Cartilage and Bone PDF

Chapter 7 - Cartilage: Cartilage is a tough, resilient type of connective tissue that structurally supports certain soft tissues, notably in the respiratory tract, and provides cushioned, low friction surfaces in joints. Cells of cartilage, chondrocytes, make up a small percentage of the tissue’s m...

Chapter 7 - Cartilage: Cartilage is a tough, resilient type of connective tissue that structurally supports certain soft tissues, notably in the respiratory tract, and provides cushioned, low friction surfaces in joints. Cells of cartilage, chondrocytes, make up a small percentage of the tissue’s mass, which is mainly a flexible mass of extracellular matrix (ECM). 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. Cartilage always lacks blood vessels, lymphatics and nerves, but usually has a surrounding dense connective tissue perichondrium that is vascularized. There are three major forms of cartilage: 1. hyaline cartilage 2. elastic cartilage 3. fibrocartilage. Hyaline Cartilage The ECM of hyaline cartilage appears homogenous and glassy, rich in fibrils of type II collagen and aggrecan complexes with bound water. The ECM has less collagen and more proteoglycan immediately around the lacunae, producing slight staining differences in this territorial matrix. Chondrocytes occur singly or in small, mitotically derived isogenous groups. Perichondrium is usually present, but not with hyaline cartilage of articular surfaces or the epiphyses of growing long bones. Elastic Cartilage 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. Elastic cartilage provides flexible support for the external ear as well as certain structures of the middle ear and larynx; it always includes the surrounding perichondrium. Fibrocartilage Fibrocartilage contains varying combinations of hyaline cartilage in variable amounts of dense connective tissue. Histologically it consists of small chondrocytes in a hyaline matrix, usually layered with larger areas of bundled type I collagen with scattered fibroblasts. Fibrocartilage provides very tough, strong support at tendon insertions and in intervertebral discs and certain other joints. Cartilage Formation, Growth, & Repair All forms of cartilage develop from embryonic mesenchyme. 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 or replacement of injured cartilage occurs very slowly and ineffectively, due in part to the tissue’s avascularity and low metabolic rate. Chapter 8 - Bone: Bone tissue provides solid support for the body, protects organs and encloses internal cavities containing bone marrow where blood cells form. Bones, also called osseous tissues, also serve as a reservoir of calcium, phosphate and other minerals, storing or releasing these ions in a controlled fashion to maintain constant concentrations. Components of bone: Three key cell types: osteocytes, osteoblasts and osteoclasts > typically in lamellar organization of bone. Osteocytes - become localized in cavities (lacunae) between bone matrix layers (lamellae) with cytoplasmic processes in small canaliculi, extending into the matrix Osteoblasts - growing cells, which synthesize and secrete the organic components of the matrix Osteoclasts - giant, multinucleated cells involved in removing calcified bone matrix and remodeling bone tissue Bone tissue: A combination of pale-staining mesenchymal regions containing capillaries, fibroblasts and osteoprogenitor stem cells, and variably darker blue regions of normally calcified matrix with varying amounts of collagen and the three cell types. Bone-forming osteoblasts 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. When osteoids undergo calcification and harden, they also entrap osteoblasts which will differentiate to osteocytes that occupy the lacunae surrounded by bony matrix. Osteoclasts, which are produced by fusion of blood monocytes, reside on bony surfaces and erode the matrix during bone remodeling. Exchanges between osteocytes and blood capillaries depend on communication through a very thin, cylindrical space of canaliculi.  Both the internal and external surfaces of all bones have covering of connective tissue containing osteogenic cells, called endosteum (internally surrounding the marrow cavity) and periosteum (on the other surface). Osteoblasts: Produce organic components, also osteonectin (matricellular glycoproteins). Active osteoblasts occur at bone matrix surfaces, bound by integrins and form a single layer of cuboidal cells joined by adherent and gap junctions. Some osteoblasts differentiate, after completing their synthetic activity, as osteocytes entrapped in matrix-bound lacunae, others flatten and cover the matrix surface as bone lining cells, and majority undergo apoptosis. Matrix synthesis and calcification with osteoblasts: Osteoblasts occur as polarized cells, have ultrastructural features, denoting active protein synthesis and secretion. Secreting matrix components at the cell surface in contact with existing bone matrix, osteoblasts produce a layer of unique collagen-rich material called osteoid between the cuboidal cell layer and the preexisting bone surface. The most prominent protein secreted is vitamin K-dependent polypeptide osteocalcin, which binds calcium ions. Osteoblasts also release membrane-enclosed matrix vesicles rich in alkaline phosphatase that raises local conc of phosphate ions. Medical application: Cancer directly from bone cells is uncommon, but one called osteosarcoma can arise in osteoprogenitor cells. In the skeleton, that's the site of these metastatic tumors, but arises when cancer cells move into bones via small blood or lymphatic vessels from malignancies in other organs. Osteocytes: Become surrounded by the material they secrete and then differentiate as osteocytes singly within the lacunae spaced throughout the mineralized matrix. During the period that they mature from osteoblast to osteocytes, the cells extend many long dendritic processes that also become surrounded by calcifying matrix. These processes come to occupy the many canaliculi. Exchange of metabolites between osteocytes and blood vessels occur through the small amounts of interstitial fluid in the lacunae and canaliculi between bone matrix and the osteocytes and their processes. These osteocytes processes form an extensive lacunar - canalicular network that allows osteocytes to serve as mechanosensors detecting the mechanical load on the bone, as well as stress-or-fatigue induced microdamage, and also trigger remedial activity in osteoblasts and osteoclasts. Osteocytes have less RER, smaller golgi and more condolences nuclear chromatin than osteoblasts. Osteocytes maintain the calcified matrix and their death causes progressive resorption of adjacent matrix. Osteocytes express many different proteins, including factors with endocrine and paracrine > helps regulate bone remodeling. Medical application: Resistance exercise can produce increased bone density and thickness in affected regions, whilst lack of exercise leads to decreased bone density, due in part to the lack of mechanical stimulation of the bone cells. Osteoclasts: Develop as very large, multinucleated motile cells, important for matrix resorption during bone growth and remodeling. Their development requires two polypeptide factors produced by osteoblasts: macrophage-colony-stimulating factor (M-CSF), and receptor activator of nuclear factor. Osteoclasts lie on the bone surface within enzymatically etched depressions or cavities in the matrix known as resorption lacunae, in bones undergoing resorption. There is a place in active osteoclasts called sealing zone where integrins tightly bind the cell to the bone matrix. The sealing zone surrounds a ruffled border of microvilli and other cytoplasmic projections close to this matrix. Acidification of sealed space promotes dissolution from bone and stimulates activity of the protein hydrolases, producing localized matrix resorption. The breakdown products of collagen fibers and other polypeptides undergo endocytosis by osteoclasts and degradation in lysosomes, while calcium ions are released directly and taken up by the blood. Medical application: Osteopetrosis - dense, heavy bones. Osteoclasts lack ruffled borders and resorption is defective. Results in overgrowth and thickening of bones. Causing anemia and loss of white blood cells. The defective osteoclasts have mutations in genes for the cells’ proton-ATPase pumps or chloride channels. Bone matrix: Inorganic materials make up 50%. Type I collagen comprises 90% of the organic matter embedded in the calcified matrix, which also includes small proteoglycans and multiadhesive such as osteonectin. Calcium-binding proteins (feks osteocalcin) promote calcification of the matrix. Decalcified bone matrix usually appears as acidophilic. Periosteum & endosteum: Connective tissue layers. Periosteum - outer fibrous layer containing bundled type I collagen, fibroblasts and blood vessels. Bundles of periosteal collagen, called perforating fibers, become embedded in the bone matrix and bind the periosteum to the bone. Branches of periosteal canals are also surrounded by matrix and carry metabolites to and from deeper regions of the bone. Inner, highly cellular, layer of the periosteum is called osteoprogenitor cells. Internally, the thin endosteum covers small trabeculae of bony matrix that project into the marrow cavities. Contains osteoprogenitor cells, osteoblasts and bone lining cells. Medical application: Osteoporosis freq. in immobilized patients and postmenopausal women, from imbalance in skeletal turnover so bone resorption exceeds bone formation > calcium loss and reduced bone mineral density. Types of bone: - Woven bone, newly calcified - irregular and random arrangements of cells and collagen. In developing and growing bones. Immature bone - Lamellar bone - remodeled from woven bone - parallel bundles of collagen in thin layers. has regularly spaced cells between. In all regions of normal bones. Mature bone. - Compact bone - parallel lamellae or densely packed osteons, with interstitial lamellae. Thicker, outer region of bones. Cortical bone. - Cancellous bone - interconnected thin spicules or trabeculae covered by endosteum. Inner region of bones. Spongy bone. Long bones: - Bulbous ends are called epiphyses. covered by a thin region of trabecular cancellous bone on the inner surface. Short bones: - cores of cancellous bones surrounded by compact bone Flat bones: - have two layers of compact bone called plates, separated by a thicker layer of cancellous bone called diploe. Osteon: complex of concentric lamellae, surrounding a central canal that contains small blood vessels, nerves and endosteum. Outer layer called cement line. Mostly compact bones. Long, bifactured, cylinders generally parallel to the long axis of diaphysis. Types of lamellae: - Interstitial lamellae > remains of osteons partially destroyed by osteoclasts during growth and remodeling - External circumferential lamellae > beneath periosteum in compact bone - Inner circumferential lamellae > around marrow cavity Osteogenesis: Bone development > occurs by one of two processes: Intramembranous ossification: osteoblasts differentiate directly from mesenchyme and begin secreting osteoid. Takes place in condensed sheets of embryonic mesenchymal tissue. Bone formation begins in ossification centers, where osteoprogenitor cells arise, proliferate and form incomplete layers of osteoblasts around a network of developing capillaries. Continued matrix secretion and calcification enlarges these areas and leads to fusion of neighboring ossification centers. Regions that don't ossification give rise to endosteum and periosteum of new bone. Endochondral ossification: Pre pre-existing matrix of hyaline cartilage becomes eroded and invaded by osteoblasts, triggering osteoid production. Forms most bones of the body, especially long bone formation. Steps: Late in first trimester > bone collar develops beneath perichondrium > chondrocytes hypertrophy in underlying cartilage Invasion of cartilage by capillaries and osteoprogenitor cells from what is now periosteum to produce primary ossification center Around birth: secondary ossification centers begin to develop Childhood > two processes become separated by epiphyseal plate > bone elongation. Two regions of cartilage remains after this:  - Articular cartilage: in joints between long bones - Epiphyseal cartilage: connects epiphysis (tip of long bone) to diaphysis (shaft) and allows longitudinal bone growth Medical application: Osteogenesis imperfecta > osteoblasts produce deficient amounts of type I collagen due to genetic mutations > fragility of bones > deficit in normal collagen Epiphyseal growth - zones and their activities: 1. Zone of reserve cartilage > typical hyaline cartilage 2. Proliferative zone > cells divide repeatedly, organized into columns and then enlarge to secrete more type II collagen 3. Zone of hypertrophy > swollen, differentiated chondrocytes. Type X collagen in fractured bone limits diffusion 4. Zone of calcified cartilage > chondrocytes about to undergo apoptosis 5. Zone of ossification > bone tissue first appearsInvasion by osteoprogenitor cells and capillaries. Woven bone > lamellar bone. Growth in long bone does not involve endochondral ossification but occurs through activity of osteoblasts developing from osteoprogenitor cells in the periosteum by a process of appositional growth > bone increases in diameter as a new bone tissue beneath the periosteum. Medical application: Calcium deficiency in children > rickets > bone matrix does not calcify normally and the epiphyseal plate can become distorted. Bone grows slowly, because of impeded ossification processes. In adults > osteomalacia > decalcification of recently formed bone and partial decalcification of already calcified matrix. Bone remodeling and repair: Bone growth > continuous resorption of bone tissue formed earlier and laying of new bone. Sum of osteoblasts and osteoclast activities in a growing bone > osteogenesis. Bone turnover rate > very active in children (upto 200 times faster than in adults) Bone remodeling ensures that the tissue remains plastic and capable of adapting its internal structure in the face of changing stresses. Bone repair after fracture etc, uses cells, signaling molecules and processes already active in bone remodeling. Metabolic role of bone: Calcium ions > cellular functions, Skeleton > calcium reservoir > 99% of bodys total calcium in hydroxyapatite crystals. Raising blood calcium levels involves mobilization of ions from hydroxyapatite to interistal fluids > cancellous bone. Polypeptide hormones that target bone cells to influence calcium homeostasis: - Parathyroid hormone > from the parathyroid glands raises low blood calcium levels by stimulating osteoclasts and osteocytes > resorb bone matrix and release calcium-ions. Appears on osteoblasts - Calcitonin > in thyroid gland reduces elevated blood calcium levels by opposing effects of PTH in bone. Directly targets osteoclasts to slow matrix resorption and bone turnover. Medical application: Rheumatoid arthritis > chronic inflammation of synovial membrane > thickening of connective tissue > destruction of articular cartilage. Joints: Skeletal regions where adjacent bones become capped and firmly held together by other connective tissue. Type of joint determines movement, Synarthroses - limited or no movements - Synostoses: bones linked to other bones and allow essentially no movement - Syndesmoses: bones by dense connective tissues - Symphyses: thick pad of fibrocartilage between thin articular cartilage covering ends of bones. In midline of body Intervertebral discs > large symphyses between articular surfaces if successive bony vertebral bodies. Held in place by ligaments. Outer portion: annulus fibrosus > concentric fibrocartilage laminae Center portion: nucleus pulposus > gel-like body. Gives function of shock-absorber. Displacement of this > slipped or herniated disc. Diarthroses - free bone movement Unite ling bones and allow great mobility. The capsule encloses a sealed joint cavity containing synovial fluid (lined by synovial membrane). Area of synovial membrane maintains two specialized cells with distinctly different function and origins: - Macrophage-like type A cells: from blood monocytes and remove wear-and tear debris from synovial fluid - Fibroblastic synovial cells type B cells: lubricates joints, reducing friction