Bone Formation PDF

BONE FORMATION—Sabiston cartilage; perichondrium develops around cartilage model - Ossification - Process of bone formation; b. Growth of c...

BONE FORMATION—Sabiston cartilage; perichondrium develops around cartilage model - Ossification - Process of bone formation; b. Growth of cartilage model - Occurs in four principal situations: - Chondroblast is deeply buried in cartilage ECM then ✓ Initial formation of embryo chondrocytes—grows in length by cell ✓ Growth of bones during infancy, childhood, & division(Interstitial growth adolescence ✓ Remodelling of bone c. Development of primary ossification center ✓ Repair of fractures d. Development of medullary cavity e. Development of secondary ossification center f. Formation of articular cartilage INITIAL BONE FORMATION Embryonic skeleton initially composed of BONE—Janquiera mesenchyme, where cartilage formation and ossification occur during 6th week. Bone formation follows two patterns: 1) Intramembranous Ossification - Bone forms directly from the mesenchyme—arranged in sheetlike layers w/c resembles membrane; - Flat bone of skill, facial bone, mandible, medial part of clavicle (collar) forms this way; Steps in intramembranous ossification: a. Development of ossification Center - Chemical messages; mesenchyme clusters & differentiates into osteoprogenitor cells then osteoblasts—secretes org. ECM - Ossification Center: Site of cluster b. Calcification - Secretion of ECM stops then becomes osteocyctes - Ca & Mineral salts deposited and ECM hardens & calcifies c. Formation of trabeculae Bone tissues provide: - ECM forms then becomes trabeculae then fuse into ✓ Support spongy bone around network of blood vessels. CT ✓ Protection—vital organs associates with it and differentiates into red bone ✓ Cavities—bone marrow marrow ✓ Reservoir—Ca, Phosphate, ✓ Lever—multiplies force d. Development of Periosteum - Mesenchyme condenses at periphery of bone Three major cell type: develops into periosteum. - Thin layer of compact bone replaces surface layer of spongy bone but spongy bone remains in the center; - Newly formed bone is remodelled (destroyed and reformed) as bone adult size and shape 2) Endochondral Ossification - Bone forms within hyaline cartilage that develops from mesenchyme; - Replacements of cartilage by bone Proceed as follows: a. Development of cartilage model - Mesenchyme is triggered by chemical messages to crowd then develops into chondroblast which secretes cartilage ECM—cartilage model: hyaline  BONE RESORPTION EXCEEDS BONE FORMATION 1. Osteocytes-found in cavities, lacunae - Osteoblast then become Osteocyte: enclosed in lacunae; - Osteocyte communicates with on another via canaliculi - With less RER, Smaller Golgi, more condensed nuclear chromatin - Maintains bony matrix and death—rapid matrix resorption; - Produces sclerostin and cytokine then regulates bone remodelling - Involved in Ca homeostasis and sensor for mechanical Bone Matrix stresses on bone ---→ bone remodelling Inorganic Materials 50%: Hydroxyapatite is most 2. Osteoblasts – synthesize organic component of ECM abundant but HCO3, Ca, Mg, K are also present. - From osteoprogenitor cells -→ Osteoblast—produce Organic: embedded in calcified matrix—type 1 osteoid— collagen type I, proteoglycans and matrix collagen, proteoglycan, aggregates, bone specifin vesicles -→ Osteocyte multiadhesive glycoprotein (osteonectin). Ca binding - Active: cuboidal to columnar shape and basophilic osteocalcin and phosphatase released in matrix vesicle cytoplasm; Inactive: Size flattens; represent most of by osteoblast promotes calcification of matrix. flattened bone lining cells in both endosteum and Abraham: Chondroitin Sulfate, Keratan Sulfate, periosteum. Hyluronic acid, and noncollagenous proteins, - Appositional Growth: matrix -→new layer, osteoid synthesized by osteoblast includes Osteocalcin, Osteopontin (anchors osteoclast to bone by formation (not calcified); this process is completed by deposition of sealing zone before resorption), Osteonectin (binds of Ca salts into newly formed matrix-→ Osteocytes with type 1 collagen and hydroxyapatite). (monocyte) trapped inlacunae (once it’s calcified) Osteocalcin and Osteopontin -→ increased - Osteoblast—osteocalcin and glycoprotein-→ binds stimulation with active Vitamin D metabolite, 1a,25- with Ca dihydroxycholecalciferol. - Osteoblast—matrix vesicles (rich in alkaline phosphatase and other enzymes-→raises PO4 All bones are lined on both internal and external by CT - With O concentration of Ca and phosphate-→ w/c contains endosteum on internal and periosteum on formation ofhydroxyapatite crystals w/c is first visible in external. calcification. Periosteum 3. Osteoclast-Multinucleated, giant cells involved in - Outer layer is dense connective tissue c small blood resorption and remodelling of bone tissue; vessels, collagen bundles, and fibroblast. - Large, motile cells c multiple nuclei (d/t origin from Perforating (sharpey) fibers-→penetrates bone fusion of bone marrow-derived cells) and involved in matrix—binding periosteum to bone; resorption during bone and remodelling. - Inner region contains osteoblast and mesenchymal - Development requires M-CSF and receptor activator stem cell— osteoprogenitor cells factor of RANKL. Lies within Howship Lacunae. - Principal function: Nourishes osseous tissue and - Active: surface against bone matrix—folded into continuous supply of new osteoblast for irregular projections, ruffled border surrounded by appositional bone growth and repair; cytoplasmic zone rich in actin filaments—site of adhesion to matrix. Endosteum - Secretes collagenase, cathepsin K and enzymes, - Covers trabeculae; Thinner tan periosteum but pumps protons—creates acidic environment -→ contains osteoprogenitor cells, osteoblast, and bone degradation ofhydroxyapatite and promotes digestion lining cells of matrix proteins - With receptors for calcitonin and thyroid hormone; - Osteoporosis: lacks ruffled borders and bone Types of Bone resorption is defective -→ overgrowth and thickening of bone—obliterates marrow cavities - →anemia and loss of WBC; Osteoclasts has mutated proton-ATPase pumps or chloride channels;  condensation of mesenchymal tissue—within condensed layer is the starting point for bone LAMELLAR WOVEN formation (ossific. center) - Organized around central canal -Non-lamellar; random - Mesenchymal Cell→osteoprogenitor cell— - Each lamella—type I collagen disposition of type I proliferates and form incomplete layer of osteoblast - Osteon(Haversian System): collagen fibers and first around network of developing capillaries; concentric lamella surrounding bone tissue to appear in - Polarized osteoblast—secretes osteoid components small central canal c blood embryonic development vessels, nerves, loose CT, and and in fracture repair; that calcify and forms trabeculae of woven bone. endosteum; -Temporary and replaced in - Continued matrix secretion, calcification, trabecular - Transverse (Volkmann adults— except in calvaria growth Canal)— marrow cavity and insertion of some - —fusion of ossification centers and produce layers of communicates c periosteum tendons; compact bone—encloses a region of cancellous bone - Interstitial Lamella—lamellae -Lower mineral content c marrow and larger vessels; remaining from osteon partially with higher - Two layers of compact bone (internal and external destroyed by osteoclasts proportion of during osteoclasts—forms plates (arise; central portion (diploe) maintain its growth and remodelling of bone; quickly; cancellous, spongy nature. 2. Endochondral Ossification OSTEOGENESIS - Pre-existing matrix of hyaline cartilage is eroded and invaded by osteoblast → begins osteoid production. ▪ Takes place within piece of hyaline cartilage—shape resembles a small version of bone to be formed; ▪ First bone tissue appears as collar that surrounds diaphysis of cartilage mode. Bone collar—produced by activity of osteoblasts—forms surrounding perichondrium; ▪ Chondrocyte→produce alkaline phosphatase and swell → enlarges lacunae—compresses matrix into narrow trabeculae leads to calcification; ▪ Death of chondrocytes→porous structure with calcified cartilage remnants covered by osteoblasts. ▪ Blood vessel from perichondrium(periosteum)— penetrates bringing osteoprogenitor cells; Osteoblasts then adheres and produce woven bone. ▪ Primary Ossification—process in diaphysis→ beginning in many bones in first trimester; ▪ Secondary Ossification Centers—appears later at epiphyses of cartilage model; Steps of endochondral ossification: 1. Later in 1st trimester: Collar develops beneath perichondrium around middle age of bone; Causes degeneration of underlying cartilage; 2. Invasion of degenerating cartilage by capillaries and osteoprogenitor cells—degeneration of underlying cartilage. 3. Degenerated cartilage—invasion of capillaries and osteoprogenitor cells; deposition of primary ossification center. Osteoid is deposited by new osteoblasts, calcification and remodelled as compact bone; 4. Birth by secondary ossification center—develops similar with epiphyses; Bone development/osteogenesis involves two processes: 5. Provide continued bone elongation do not merge until 1. Intramembranous Ossification ephiphyseal plate provides continued bone elongation. 6. Epiphyseal plate—continued bone elongation - Osteoblast differentiate directly from mesenchyme— secretes osteoid; - Most flat bones begin to form; takes place within  FRACTURE HEALING 1. Blood vessel torn within fracture→releases blood clots →forms large hematoma 2. Replaced by macrophage with soft fibrocartilage- like mass of procallus tissue rich in collage and fibroblast 3. Soft procullas invaded by regrowing blood vessels and osteoblasts. Fibrocartilage is replaced by trabeculae—forming hard callus 4. Woven bone is remodelled as compact and cancellous bone in continuity with adjacent uninjured areas and fully functional vasculature is reeastablished. Two regions of cartilage remain: Articular Cartilage—within joints; persist thru adult life Epiphyseal Cartilage—epiphyseal plate, connects epiphysis to diaphysis; responsible for growth in length and disappears at adulthood→bone growth ceases; Epiphyseal growth plate in five zones: 1. Resting Zone— with hyaline cartilage with typical chondrocytes; 2. Proliferative Zone—chondrocytes divide rapidly→columns of stacked cells parallel to long bones; 3. Hypertrophic Cartilage Zone—swollen, degenerative chondrocytes whose cytoplasm has accumulated glycogen —compresses matrix into thin septa between chondrocytes; 4. Calcified Cartilage Zone—loss of chondrocytes by apoptosis c calcification of septa →forming hydroxyapatite crystals; 5. Ossification Zone—bone tissue first appears; Capillaries and Osteoprogenitor cells from periosteum invades cavities; cavities merges→marrow cavity; Osteoblast settle in a layer over septa of calcified cartilage matrix and secrete osteoid→Woven bone. Growth in length of bone occurs by proliferation of chondrocytes in epiphyseal plate. Chondrocyte at diaphyseal side hypertrophy→matrix becomes METABOLIC ROLE OF BONE calcified and cells die. Osteoblast lay down a new Calcium ion—cell adhesion, cytoskeletal layer of bone movements, exocytosis, membrane permeability; - Principal mechanism for raising blood Ca level→ mobilization of ions from hydroxyapatite crystals to interstitial fluid mainly in cancellous bone; Two hormones influence Ca homeostasis: Parathyroid Hormone Calcitonin - Acts in bone—raise low blood - Synthesized within Ca by stimulating osteoclasts parathyroid; Macroscopic Structure of Mature Bone and osteocyte → resorb - Reduce elevated blood Ca Two forms of bone can be distinguished: matrix and release Ca; - Directly targets - PTH receptor on osteoblasts— osteoclasts—slow matrix 1. Compact/Dense Bone responds by secreting resorption and bone - Long bone, shaft or diaphysis forms central marrow paracrine turnover; space— marrow cavity factors→ stimulates osteoclasts 2. Spongy/Trabecular/Cancellous - Network if bony spicules/trabeculae delimiting spaces - Ends of long bones, epiphyses; JOINTS - Epiphysis is separated c diaphysis via epiphyseal plate— connected to diaphysis by spongy bone. - Bones are capped and held together firmly by connective - Metaphysis connects diaphysis and epiphysis tissues. - Movement between bone are determined by the type of joint. Cellular Bone Components 1. Osteoblast Synarthroses - Initiate and control mineralization of osteoid. - Allows limited or no movement; subdivided into - Release type 1 collagen, Osteocalcin, Osteopontin, fibrous and cartilaginous joints; major subtypes are the Osteonectin and as well as cytokines. following: a. Synostoses—bones are united only by bone tissues; no 2. Osteoclasts movement; unites skull bones (adult) and sutures - Not derived from mesenchyme lineage but to (young adults and children) monocyte precursor originated from bone marrow; b. Syndesmoses—joined by connective tissue only. - Monocyte—blood circulation fuse into Interosseous ligament of inferior tibiofibrular joint and multinucleated c as many as 30 nuclei to form post region of sacroiliac joint. osteoclasts by a process regulated by osteoblasts c. Symphyses—immobile joints with pad of (Osteoclastogenesis); fibrocartilage; all occurs in the midline of body. Three essential functions: Diarthroses ✓ Bone remodelling—removal and replacement of new bone - Permits free movement—elbow and knee unites long ✓ Proper shaping of bone bones and allow great mobility. Ligaments and capsule ✓ Extension of medullary spaces to enable of dense CT maintains proper alignment of bones. Joint hematopoieses; cavity—contains synovial fluid; lined by synovial - Found in compact bone within haversian canals and membrane—secretes synovial fluid—from blood surface of cancellous bone; plasma with hyaluronan - Rich in mitochondria, acidified vesicles and coated vesicles Synovial membrane contains two specialized cells: 1. Type A cells (Macrophage-like synovial cells) - Derived from monocytes and remove wear-and- tear debris; - Regulates inflammatory events 2. Type B cells (Fibroblastic Synovial Cells) - Produce hyaluronan and EC component; - Transported by water from capillaries → synovial fluid— lubricates joint, reducing friction, supplies nutrients and oxygen - Intervertebral disc—allows limited vertebral mobility and consists of large pads of fibrocartilage—cushion; - Intervertebral disc consist mainly by nucleus polposus and annulus fibrosus;