figure 8–1). The endosteum also contains osteoprogenitor by dense, heavy bones (“marble bones”), the osteoclasts lack cells, osteoblasts, and bone lining cells, but within a sparse, ru%ed borders and bone resorption is defective. This disorder delicate matrix of collagen fibers. results in overgrowth and thickening of bones, often with obliteration of the marrow cavities, depressing blood cell for- › › MEDICAL APPLICATION mation and causing anemia and the loss of white blood cells. Osteoporosis, frequently found in immobilized patients and The defective osteoclasts in most patients with osteopetrosis in postmenopausal women, is an imbalance in skeletal turn- have mutations in genes for the cells’ proton-ATPase pumps over so that bone resorption exceeds bone formation. This or chloride channels. leads to calcium loss from bones and reduced bone mineral density (BMD). Individuals at risk for osteoporosis are rou- tinely tested for BMD by dual-energy x-ray absorptiometry › BONE MATRIX (DEXA scans). About 50% of the dry weight of bone matrix is inorganic mate- rials. Calcium hydroxyapatite is most abundant, but bicarbon- ate, citrate, magnesium, potassium, and sodium ions are also found. Significant quantities of noncrystalline calcium phos- › TYPES OF BONE phate are also present. The surface of hydroxyapatite crystals Gross observation of a bone in cross section (Figure 8–7) shows are hydrated, facilitating the exchange of ions between the a dense area near the surface corresponding to compact (cor- mineral and body fluids. tical) bone, which represents 80% of the total bone mass, and The organic matter embedded in the calcified matrix is 90% deeper areas with numerous interconnecting cavities, called type I collagen, but also includes mostly small proteoglycans and cancellous (trabecular) bone, constituting about 20% of multiadhesive glycoproteins such as osteonectin. Calcium- total bone mass. Histological features and important locations binding proteins, notably osteocalcin, and the phosphatases of the major types of bone are summarized in Table 8–1. 144 CHAPTER 8 Bone FIGURE 8–6 Osteoclasts and their activity. Ocl Ocl Oc B B a Osteoclast Bone matrix Osteoclast Blood capillary Nucleus Golgi Nucleus Vesicles – CO2 + H2O H+ + CH3 Ruffled Section of border circumferential sealing zone Bone matrix Microenvironment of low c b pH and concentrated MMPs Osteoclasts are large multinucleated cells which are derived by the metalloproteases and other hydrolytic enzymes. Acidification of fusion in bone of several blood-derived monocytes. (a) Photo of the sealed space promotes dissolution of hydroxyapatite from bone showing two osteoclasts (Ocl) digesting and resorbing bone bone and stimulates activity of the protein hydrolases, producing matrix (B) in relatively large resorption cavities (or Howship lacu- localized matrix resorption. The breakdown products of collagen nae) on the matrix surface. An osteocyte (Oc) in its smaller lacuna is fibers and other polypeptides are endocytosed by the osteoclast also shown. (X400; H&E) and further degraded in lysosomes, while Ca2+ and other ions are (b) Diagram showing an osteoclast’s circumferential sealing zone released directly and taken up by the blood. where integrins tightly bind the cell to the bone matrix. The sealing (c) SEM showing an active osteoclast cultured on a flat substrate of zone surrounds a ruffled border of microvilli and other cytoplas- bone. A trench is formed on the bone surface by the slowly migrat- mic projections close to this matrix. The sealed space between the ing osteoclast. (X5000) cell and the matrix is acidified to ~pH 4.5 by proton pumps in the (Figure 8–6c, used with permission from Alan Boyde, Centre for ru%ed part of the cell membrane and receives secreted matrix Oral Growth and Development, University of London.)  Types of Bone 145 At the microscopic level both compact and cancellous FIGURE 8–7 Compact and cancellous bone. bone typically show two types of organization: mature lamel- C H A P T E R lar bone, with matrix existing as discrete sheets, and woven bone, newly formed with randomly arranged components. Lamellar Bone Most bone in adults, compact or cancellous, is organized as lamellar bone, characterized by multiple layers or lamel- 8 lae of calcified matrix, each 3-7 )m thick. The lamellae are Bone Types of Bone organized as parallel sheets or concentrically around a cen- tral canal. In each lamella, type I collagen fibers are aligned, with the pitch of the fibers’ orientation shifted orthogonally Compact Cancellous (by about 90 degrees) in successive lamellae (Figure 8–1a). bone bone This highly ordered organization of collagen within lamellar bone causes birefringence with polarizing light microscopy; the alternating bright and dark layers are due to the changing orientation of collagen fibers in the lamellae (Figure 8–8). Like the orientation of wood fibers in plywood the highly Macroscopic photo of a thick section of bone showing the corti- ordered, alternating organization of collagen fibers in lamel- cal compact bone and the lattice of trabeculae in cancellous bone at the bone’s interior. The small trabeculae that make up lae adds greatly to the strength of lamellar bone. highly porous cancellous bone serve as supportive struts, collec- An osteon (or Haversian system) refers to the com- tively providing considerable strength, without greatly increas- plex of concentric lamellae, typically 100-250 )m in diam- ing the bone’s weight. The compact bone is normally covered eter, surrounding a central canal that contains small blood externally with periosteum and all trabecular surfaces of the vessels, nerves, and endosteum (Figures 8–1 and 8–9). cancellous bone are covered with endosteum. (X10) Between successive lamellae are lacunae, each with one osteocyte, all interconnected by the canaliculi containing the cells’ dendritic processes (Figure 8–9). Processes of adjacent In long bones, the bulbous ends—called epiphyses cells are in contact via gap junctions, and all cells of an osteon (Gr. epiphysis, an excrescence)—are composed of cancellous receive nutrients and oxygen from vessels in the central canal bone covered by a thin layer of compact cortical bone. The (Figure 8–1). The outer boundary of each osteon is a layer cylindrical part—the diaphysis (Gr. diaphysis, a growing called the cement line which includes many more noncol- between)—is almost totally dense compact bone, with a thin lagen proteins in addition to mineral and collagen. region of cancellous bone on the inner surface around the cen- Each osteon is a long, sometimes bifurcated, cylinder gen- tral marrow cavity (Figure 8–1). Short bones such as those erally parallel to the long axis of the diaphysis. Each has 5-20 of the wrist and ankle usually have cores of cancellous bone concentric lamellae around the central canal which communi- surrounded completely by compact bone. The flat bones that cates with the marrow cavity and the periosteum. Canals also form the calvaria (skullcap) have two layers of compact bone communicate with one another through transverse perforat- called plates, separated by a thicker layer of cancellous bone ing canals (or Volkmann canals) which have few, if any, con- called the diploë. centric lamellae (Figures 8–1 and 8–10). All central osteonic Table 8–1 Summary of bone types and their organization. Type of Bone Histological Features Major Locations Synonyms Woven bone, newly Irregular and random arrangement of Developing and growing bones; Immature bone; primary bone; calcified cells and collagen; lightly calcified hard callus of bone fractures bundle bone Lamellar bone, Parallel bundles of collagen in thin All normal regions of adult bone Mature bone; secondary bone remodeled from layers (lamellae), with regularly spaced woven bone cells between; heavily calcified Compact bone, ~80% Parallel lamellae or densely packed Thick, outer region (beneath Cortical bone of all lamellar bone osteons, with interstitial lamellae periosteum) of bones Cancellous bone, Interconnected thin spicules or Inner region of bones, adjacent to Spongy bone; trabecular bone; ~20% of all lamellar trabeculae covered by endosteum marrow cavities medullary bone bone 146 CHAPTER 8 Bone FIGURE 8–8 Lamellar bone. FIGURE 8–9 An osteon. C O O CC a L L L L L O I b Osteons (Haversian systems) constitute most of the compact bone. Shown here is an osteon with four to five concentric lamel- lae (L) surrounding the central canal (CC). Osteocytes (O) in lacu- Two photographs of the same area of an unstained section nae are in communication with each other and with the central of compact bone, showing osteons with concentric lamellae canal and periphery of the osteon via through hundreds of den- around central canals. Lamellae are seen only faintly by bright- dritic processes located within fine canaliculi (C). Also shown are field microscopy (a), but they appear as alternating bright and the partial, interstitial lamellae (I) of an osteon that was eroded dark bands under the polarizing light microscope (b). Bright when the intact osteon was formed. (Ground bone; X500) bands are due to birefringence from the highly ordered collagen fibers in a lamella. Alternating bright and dark bands indicate that fibers in successive lamellae have different orientations, an organization that makes lamellar bone very strong. (Both X100) (Used with permission from Dr Matt Allen, Indiana University circumferential lamellae immediately beneath the perios- School of Medicine, Indianapolis.) teum and fewer inner circumferential lamellae around the marrow cavity (Figure 8–1a). The lamellae of these outer and innermost areas of compact bone enclose and strengthen the canals and perforating canals form when matrix is laid down middle region containing vascularized osteons. around areas with preexisting blood vessels. Bone remodeling occurs continuously throughout life. In Scattered among the intact osteons are numerous irreg- compact bone, remodeling resorbs parts of old osteons and pro- ularly shaped groups of parallel lamellae called interstitial duces new ones. As shown in Figure 8–11 osteoclasts remove lamellae. These structures are lamellae remaining from old bone and form small, tunnel-like cavities. Such tunnels are osteons partially destroyed by osteoclasts during growth and quickly invaded by osteoprogenitor cells from the endosteum or remodeling of bone (Figure 8–10). periosteum and sprouting loops of capillaries. Osteoblasts Compact bone (eg, in the diaphysis of long bones) also develop, line the wall of the tunnels, and begin to secrete osteoid includes parallel lamellae organized as multiple external in a cyclic manner, forming a new osteon with concentric FIGURE 8–10 Lamellar bone: Perforating canals and interstitial lamellae. C H A P T E R Interstitial lamellae I I 8 Bone Types of Bone P P First-generation Second-generation Third-generation osteons osteons osteons a b (a) Transverse perforating (Volkmann) canals (P) connecting adja- contributions to the formation of interstitial lamellae. The shading cent osteons are shown in this micrograph of compact lamellar indicates that successive generations of osteons have different bone. Such canals “perforate” lamellae and provide another source degrees of mineralization, with the most newly formed being the of microvasculature for the central canals of osteons. Among the least mineralized. Remodeling is a continuous process that involves intact osteons are also found remnants of eroded osteons, seen as the coordinated activity of osteoblasts and osteoclasts, and is irregular interstitial lamellae (I). (Ground bone; X100) responsible for adaptation of bone to changes in stress, especially (b) Diagram showing the remodeling of compact lamellar during the body’s growth. bone with three generations of osteons and their successive FIGURE 8–11 Development of an osteon. Old bone Forming resorption cavity I Osteoclasts tunneling into Cutting old bone cone Osteoblast Resorption Endothelial cell cavity Reversal zone Mesenchymal cell Growing capillary Newly calcified Closing bone osteon Closing Osteoid cone I Lacunae with osteocytes I Osteon Quiescent osteoblast a b c During remodeling of compact bone, osteoclasts act as a cutting constricted with multiple concentric layers of new matrix, and its cone that tunnels into existing bone matrix. Behind the osteoclasts, lumen finally exists as only a narrow central canal with small blood a population of osteoblast progenitors enters the newly formed vessels. The dashed lines in (a) indicate the levels of the structures tunnel and lines its walls. The osteoblasts secrete osteoid in a cyclic shown in cross section (b). An x-ray image (c) shows the different manner, producing layers of new matrix (lamellae) and trapping degrees of mineralization in osteons and in interstitial lamellae (I). some cells (future osteocytes) in lacunae. The tunnel becomes 148 CHAPTER 8 Bone lamellae of bone and trapped osteocytes (Figures 8–11). In Woven Bone healthy adults 5%-10% of the bone turns over annually. Woven bone is nonlamellar and characterized by random dis- position of type I collagen fibers and is the first bone tissue to › › MEDICAL APPLICATION appear in embryonic development and in fracture repair. Woven bone is usually temporary and is replaced in adults by lamellar The antibiotic tetracycline is a fluorescent molecule that bone, except in a very few places in the body, for example, near binds newly deposited osteoid matrix during mineralization the sutures of the calvaria and in the insertions of some tendons. with high affinity and specifically labels new bone under the In addition to the irregular, interwoven array of collagen UV microscope (Figure 8–12). This discovery led to meth- fibers, woven bone typically has a lower mineral content (it is ods for measuring the rate of bone growth, an important more easily penetrated by x-rays) and a higher proportion of parameter in the diagnosis of certain bone disorders. In one osteocytes than mature lamellar bone. These features reflect technique tetracycline is administered twice to patients, with the facts that immature woven bone forms more quickly but an intervening interval of 11-14 days. A bone biopsy is then has less strength than lamellar bone. performed, sectioned without decalcification, and examined. Bone formed while tetracycline was present appears as fluo- rescent lamellae and the distance between the labeled layers is proportional to the rate of bone appositional growth. This › OSTEOGENESIS Bone development or osteogenesis occurs by one of two procedure is of diagnostic importance in such diseases as processes: osteomalacia, in which mineralization is impaired, and oste- itis fibrosa cystica, in which increased osteoclast activity Intramembranous ossification, in which osteoblasts results in removal of bone matrix and fibrous degeneration. di%erentiate directly from mesenchyme and begin secret- ing osteoid FIGURE 8–12 Tetracycline localization of new bone matrix. a b Newly formed bone can be labeled with tetracycline, which forms (b) reveals active ossification in one osteon (center) and in the fluorescent complexes with calcium at ossification sites and pro- external circumferential lamellae (upper right). vides an in vivo tracer by which newly formed bone can be local- (Used with permission from Dr Matt Allen, Indiana University ized. A group of osteons in bone after tetracycline incorporation in School of Medicine, Indianapolis.) vivo seen with bright-field (a) and fluorescent microscopy  Osteogenesis 149 Endochondral ossification, in which a preexisting Within the condensed mesenchyme bone formation matrix of hyaline cartilage is eroded and invaded by begins in ossification centers, areas in which osteoprogeni- C H A P T E R osteoblasts, which then begin osteoid production. tor cells arise, proliferate, and form incomplete layers of osteo- blasts around a network of developing capillaries. Osteoid The names refer to the mechanisms by which the bone secreted by the osteoblasts calcifies as described earlier, forms initially; in both processes woven bone is produced first forming small irregular areas of woven bone with osteocytes and is soon replaced by stronger lamellar bone. During growth in lacunae and canaliculi (Figure 8–13). Continued matrix of all bones, areas of woven bone, areas of bone resorption, secretion and calcification enlarges these areas and leads to and areas of lamellar bone all exist contiguous to one another. 8 the fusion of neighboring ossification centers. The anatomi- Bone Osteogenesis cal bone forms gradually as woven bone matrix is replaced by › › MEDICAL APPLICATION compact bone that encloses a region of cancellous bone with marrow and larger blood vessels. Mesenchymal regions that Osteogenesis imperfecta, or “brittle bone disease,” refers to a do not undergo ossification give rise to the endosteum and the group of related congenital disorders in which the osteoblasts periosteum of the new bone. produce deficient amounts of type I collagen or defective type In cranial flat bones, lamellar bone formation predominates I collagen due to genetic mutations. Such defects lead to a over bone resorption at both the internal and external surfaces. spectrum of disorders, all characterized by significant fragility Internal and external plates of compact bone arise, while the cen- of the bones. The fragility reflects the deficit in normal colla- tral portion (diploë) maintains its cancellous nature. The fonta- gen, which normally reinforces and adds a degree of resiliency nelles or “soft spots” on the heads of newborn infants are areas to the mineralized bone matrix. of the skull in which the membranous tissue is not yet ossified. Endochondral Ossification Intramembranous Ossification Endochondral (Gr. endon, within + chondros, cartilage) ossi- Intramembranous ossification, by which most flat bones begin fication takes place within hyaline cartilage shaped as a small to form, takes place within condensed sheets (“membranes”) version, or model, of the bone to be formed. This type of ossi- of embryonic mesenchymal tissue. Most bones of the skull and fication forms most bones of the body and is especially well jaws, as well as the scapula and clavicle, are formed embryoni- studied in developing long bones, where it consists of the cally by intramembranous ossification. sequence of events shown in Figure 8–14. FIGURE 8–13 Intramembranous ossification. CM M M O O O B O B M O V V O V M O B O V V M M B B M V P a B b A section of fetal pig mandible developing by intramembranous (b) At higher magnification another section shows these same ossification. (a) Areas of typical mesenchyme (M) and condensed structures, but also includes the developing periosteum (P) adja- mesenchyme (CM) are adjacent to layers of new osteoblasts (O). cent to the masses of woven bone that will soon merge to form Some osteoblasts have secreted matrices of bone (B), the surfaces of a continuous plate of bone. The larger mesenchyme-filled region which remain covered by osteoblasts. Between these thin regions of at the top is part of the developing marrow cavity. Osteocytes in new woven bone are areas with small blood vessels (V). (X40; H&E) lacunae can be seen within the bony matrix. (X100; H&E) 150 CHAPTER 8 Bone FIGURE 8–14 Osteogenesis of long bones by endochondral ossification. Epiphyseal plate Epiphyseal line Articular (remnant of cartilage epiphyseal plate) Epiphyseal Spongy blood vessel bone Hypertrophic cartilage Epiphyseal capillaries Developing Perichondrium periosteum Developing Compact bone Medullary Periosteal compact cavity bone collar bone Primary Medullary ossification cavity Blood center vessel of Periosteum Hyaline periosteal cartilage bud Secondary ossification 1 Fetal hyaline centers cartilage model develops. 2 Cartilage calcifies, Calcified cartilage and a periosteal Epiphyseal bone collar forms plate around diaphysis. 3 Primary ossification center forms in the diaphysis. 4 Secondary ossification centers form in Cancellous bone epiphyses. 5 Bone replaces Epiphyseal line cartilage, except the articular cartilage Articular cartilage and epiphyseal plates. 6 Epiphyseal plates ossify and form epiphyseal lines. This process, by which most bones form initially, begins with undergoes calcification into woven bone, and is then remod- embryonic models of the skeletal elements made of hyaline carti- eled as compact bone. lage (1). Late in the first trimester, a bone collar develops beneath (4) Around the time of birth secondary ossification centers the perichondrium around the middle of the cartilage model, caus- begin to develop by a similar process in the bone’s epiphyses. ing chondrocyte hypertrophy in the underlying cartilage (2). During childhood the primary and secondary ossification centers This is followed by invasion of that cartilage by capillaries gradually come to be separated only by the epiphyseal plate and osteoprogenitor cells from what is now the periosteum to (5) which provides for continued bone elongation. The two ossifi- produce a primary ossification center in the diaphysis cation centers do not merge until the epiphyseal plate disappears (3). Here osteoid is deposited by the new osteoblasts, (6) when full stature is achieved. In this process ossification first occurs within a bone This process in the diaphysis forms the primary ossifi- collar produced by osteoblasts that differentiate within the cation center (Figure 8–14), beginning in many embryonic perichondrium (transitioning to periosteum) around the bones as early as the first trimester. Secondary ossification cartilage model diaphysis. The collar impedes diffusion of centers appear later at the epiphyses of the cartilage model oxygen and nutrients into the underlying cartilage, caus- and develop in a similar manner. During their expansion ing local chondrocytes to swell up (hypertrophy), com- and remodeling both the primary and secondary ossification press the surrounding matrix, and initiate its calcification centers produce cavities that are gradually filled with bone by releasing osteocalcin and alkaline phosphatase. The marrow and trabeculae of cancellous bone. hypertrophic chondrocytes eventually die, creating empty With the primary and secondary ossification centers, two spaces within the calcified matrix. One or more blood ves- regions of cartilage remain: sels from the perichondrium (now the periosteum) pen- etrate the bone collar, bringing osteoprogenitor cells to the Articular cartilage within the joints between long bones (Figure 8–14), which normally persists through adult life porous central region. Along with the vasculature newly formed osteoblasts move into all available spaces and pro- The specially organized epiphyseal cartilage (also called the epiphyseal plate or growth plate), duce woven bone. The remnants of calcified cartilage at which connects each epiphysis to the diaphysis and this stage are basophilic and the new bone is more acido- allows longitudinal bone growth (Figure 8–14). philic (Figure 8–15).  Osteogenesis 151 2. In the proliferative zone, the cartilage cells divide FIGURE 8–15 Cells and matrices of a primary repeatedly, enlarge and secrete more type II collagen and C H A P T E R ossification center. proteoglycans, and become organized into columns par- allel to the long axis of the bone. 3. The zone of hypertrophy contains swollen, terminally di%erentiated chondrocytes which compress the matrix C into aligned spicules and sti%en it by secretion of type X collagen. Unique to the hypertrophic chondrocytes in 8 O developing (or fractured) bone, type X collagen limits dif- Bone Osteogenesis B fusion in the matrix and with growth factors promotes vas- cularization from the adjacent primary ossification center. 4. In the zone of calcified cartilage chondrocytes about to undergo apoptosis release matrix vesicles and osteocalcin to begin matrix calcification by the formation of hydroxy- apatite crystals. 5. In the zone of ossification bone tissue first appears. Cap- C illaries and osteoprogenitor cells invade the now vacant chondrocytic lacunae, many of which merge to form the B initial marrow cavity. Osteoblasts settle in a layer over the O spicules of calcified cartilage matrix and secrete osteoid which becomes woven bone (Figures 8–16 and 8–17). This woven bone is then remodeled as lamellar bone. O In summary, longitudinal growth of a bone occurs by cell proliferation in the epiphyseal plate cartilage. At the same time, B chondrocytes in the diaphysis side of the plate undergo hypertro- phy, their matrix becomes calcified, and the cells die. Osteoblasts lay down a layer of new bone on the calcified cartilage matrix. Because the rates of these two opposing events (proliferation and destruction) are approximately equal, the epiphyseal plate does not change thickness, but is instead displaced away from the center of the diaphysis as the length of the bone increases. A small region of a primary ossification center showing key Growth in the circumference of long bones does not features of endochondral ossification. Compressed remnants involve endochondral ossification but occurs through the of calcified cartilage matrix (C) are basophilic and devoid of chondrocytes. This material becomes enclosed by more activity of osteoblasts developing from osteoprogenitor cells in lightly stained osteoid and woven bone (B) which contains the periosteum by a process of appositional growth which osteocytes in lacunae. The new bone is produced by active begins with formation of the bone collar on the cartilaginous osteoblasts (O) arranged as a layer on the remnants of old diaphysis. As shown in Figure 8–18 the increasing bone cir- cartilage. (X200; Pararosaniline–toluidine blue) cumference is accompanied by enlargement of the central marrow cavity by the activity of osteoclasts in the endosteum. The epiphyseal cartilage is responsible for the growth in length of the bone and disappears upon completion of bone › › MEDICAL APPLICATION development at adulthood. Elimination of these epiphyseal Calcium deficiency in children can lead to rickets, a disease plates (“epiphyseal closure”) occurs at various times with dif- in which the bone matrix does not calcify normally and the ferent bones and by about age 20 is complete in all bones, epiphyseal plate can become distorted by the normal strains making further growth in bone length no longer possible. of body weight and muscular activity. Ossification processes In forensics or through x-ray examination of the growing skel- are consequently impeded, which causes bones to grow eton, it is possible to determine the “bone age” of a young per- more slowly and often become deformed. The deficiency can son, by noting which epiphyses have completed closure. be due either to insufficient calcium in the diet or a failure to An epiphyseal growth plate shows distinct regions of cellular produce the steroid prohormone vitamin D, which is impor- activity and is often discussed in terms of overlapping but his- tant for the absorption of Ca2+ by cells of the small intestine. tologically distinct zones (Figures 8–16 and 8–17), starting with In adults calcium deficiency can give rise to osteomala- the cartilage farthest from the ossification center in the diaphysis: cia (osteon + Gr. malakia, softness), characterized by deficient calcification of recently formed bone and partial decalcifica- 1. The zone of reserve (or resting) cartilage is composed tion of already calcified matrix. of typical hyaline cartilage. 152 CHAPTER 8 Bone FIGURE 8–16 Epiphyseal growth plate: Locations and zones of activity. Zone of reserve cartilage Epiphyseal Epiphyses plates Diaphysis Zone of proliferation Zone of hypertrophy Epiphyses Zone of calcified cartilage Epiphyseal plates Diaphyses Zone of ossification a X-ray of a hand b Epiphyseal plate The large and growing primary ossification center in long bone (b) From the epiphysis to the diaphysis, five general zones have diaphyses and the secondary ossification centers in epiphyses are cells specialized for the following: (1) a reserve of normal hyaline separated in each developing bone by a plate of cartilage called cartilage, (2) cartilage with proliferating chondroblasts aligned as the epiphyseal plate. axial aggregates in lacunae, (3) cartilage in which the aligned cells (a) Epiphyseal plates can be identified in an x-ray of a child’s hand are hypertrophic and the matrix condensed, (4) an area in which as marrow regions of lower density between the denser ossifica- the chondrocytes have disappeared and the matrix is undergoing tion centers. Cells in epiphyseal growth plates are responsible for calcification, and (5) an ossification zone in which blood vessels continued elongation of bones until the body’s full size is reached. and osteoblasts invade the lacunae of the old cartilage, producing Developmental activities in the epiphyseal growth plate occur in marrow cavities and osteoid for new bone. (X100; H&E) overlapping zones with distinct histological appearances. › BONE REMODELING & REPAIR Because it contains osteoprogenitor stem cells in the periosteum, endosteum, and marrow and is very well vas- Bone growth involves both the continuous resorption of bone cularized, bone normally has an excellent capacity for repair. tissue formed earlier and the simultaneous laying down of Bone repair after a fracture or other damage uses cells, new bone at a rate exceeding that of bone removal. The sum signaling molecules, and processes already active in bone of osteoblast and osteoclast activities in a growing bone con- remodeling. Surgically created gaps in bone can be filled with stitutes osteogenesis or the process of bone modeling, which new bone, especially when periosteum is left in place. The maintains each bone’s general shape while increasing its mass. major phases that occur typically during bone fracture repair The rate of bone turnover is very active in young children, include initial formation of fibrocartilage and its replace- where it can be 200 times faster than that of adults. In adults ment with a temporary callus of woven bone, as shown in the skeleton is also renewed continuously in a process of bone Figure 8–19. remodeling which involves the coordinated, localized cellu- lar activities for bone resorption and bone formation shown in the diagram of Figure 8–11. The constant remodeling of bone ensures that, despite its › › MEDICAL APPLICATION hardness, this tissue remains plastic and capable of adapting Bone fractures are repaired by a developmental process involv- its internal structure in the face of changing stresses. A well- ing fibrocartilage formation and osteogenic activity of the major known example of bone plasticity is the ability of the positions bone cells (Figure 8–19). Bone fractures disrupt blood vessels, of teeth in the jawbone to be modified by the lateral pressures causing bone cells near the break to die. The damaged blood produced by orthodontic appliances. Bone forms on the side vessels produce a localized hemorrhage or hematoma. Clotted where traction is applied and is resorbed on the opposite side blood is removed along with tissue debris by macrophages and where pressure is exerted. In this way, teeth are moved within the matrix of damaged, cell-free bone is resorbed by osteoclasts. the jaw while the bone is being remodeled.  Metabolic Role Of Bone 153 FIGURE 8–17 Details of the epiphyseal growth plate. C H A P T E R R H H P H GP H C 8 H H C C C Bone Metabolic Role Of Bone C C M C M M C B M B C M C b B a M B (a) At the top of the micrograph the growth plate (GP) shows its (b) Higher magnification shows more detail of the cells and matrix zones of hyaline cartilage with chondrocytes at rest (R), proliferat- spicules in the zones undergoing hypertrophy (H) and ossification. ing (P), and hypertrophying (H). As the chondrocytes swell they Staining properties of the matrix clearly change as it is compressed release alkaline phosphatase and type X collagen, which initiates and begins to calcify (C), and when osteoid and bone (B) are laid hydroxyapatite formation and strengthens the adjacent calcifying down. The large spaces between the ossifying matrix spicules spicules (C) of old cartilage matrix. The tunnel-like lacunae in which become the marrow cavity (M), in which pooled masses of eosino- the chondrocytes have undergone apoptosis are invaded from philic red blood cells and aggregates of basophilic white blood cell the diaphysis by capillaries that begin to convert these spaces into precursors can be distinguished. Still difficult to see at this magni- marrow (M) cavities. Endosteum with osteoblasts also moves in fication is the thin endosteum between the calcifying matrices and from the diaphyseal primary ossification center, covering the spic- the marrow. (X100; H&E) ules of calcified cartilage and laying down layers of osteoid to form a matrix of woven bone (B). (X40; H&E) The periosteum and the endosteum at the fracture site › METABOLIC ROLE OF BONE respond with intense proliferation and produce a soft callus Calcium ions are required for the activity of many enzymes of fibrocartilage-like tissue that surrounds the fracture and and many proteins mediating cell adhesion, cytoskeletal move- covers the extremities of the fractured bone. ments, exocytosis, membrane permeability, and other cellular The fibrocartilaginous callus is gradually replaced in functions. The skeleton serves as the calcium reservoir, con- a process that resembles a combination of endochondral taining 99% of the body’s total calcium in hydroxyapatite crys- and intramembranous ossification. This produces a hard tals. The concentration of calcium in the blood (9-10 mg/dL) callus of woven bone around the fractured ends of bone. and tissues is generally quite stable because of a continuous Stresses imposed on the bone during repair and interchange between blood calcium and bone calcium. during the patient’s gradual return to activity serve to The principal mechanism for raising blood calcium remodel the bone callus. The immature, woven bone of the levels is the mobilization of ions from hydroxyapatite to callus is gradually resorbed and replaced by lamellar bone, interstitial fluid, primarily in cancellous bone. Ca2+ mobili- remodeling and restoring the original bone structure. zation is regulated mainly by paracrine interactions among bone cells, many of which are not well understood, but two 154 CHAPTER 8 Bone FIGURE 8–18 Appositional bone growth Compact bone Periosteum Bone deposited by osteoblasts Medullary Periosteum Bone resorbed cavity by osteoclasts Medullary cavity Compact bone Infant Child Young adult Adult Bones increase in diameter as new bone tissue is added beneath radial bone growth formation of new bone at the periosteal the periosteum in a process of appositional growth. Also called surface occurs concurrently with bone removal at the endosteal radial bone growth, such growth in long bones begins with forma- surface around the large medullary, enlarging this marrow-filled tion of the bone collar early in endochondral ossification. During region and not greatly increasing the bone’s weight. FIGURE 8–19 Main features of bone fracture repair. Fibro- cartilaginous (soft) callus Medullary Compact bone Primary at fracture site cavity bone Hematoma Hard callus Periosteum Regenerating Compact bone blood vessels 1 A fracture hematoma forms. 2 A fibrocartilaginous 3 A hard (bony) callus forms. 4 The bone is remodeled. (soft) callus forms. Repair of a fractured bone occurs through several stages but uti- procallus is invaded by regenerating blood vessels and proliferat- lizes the cells and mechanisms already in place for bone growth ing osteoblasts. In the next few weeks the fibrocartilage is gradu- and remodeling. (1) Blood vessels torn within the fracture release ally replaced by woven bone which forms a hard callus throughout blood that clots to produce a large fracture hematoma. (2) This the original area of fracture. (4) The woven bone is then remodeled is gradually removed by macrophages and replaced by a soft as compact and cancellous bone in continuity with the adjacent fibrocartilage-like mass called procallus tissue. If torn by the break uninjured areas and fully functional vasculature is reestablished. the periosteum reestablishes its continuity over this tissue. (3) The  Joints 155 polypeptide hormones also target bone cells to influence cal- Syndesmoses join bones by dense connective tissue cium homeostasis: only. Examples include the interosseous ligament of the C H A P T E R inferior tibiofibular joint and the posterior region of the Parathyroid hormone (PTH) from the parathyroid sacroiliac joints. glands raises low blood calcium levels by stimulating osteoclasts and osteocytes to resorb bone matrix and Symphyses have a thick pad of fibrocartilage between the thin articular cartilage covering the ends of the release Ca2+. The PTH e%ect on osteoclasts is indirect; bones. All symphyses, such as the intervertebral discs PTH receptors occur on osteoblasts, which respond by and pubic symphysis, occur in the midline of the body. secreting RANKL and other paracrine factors that stimu- 8 late osteoclast formation and activity. Intervertebral discs (Figure 8–20) are large sym- Bone Joints Calcitonin, produced within the thyroid gland, can physes between the articular surfaces of successive bony reduce elevated blood calcium levels by opposing the e%ects of PTH in bone. This hormone directly targets osteoclasts to slow matrix resorption and bone turnover. FIGURE 8–20 Intervertebral disc. › › MEDICAL APPLICATION In addition to PTH and calcitonin, several other hormones act on bone. The anterior lobe of the pituitary synthesizes growth hormone (GH or somatotropin), which stimulates the liver to produce insulin-like growth factor-1 (IGF-1 or somatomedin). IGF has an overall growth-promoting effect, especially on the BM epiphyseal cartilage. Consequently, lack of growth hormone during the growing years causes pituitary dwarfism; an excess of growth hormone causes excessive growth of the long bones, resulting in gigantism. Adult bones cannot increase in length even with excess IGF because they lack epiphyseal cartilage, but they do increase in width by periosteal growth. In adults, an increase in GH causes acromegaly, a disease in which the bones—mainly the long ones—become very thick. AF AF › › MEDICAL APPLICATION NP In rheumatoid arthritis chronic inflammation of the synovial membrane causes thickening of this connective tissue and stimulates the macrophages to release collagenases and other hydrolytic enzymes. Such enzymes eventually cause destruction of the articular cartilage, allowing direct contact of the bones projecting into the joint. › JOINTS Joints are regions where adjacent bones are capped and held together firmly by other connective tissues. The type of joint determines the degree of movement between the bones. Joints classified as synarthroses (Gr. syn, together + arthrosis, articulation) allow very limited or no movement and are sub- divided into fibrous and cartilaginous joints, depending on Section of a rat tail showing an intervertebral disc and the the type of tissue joining the bones. Major subtypes of synar- two adjacent vertebrae with bone marrow (BM) cavities. The disc consists of concentric layers of fibrocartilage, comprising throses include the following: the annulus fibrosus (AF), which surrounds the nucleus pulp- Synostoses involve bones linked to other bones and osus (NP). The nucleus pulposus contains scattered residual cells of the embryonic notochord embedded in abundant allow essentially no movement. In older adults synosto- gel-like matrix. The intervertebral discs function primarily as ses unite the skull bones, which in children and young shock absorbers within the spinal column and allow greater adults are held together by sutures, or thin layers of mobility within the spinal column. (X40; PSH) dense connective tissue with osteogenic cells. 156 CHAPTER 8 Bone vertebral bodies. Held in place by ligaments these discoid components of the intervertebral joints cushion the bones › › MEDICAL APPLICATION and facilitate limited movements of the vertebral column. Within an intervertebral disc, collagen loss or other degenera- Each disc has an outer portion, the annulus fibrosus, con- tive changes in the annulus fibrosus are often accompanied by sisting of concentric fibrocartilage laminae in which colla- displacement of the nucleus pulposus, a condition variously gen bundles are arranged orthogonally in adjacent layers. called a slipped or herniated disc. This occurs most frequently The multiple lamellae of fibrocartilage produce a disc with on the posterior region of the intervertebral disc where there are unusual toughness able to withstand pressures and torsion fewer collagen bundles. The affected disc frequently dislocates generated within the vertebral column. or shifts slightly from its normal position. If it moves toward Situated in the center of the annulus fibrosus, a gel- nerve plexuses, it can compress the nerves and result in severe like body called the nucleus pulposus allows each disc to pain and other neurologic disturbances. The pain accompany- function as a shock absorber (Figure 8–20). The nucleus ing a slipped disc may be perceived in areas innervated by the pulposus consists of a viscous fluid matrix rich in hyaluro- compressed nerve fibers—usually the lower lumbar region. nan and type II collagen fibers, but also contains scattered, vacuolated cells derived from the embryonic notochord, the only cells of that structure to persist postnatally. The Joints classified as diarthroses permit free bone move- nucleus pulposus is large in children, but these struc- ment. Diarthroses (Figure 8–21) such as the elbow and knee tures gradually become smaller with age and are partially generally unite long bones and allow great mobility. In a diar- replaced by fibrocartilage. throsis ligaments and a capsule of dense connective tissue FIGURE 8–21 Diarthroses or synovial joints. Periosteum Yellow bone marrow SM Fibrous layer