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What are the general features of cartilage?
- avascular specialized fibrous connective tissue.
- firm extracellular matrix
- Three types: Hyaline, elastic, fibrocartilage
What are the components of hyaline cartilage?
- Matrix, perichondrium, chondroblast, chondrocyte
What is the feature of matrix of hyaline cartilage?
- amorphous ground substance containing proteoglycan aggregates and chondronectin, in which type II collagen is embedded The matrix that is adjacent to chondrocytes is called the territorial matrix. This part of the matrix is poor in collagen but rich in proteoglycans
Major collagen of Bone and cartilage is .... and ...........
What are the features of Perichondrium?
- Surrounds hyaline cartilage except at articular surfaces.
- It consists of an outer fibrous layer containing type I collagen, fibroblasts, and blood vessels and an inner cellular layer containing chondrogenic cells and chondroblasts.
- It provides the nearest blood supply to the avascular cartilaginous tissue.
................manufacture the cartilage
Mesenchymal cells can be induced to become secreting chondroblasts in the proper environment, but if removed and grown as a monolayer in a low-density substrate, they will ................
discontinue secreting cartilage matrix, become fibroblastlike, and secrete type I rather than type II collagen
What are chondrocytes?
Once chondroblasts become totally enveloped by matrix, they are referred to as chondrocytes
Which carilage type primarily contain type I collagen?
What are the locations for each types of cartilage?
- Hyaline--> Articular ends of long bones, nose, larynx, trachea, bronchi, ventral ends of ribs, template for endochondral bone formation
- Elastic--> Pinna of ear, auditory canal and tube, epiglottis, some laryngeal cartilages
- Fibrocartilage--> Intervertebral discs, articular discs, pubic symphysis, insertion of tendons, meniscus of knee
Which cartilage lack perichondrium?
What are the two types of histogenesis of hyaline cartilage?
- Interstitial growth results from cell division of preexisting chondrocytes. This type of growth occurs only during the early stages of cartilage formation and in articular cartilage and the epiphyseal plates of long bones.
- Appositional growth results from differentiation of chondrogenic cells in the perichondrium. This type of growth results in the formation of chondroblasts and/or new chondrocytes, which elaborate a new layer of cartilage matrix at the periphery
Which hormones diminish cartilage histogenesis?
Cortisone, hydrocortisone, estradiol
Which hormones enhance cartilage histogenesis?
Thyroxine, testosterone, somatotropin
How does vitamin A affect cartilage?
- Hypovitaminosis A: Diminishes thickness of epiphyseal plates.
- Hypervitaminosis A: Accelerates ossification of epiphyseal plates.
How does vitamin C and D affect cartilage?
- Hypovitaminosis C: Stops matrix production, distorts cartilage columns in epiphyseal plates; scurvy develops.
- Hypovitaminosis D: Deficient absorption of calcium and phosphorus: epiphyseal cartilage cells proliferate, but matrix fails to calcify, and growing bones become deformed; rickets develops
What are the features of elastic cartilage?
- Identical to hyaline cartilage except for a network of elastic fibers, which impart a yellowish color.
- Although it contains type II collagen, it is less prone to degeneration than hyaline cartilage and is located in areas where flexible support is required.
What are the features of fibrocartilage?
- lacks an identifiable perichondrium.
- It is characterized by alternating rows of fibroblast-derived chondrocytes surrounded by scant matrix and thick parallel bundles of type I collagen fibers.
- Fibrocartilage is located in areas where support and tensile strength are required.
Applied pressure results in bone ............
Applied tension results in bone ............
What is the component of bone matrix?
- Inorganic (65%)--> hydroxyapatite crystals, which have the composition Ca10(PO4)6(OH)2
- Organic (35%)--> type I collagen (95%), chondroitin sulfate and keratan sulfate, Osteocalcin and osteopontin, both glycoproteins, Bone sialoprotein
What are the glycoproteins of bone?
What is the function of osteocalcin and osteonectin?
bind to hydroxyapatite and also bind to integrins on osteoblasts and osteoclasts
.................. is a matrix protein that also binds to integrins of the osteoblasts and osteocytes and is thus related to adherence of bone cells to bone matrix
What are the features of periosteum?
- Bone external surfaces, except at synovial articulations and muscle attachments.
- It is composed of an outer dense fibrous collagenous layer and an inner cellular osteoprogenitor (osteogenic) layer.
- Sharpey fibers (type I collagen) attach the periosteum to the bone surface.
- The periosteum functions to distribute blood vessels to bone.
- The endosteum is a thin specialized connective tissue that lines the marrow cavities and supplies osteoprogenitor cells and osteoblasts for bone growth and repair.
At low O2 tension osteoprogenitors change to ..............
Where is the place for osteoprogenitor cells?
periosteum and the endosteum
What are the factors that contribute to formation of osteoblasts from osteoprogenitors?
bone morphogenic protein (BMP) family and alsotransforming growth factor–β
PTH receptor in the bone is on.......
What are the products of osteoblasts?
- Osteoblasts are responsible for the synthesis of organic protein components of bone matrix, including type I collagen, proteoglycans, and glycoproteins, which they secrete asosteoid (uncalcified bone matrix).
- Macrophage colony-stimulating factor (M-CSF)
- Receptor for the activation of nuclear factor Kappa B (RANKL)
- Osteocalcin (for bone mineralization),
- Osteopontin (for formation of sealing zone between osteoclasts and the subosteoclastic compartment)
- Osteonectin (related to bone mineralization),
- Bone sialoprotein (binding osteoblasts to extracellular matrix).
Osteoblasts produce...........for formation of sealing zone between osteoclasts and the subosteoclastic compartment
How do osteoblasts and osteocytes interact via processes?
By gap junction
What is osteocyte?
- Osteocytes are mature bone cells housed in their own lacunae
- They have narrow cytoplasmic processes that extend through canaliculi in the calcified matrix
- They contain abundant heterochromatin, a paucity of RER, and a small Golgi complex (unlike osteoblasts)
What are the receptors on the surface of osteoclasts?
colony-stimulating factor-1 receptor, calcitonin receptor; and RANK (nuclear factor kappa B).
How does PTH and calcitonin affect osteoblastic and clastic activity?
Osteoblasts that have been stimulated by PTH promote osteoclast formation, whereas osteoblasts that have been stimulated by calcitonin inhibit osteoclast formation by stimulating osteoid synthesis and calcium deposition
What are the three signals from osteoblast that affect osteclast function?
- osteoclast precursors (macrophages) are stimulated by M-CSF to undergo mitosis.
- Another signaling molecule, RANKL, binds to the precursor, inducing it to differentiate into the multinucleated osteoclast, thus activating it to commence bone resorption.
- A third signal, osteoprotegerin (OPG), a member of the tumor necrosis factor receptor (TNFR) family produced by osteoblasts and other cells, can prohibit RANKL from binding to the macrophage, thus prohibiting osteoclast formation
Cytoplasm of osteoblast and osteoclast are........ and ............
What is the main function of osteoclast?
Osteoclasts function in the resorption of bone (osteolysis). They form and reside in depressions known as Howship's lacunae, which represent areas of bone resorption.
What is the morphology of osteoclasts?
- Osteoclasts display four regions in electron micrographs.
- Basal zone houses most of the organelles of the osteoclast and is the farthest from the subosteoclastic compartment
- The ruffled border is the site of active bone resorption. It is composed of irregular fingerlike cytoplasmic projections extending into the subosteoclastic compartment, a slight depression that deepens as the osteoclast resorbs bone and then that depression is referred to as Howship's lacuna.
- The clear zone surrounds the ruffled border. It contains actin filaments at the periphery that help osteoclasts maintain contact with the bony surface and isolates the region of osteolytic activity. Osteopontin, secreted by osteoblasts, is used to seal the zone between osteoclasts and the subosteoclastic compartment.
- The vesicular zone contains exocytotic vesicles that transfer lysosomal enzymes to Howship's lacunae and endocytotic vesicles that transfer degraded bone products from Howship's lacunae to the interior of the cell.
What are the stages of bone resorption?
- Osteoclasts secrete acid, which decalcifies the surface layer of bone.
- Acid hydrolases, collagenases, and other proteolytic enzymes secreted by osteoclasts then degrade the organic portion of the bone.
- Osteoclasts resorb the organic and inorganic residues of the bone matrix and release them into connective tissue capillaries
Osteopetrosis is a disorder .....................
in which osteoclasts do not possess ruffled borders--> impaired bone resorption
What are the two types of bone on gross observation?
- Spongy (cancellous) bone, which is composed of interconnected trabeculae. Bony trabeculae surround cavities filled with bone marrow. The trabeculae contain osteocytes and are lined on both surfaces by a single layer of osteoblasts. Spongy bone is always surrounded by compact bone.
- Compact (dense) bone has no trabeculae or bone marrow cavities.
What are the two types of bone based on microscopic view?
- Primary bone, also known as immature or woven bone: Primary bone contains many osteocytes and large, irregularly arranged type I collagen bundles.It has a low mineral content.It is the first compact bone produced during fetal development and bone repair.It is remodeled and replaced by secondary bone except in a few places (e.g., tooth sockets, near suture lines in skull bones, and at insertion sites of tendons).
- Secondary bone, is also known as mature or lamellar bone: Secondary bone is the compact bone of adults.It has a calcified matrix arranged in regular layers, or lamellae. Each lamella is 3 to 7 µm thick.It contains osteocytes in lacunae between, and occasionally within, lamellae
What is the organization of lamella in compact bone?
- Haversian systems (osteons)
- Interstitial lamella
- Outer and inner circumferential lamellae
What are haversian systems?
- Haversian systems (osteons) are long cylindrical structures that run approximately parallel to the long axis of the diaphysis.Haversian systems are composed of 4 to 20 lamellae surrounding a central haversian canal, which contains blood vessels, nerves, and loose connective tissue.
- They are lined by osteoprogenitor cells and osteoblasts.
- They are often surrounded by an amorphous cementing substance.
- They are interconnected by Volkmann canals, which also connect to the periosteum and endosteum and carry the neurovascular supply
- Interstitial lamellae are irregularly shaped lamellae between haversian systems
- Outer and inner circumferential lamellae are located at the external and internal surfaces of the diaphysis
How is intramembranous bone formation done?
- 1) Intramembranous bone formation is the process by which most of the flat bones (e.g., parietal bones of the skull) are formed.
- 2) It involves the following events: Mesenchymal cells, in the presence of a vascular zone, condense into primary ossification centers, differentiate into osteoblasts, and begin secreting osteoid.
- 3) As calcification occurs, osteoblasts become trapped in their own matrix and become osteocytes. These centers of developing bone are called trabeculae (fused spicules).
- 4) Fusion of the bony trabeculae produces spongy bone as blood vessels invade the area and other undifferentiated mesenchymal cells give rise to the bone marrow.
- 5) The periosteum and endosteum develop from portions of the mesenchymal layer that do not undergo ossification
- 6)Mitotic activity of the mesenchymal cells gives rise to osteoprogenitor cells, which undergo cell division and form more osteoprogenitor cells or differentiate into osteoblasts within the inner layer of the developing periosteum.
- forming haversian canals (fHC), osteoblasts (Ob), and osteocytes (arrows).
What is enchondral bone formation?
- Endochondral bone formation is the process by which long bones are formed. It begins in a segment of hyaline cartilage that serves as a small model for the bone.
- The two stages of endochondral bone formation involve the development of primary and secondary centers of ossification
What are the steps of enchondral bone formation?
- (A) Endochondral bone formation requires the presence of a hyaline cartilage model. (B) Vascularization of the diaphysis perichondrium (2) results in the transformation of chondrogenic cells to osteogenic cells, hence formation via intramembranous bone formation of a subperiosteal bone collar (1) that quickly becomes perforated by osteoclastic activity. Chondrocytes in the center of the cartilage hypertrophy (3) and their lacunae become confluent. (C) The subperiosteal bone collar (1) increases in length and width. The confluent lacunae are invaded by the periosteal bud (4). Osteoclastic activity forms a primitive marrow cavity (5) whose walls are composed of calcified cartilage—calcified bone complex. The epiphyses display the beginning of secondary ossification centers (7). (D and E) The subperiosteal bond collar (1) is now large enough to support the developing long bone, so that much of the cartilage has been resorbed except for the epiphyseal plate (8) and the covering of the epiphyses (9). Ossification in the epiphyses occurs from the center (10); thus, the vascular periosteum (11) does not cover the cartilaginous surface. Blood vessels (12) enter the epiphyses, without vascularizing the cartilage, to constitute the vascular network (13) around which spongy bone will form
What are the steps in primary enchondral bone formation?
- The primary center of ossification develops at the midriff of the diaphysis of the hyaline cartilage model by the following sequence of events:
- Vascularization of the perichondrium at this site causes the transformation of chondrogenic cells to osteoprogenitor cells, which differentiate into osteoblasts. This region of the perichondrium is now called the periosteum.
- Osteoblasts elaborate matrix deep to the periosteum, and via intramembranous bone formation, form the subperiosteal bone collar.
- Chondrocytes within the core of the cartilaginous model undergo hypertrophy and degenerate, and their lacunae become confluent, forming large cavities (eventual marrow spaces).
- Osteoclasts create perforations in the bone collar that permit the periosteal bud (blood vessels, osteoprogenitor cells, and mesenchymal cells) to enter the newly formed spaces in the cartilaginous model.The cartilage that constitutes the walls of these spaces then becomes calcified.
- Newly developed osteoblasts elaborate bone matrix that becomes calcified on the surface of the calcified cartilage, forming a calcified cartilage–calcified bone complex. In histological sections, the calcified cartilage stains basophilic, whereas the calcified bone stains acidophilic.
- The subperiosteal bone collar becomes thicker and elongates toward the epiphysis.
- Osteoclasts begin to resorb the calcified cartilage–calcified bone complex, thus enlarging the primitive marrow cavity.
- Repetition of this sequence of events results in bone formation spreading toward the epiphyses
How does secondary centers of ossification develop?
- Secondary centers of ossification develop at the epiphyses in a sequence of events similar to that described for the primary center, except a bone collar is not formed.
- Development of these centers begins when osteoprogenitor cells invade the epiphysis and differentiate into osteoblasts, which elaborate bone matrix to replace the disintegrating cartilage.
- When the epiphyses are filled with bone tissue, cartilage remains in two areas, the articular surfaces and the epiphyseal plates.
- Articular cartilage persists and does not contribute to bone formation.
- Epiphyseal plates continue to grow by adding new cartilage at the epiphyseal end while it is being replaced with bone at the diaphyseal end (lengthening the bone).
- Ossification of the epiphyseal plates and cessation of growth occur at about 20 years of age.
primary center of ossification develops at the......................
midriff of the diaphysis
..................... of the perichondrium at primary ossification center causes the transformation of chondrogenic cells to osteoprogenitor cells, which differentiate into osteoblasts.
How does osteoblasts form subperiosteal bone collar?
intramembranous bone formation
How does marrow space form in enchondral bone formation?
Chondrocytes within the core of the cartilaginous model undergo hypertrophy and degenerate, and their lacunae become confluent, forming large cavities (eventual marrow spaces).
How does perisoteal bud performs in enchondral bone formation?
Osteoclasts create perforations in the bone collar that permit the periosteal bud (blood vessels, osteoprogenitor cells, and mesenchymal cells) to enter the newly formed spaces in the cartilaginous model
In membranous bone formation osteoblasts are derived from...............
What is the requirement for mesenchymal cells to become osteoblasts in intramembranous bone formation?
presence of a vascular zone
Which cell is the origin of the osteoprogenitor cells in enchondral bone formation?
How does secondary ossification center form?
Development of these centers begins when osteoprogenitor cells invade the epiphysis and differentiate into osteoblasts, which elaborate bone matrix to replace the disintegrating cartilage. When the epiphyses are filled with bone tissue, cartilage remains in two areas, the articular surfaces and the epiphyseal plates.
What is the arrangement of zones of the epiphyseal plates?
- The zone of reserve cartilage is at the epiphyseal side of the plate. It possesses small, randomly arranged inactive chondrocytes.
- The zone of proliferation (of chondrocytes) is a region of rapid mitotic divisions giving rise to rows of isogenous cell groups.
- The zone of cell hypertrophy and maturation is the region where the chondrocytes are greatly enlarged.
- The zone of calcification is the region where hypertrophied chondrocytes die and the cartilage becomes calcified.
- The zone of ossification is the area where newly formed osteoblasts elaborate bone matrix on the calcified cartilage, forming a calcified cartilage–calcified bone complex, which is resorbed and replaced by bone.
How does bone calcify?
- Osteonectin, proteoglycans, and bone sialoprotein, are known to stimulate calcification.
- Matrix vesicles, released by osteoblasts, contain high concentrations of calcium Ca2+ and PO432 ions along with several other organic compounds and enzymes.
- Calcium pumps in the matrix membranes bring in more calcium, concentrating it and forming calcium hydroxyapatite crystals that grow and eventually puncture the matrix vesicle expelling its contents.
- Calcium hydroxyapatite crystals that become free in the matrix become nidi of crystallization.
- Released enzymes free phosphate ions that unite with the calcium forming calcium phosphate.
- Calcium phosphate then begins to calcify the matrix around the nidi of crystallization.
- Water is removed from the matrix permitting hydroxyapatite crystals to be deposited into gaps within the collagen fibrils.
- Nidi of mineralization, enlarge, fuse with neighboring nidi eventually calcifying the entire matrix
How is bone remodeled?
- Early on, bone development outpaces bone resorption as new haversian systems are added and fewer are resorbed.
- Later, when the epiphyseal plates are closed, ending bone growth, bone development, and resorption are balanced.
- Several factors, including calcitonin and PTH, are responsible for this phenomenon regarding compact bone. Remodeling of cancellous bone is under the control of many factors within the bone marrow
Bone remodeling in compact bone is under control of .............
PTH and calcitonin
Bone remodeling in cancellous bone is under control of ..............
Factors within bone marrow
How is fractured bone repaired?
- A bone fracture damages the matrix, bone cells, and blood vessels in the region and is accompanied by localized hemorrhaging and blood clot formation.
- Proliferation of osteoprogenitor cells occurs in the periosteum and endosteum in the vicinity of the fracture. As a result of this proliferation, cellular tissue surrounds the fracture and penetrates between the ends of the damaged bone.
- Formation of a bony callus occurs both internally and externally at a fracture site.Fibrous connective tissue and hyaline cartilage are formed in the fracture zone.
- Endochondral bone formation replaces the cartilage with primary bone.
- Intramembranous bone formation also produces primary bone in the area.
- The irregularly arranged trabeculae of primary bone join the ends of the fractured bone, forming a bony callus.The primary bone is resorbed and replaced with secondary bone as the fracture heals.
What are the role of vitamins in bone formation?
- Vitamin D is necessary for absorption of calcium from the small intestine. Vitamin D deficiency results in poorly calcified (soft) bone, a condition known as rickets in children and osteomalacia in adults. Vitamin D is also necessary for bone formation (ossification), whereas an excess of vitamin D causes bone resorption.
- Vitamin A deficiency inhibits proper bone formation and growth, whereas an excess accelerates ossification of the epiphyseal plates. Deficiency or excess of vitamin A results in small stature.
- Vitamin C is necessary for collagen formation. Deficiency results in scurvy, characterized by poor bone growth and inadequate fracture repair
What are the features of rickets and osteomalacia?
- Rickets: deficient calcification in newly formed bone and is generally accompanied by deformation of the bone spicules in epiphyseal plates
- Osteomalacia: deficient calcification in newly formed bone and decalcification of already calcified bone
What are the effects of hormone on bone formation?
- Parathyroid hormone activates osteoblasts to secrete osteoclast-stimulating factor, which then activates osteoclasts to resorb bone, thus elevating blood calcium levels.
- Calcitonin eliminates the ruffled border of osteoclasts and inhibits bone matrix resorption, preventing the release of calcium.
- GH It stimulates overall growth, especially that of epiphyseal plates, and influences bone development via insulinlike growth factors (somatomedins), especially stimulating growth of the epiphyseal plates.
What are the two types of joints?
- Synarthroses are immovable joints composed of connective tissue, cartilage, or bone. These joints unite the first rib to the sternum and connect the skull bones to each other.
- Diarthroses (synovial joints) permit maximum movement and generally unite long bones. These joints are surrounded by a two-layered capsule, enclosing and sealing the articular cavity. The articular cavity contains synovial fluid, a colorless, viscous fluid that is rich in hyaluronic acid and proteins.
What is the composition of joint capsule?
- The external (fibrous) capsular layer is a tough, fibrous layer of dense connective tissue.
- The internal (synovial) capsular layer is also called the synovial membrane.
- It is lined by a layer of squamous to cuboidal epithelial cells on its internal surface. Two cell types are displayed in electron micrographs of this epithelium.Type A cells are intensely phagocytic and have a well-developed Golgi complex, many lysosomes, and sparse RER. Type B cells resemble fibroblasts and have a well-developed RER; these cells probably secrete synovial fluid
Haversian canals are interconnected via ........................