logging in or signing up Bone biology drpriyam Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1393 Category: Education License: All Rights Reserved Like it (7) Dislike it (0) Added: October 19, 2009 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: redrose1 (14 month(s) ago) thanx Saving..... Post Reply Close Saving..... Edit Comment Close By: kaipei (15 month(s) ago) Good and Comprehensive contents about bone biology Saving..... Post Reply Close Saving..... Edit Comment Close By: f_sharaby (19 month(s) ago) good lecture please, send a copy thx Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Bone biology : Bone biology By Priyam Mishra First year PG Dept of Periodontics & Implantology Sree Balaji dental college Chennai Introduction : Introduction Rigid organs They function - move, support & protect Made mostly of collagen, bone is a living & growing, mineralized tissue. Serves 2 primary functions: -structural support -calcium metabolism Classification : Classification A: - According to position -axial : bones forming the axis of skeleton Eg – skull, ribs, sternum & vertebrae. -appendicular: bones forming the skeleton of limbs. Slide 4: B:- According to size & shape -Long bones : present in upper & lower limbs. Eg – humerus, radius, ulna etc. -Short long bones : eg – Metacarpals, Metatarsals & Phalanges -Short bones : Eg – Carpal & Tarsal bones Slide 5: Short long bones Long bones Slide 6: Short bones Slide 7: -Flat bones : Protect vital structures & provide extensive areas for muscular attachment. Eg – Scapula, Sternum, Ribs, Parietal & Frontal bones -Irregular bones : eg – vertebrae & some skull bones. Slide 8: -Pneumatic bones : flat or irregular bones possessing a hollow space within the body which contains air. Eg – Ethmoid & Maxilla. -Sesamoid bones : do not possess periosteum & Haversian systems. Ossify after birth. Eg- Pisiform & Patella (largest in Femoris Quadriceps). : C:- According to gross structure -Compact bone or lamellar bone : Outer cortical part of long bones. Hard & homogenous in appearance. Gives protection, support & resist stress. -Trabecular bone : Accounts for 20% of total bone mass. Eg – flat, short & irregular bones. Slide 10: -Diploic bone : Has inner & outer tables of Compact bone with an intervening porous layer. Eg – most of Cranial bones. -Accessory bones: Failure of normal ossification centre to fuse to main part of bone or appearance of an extra ossification centre may both simulate a fracture on x-ray. Eg- a persistent Metopic suture. Slide 11: D:- According to development -Membranous bones : develop in membrane. -Cartilaginous (endochondral) bones : develop in cartilage. functions : functions Protection shape Blood production Growth factor storage Endocrine organ Detoxification Sound transduction Fat storage Mineral storage Movement Acid-base balance Composition : Composition Bone is composed of 2/3 of inorganic matter & 1/3 of organic matter. Inorganic part : Calcium & Phosphates – 95% Magnesium Trace elements – Ni, Fe, Cd, F, Zn & Molybdenum. Slide 14: Organic part : Collagen – 88-90% (type I) Non collagenous substances – 10-11% Glycoproteins – 6-9% Proteoglycans – 0.8% Sialoproteins – 0.35% Lipids – 0.4% Non-collagenous proteins : Non-collagenous proteins Osteocalcin : inhibits mineralization : recruits bone cell precursors Osteonectin or SPARC : facilitates type I collagen mineralization : suppresses rate of hydroxyapatite crystal growth : modulates cell attachment & deattachment Slide 16: Osteopontin : cell binding activity :osteoclast anchoring activity :mineral binding activity Bone sialoprotein : cell binding activity Bone proteoglycan II (Decorin) : binds to collagen fibre : regulate fibre growth : binds or presents growth factors in matrix Slide 17: Thrombospondin : cell attachment : binds & organizes matrix Matrix gla-protein : prevents growth plate mineralization Latent TGF-β1binding protein 1 : storage of latent TGF-β1 BLOOD SUPPLY : BLOOD SUPPLY Circulus articularis vasculosis : supply the epiphysis & metaphysis. Nutrient artery anastomoses with numerous metaphyseal & epiphyseal arteries. Periosteal vessels supply outer third of cortex. Medullary vessels, inner two-thirds of cortex. Lymphatics & nerve supply : Lymphatics & nerve supply Found accompanying vascular plexus. Nerves are distributed freely within periosteum & accompany blood vessels. Found in interior of bone in perivascular spaces of Haversian canals. osteogenesis : osteogenesis Development of bone : Development of bone Development involves : -Endochondral ossification -Intramembranous ossification -Sutural ossification Slide 22: The process by which bone tissue replaces membranous fibrous tisssue : Intramembranous ossification. Eg, flat bones of Calvarium. Diaphysis increase in width throughout postnatal growth. Intrmembranous ossification : Intrmembranous ossification Area of mesenchyme prior to mesenchymal condensation Slide 24: Cells are closely packed to form mesenchymal condensation Slide 25: Collagen fibres are laid down between mesenchymal cells Slide 26: osteoblasts Bundle of collagen fibres Slide 27: osteiod Slide 28: Osteiod converted to lamella of bone Endochondral ossification : Endochondral ossification Involves replacement of cartilaginous model by bone. Occur in long bones, Femur & Humerus. Also called Intercartilaginous ossification. Slide 31: Sequence of ossification includes : Primary ossification centre : -takes place in centre of future bone shaft. -cartilage cells hypertrophy & cartilage matrix becomes calcified. Bone collar : -cells of perichondrium begins to form bone. -collar holds together shaft, weakened by cartilage disintegration. Slide 33: Periosteal buds : -connective tissue buds or sprouts containing mesenchymal cells & vessels. -grow from periosteum to reach primary ossification centre. -osteoblasts produce osteoid. Slide 34: Secondary ossification centres : -about time of birth, appears in each end of long bone. -cartilage between centres , called Epiphyseal plate. -Epiphyseal line : union point of ossification centres. Slide 36: Five zones of cartilage are associated with endochondral ossification : Zone of reserve cartilage- large zone & typical hyaline cartilage Zone of cell proliferation- small cells arranged in columns, indicates mitotic activity Slide 37: Zone of cell & lacunar maturation & hypertrophy enlargement- chondrocytes increase in size & resorb lacunar wall Zone of calcification- small zone, chondrocytes die here Zone of cartilage removal & bone deposition Cartilage zones : Cartilage zones Sutural ossification : Sutural ossification Play important role in growing face & skull. Fibrous joints between bones. Function : to permit the skull & face to accommodate growing organs such as eyes & brain. Slide 40: At the suture, the outer layer of periosteum splits into :outermost leaf :innermost leaf The outermost leaf unites with the outermost leaf of other side. The inner leaf, called Capsule along with cambium runs down the suture. Same osteogenic potential as periosteum. Structure of bone : Structure of bone Can be described as : -Macroscopic structure -Microscopic structure -Molecular structure Macroscopic structure : Macroscopic structure Based on porosity, there can be : -dense cortical tissue -spongy cancellous tissue CORTICAL BONE : CORTICAL BONE Cortical or compact bone 85% of total bone in body. Found in shafts of long bones & forms a shell around vertebral bodies & other spongy bones. Haversian system Compact bone : Compact bone Trabecular bone : Trabecular bone 15% of total bone Found in cuboidal & flat bones & in the ends of long bones. Bone matrix in the form of plates called Trabeculae. Medullary cavities : has red & yellow marrow Slide 49: Mature or adult bones consist of lamellae or microscopic layers. Three distinct types are : Circumferential Concentric Interstitial Slide 50: Circumferential lamellae : enclose the entire adult bone, forming its outer perimeter. Concentric lamellae : make up the bulk of compact bone & form the basic metabolic unit of bone, the Osteon. Interstitial lamellae : interspersed between adjacent concentric lamellae & fill the spaces between them. osteon : osteon Basic metabolic unit of bone Is a cylinder of bone, parallel to the long axis of the bone. In the centre has haversian canal which is lined by a single layer of bone cells; each canal houses a capillary. Adjacent canals are connected by Volkmann canals, creating a rich vascular network. periosteum : periosteum Except for the articular surfaces, the outer surface of bone is covered with Periosteum. Site of considerable - metabolic - cellular - biomechanical activities Slide 55: Composed two layers of specialized connective tissue. The outer fibrous layer - dense collagenous fibres & fibroblasts. The inner cellular or Cambium layer, is in direct contact with bone, contains functional osteoblasts. Slide 56: Has various functions: -acts as a medium of attachment -nutrition -presence of Osteoprogenitor cells -fibrous layer or Limiting layer endosteum : endosteum Medullary cavities & spaces are covered by Endosteum. It’s a thin delicate membrane consisting of a single layer of osteoblasts. Its architecturally similar to Cambium layer of Periosteum. Microstructure : Microstructure Four types of bone : - woven - composite - lamellar - bundle Woven bone : Woven bone Plays a principle role in healing Forms very quickly, approximately 30 to 60 mm/day. Disorganized Soft Slide 60: Can be more mineralized than Lamellar bone, helps to compensate for its lack of organization. Composite bone : Composite bone Refers to the transitional state between Phase I bone & Lamellar (phase II) bone. A Woven bone lattice filled with Lamellar bone can be seen. Lamellar bone : Lamellar bone Most abundant mature , load bearing bone in the body. Extremely strong Forms slowly, approximately 0.6 to 1mm/day Well organized collagen protein & mineralized structure with multiple layers. Slide 63: Haversian system Haversian canal Interstitial system Bundle bone : Bundle bone Principle bone found around ligaments & joints. Consists of striated interconnections with ligaments. Molecular structure : Molecular structure Bone is made up of : - type I collagen -water -hydroxyapatite material -proteoglycans -non collagenous proteins Collagen - tensile strength & flexibility -place for the nucleation of bone mineral crystal -rigidity & strength Slide 66: Organic portion : - occupies 35% of matrix - formed by osteocollagenous fibres. These are joined by a cement like substance that consists of Glucosaminoglycan (protein-polysaccharide). Slide 67: Inorganic component : - comprises 65% of bone weight - localized only in the interfibrinous cement. Minerals : mainly hydroxyapatite crystals. Also contains Carbonate, Fluoride, Proteins & Peptides. Other components such as BMP, regulate how bone is laid down & maintained Slide 68: Bone matrix has sequential layers, varying in thickness from 300 to 700 microns. Result of rhythmic & uniform matrix deposition. Bone cells : Bone cells Cells of bone are : Osteoblasts Osteocytes Osteoclasts Bone lining cells osteoblasts : osteoblasts Bone forming cells. Derived from mesenchymal stem cells of the bone marrow stroma. These cells deposit bone matrix & are frequently referred as Endosteal osteoblasts or Periosteal osteoblasts. Slide 72: Periosteal osteoblasts are present on the outer surface of bones beneath the periosteum. Endosteal osteoblasts line the vascular canals within bone. They are fully differentiated cells but lack the capacity for migration & proliferation. Slide 73: Thus undifferentiated mesenchymal progenitor cells (osteoprogenitor cells) must migrate to the site & proliferate to become osteoblasts. Friedenstein (1973) divided osteoprogenitor cells into : Determined Inducible osteogenic precursor cells Slide 74: Determined cells are present in the bone marrow, Endosteum & Periosteum. They have an intrinsic capacity to proliferate & differentiate into Osteoblasts. Inducible osteogenic precursor cells, represent mesenchymal cells that may differentiate into bone-forming cells when exposed to stimuli. Slide 75: Osteoblats control mineralization at 3 levels : -in initial phase, by production of matrix vesicle: Calcification. -at a later stage, controls mineralization through release of different enzymes. -by regulating number of ions Slide 76: Osteoblasts can be separated into subpopulations : Those that synthesize bone matrix Those that line trabeculae & endosteal surfaces Those which are called Osteocytes & are buried in their lacunae Those on the surface of bone Functions of osteoblasts : Functions of osteoblasts Well known for synthesizing organic matrix & controlling mineralization. Synthesize & lay down precursors of collagen I, which comprises 90-95% of organic matrix of bone. Also produce Osteocalcin- most abundant non-collagenous protein of bone matrix & Proteoglycans of ground substance along with Osteonectin, Osteopontin. Slide 78: During osteogenesis, secrete growth factors, including Transforming growth factor β, BMP’s, Platelet derived growth factor & Insulin like growth factor. Plays a role in production of paracrine & autocrine factors. Also produce proteases, which are involved in matrix degradation & maturation. osteocytes : osteocytes Most abundant cells. Few osteoblasts gets entrapped within the matrix they secrete, called Osteocytes. Lie in Osteocytic lacunae. Narrow extensions of these lacunae form enclosed channels, Canaliculi, that house osteocytic processes. Slide 82: Through these channels , osteocytes are in contact with other cells. An ideal position to : -sense biochemical & mechanical environments -respond & transduce signals Affect response of other cells to maintain bone integrity & vitality. Have shown to express TGF-β. Slide 83: Considered as nerve cells, maintaining balance between resorption & remodelling. Osteocytic osteolysis. Extracellular matrix : - type I collagen - Osteocalcin - Osteopontin - Osteonectin osteoclasts : osteoclasts Cells for resorption’ cover only 1% of bone surface. Activity controlled by parathyroid hormone. Fused Monocytes Large, multinucleated giant cells (50 nuclei), highly motile with enlarged golgi apparatus Slide 85: Located in Howship’s lacunae. Ruffled border forms adjacent to the area to be resorbed. Is formed by villus like projections & secrete proteolytic enzymes. Consists of folds & invaginations, to allow contact between membrane & surface. Slide 86: At the periphery, the plasma membrane is devoid of cell organelles but enriched in : - Actin - Vinculin - Talin - Fibrillar contractile proteins Called as Clear zone. When activated,attaches to bone matrix by forming a tight ringlike zone of adhesion,called the Sealing zone. Slide 87: Clear zone Slide 88: An electron dense, interfacial matrix layer ( Lamina limitans) is present between sealing zone & calcified tissue surface. Osteopontin facilitates : - osteoclast adhesion - formation of sealing zone Slide 89: Sequence of resorptive events : Attachment of osteoclasts to bone surface. Creation of sealed acidic microenvironment by proton pump, demineralizes bone & expose matrix. Degradation of exposed matrix by Acid Phosphatase & Cathepsin B. Slide 90: Endocytosis at the ruffled border. Translocation of products . Extracelllar release along membrane opposite ruffled border (Transcytosis). Bone lining cells : Bone lining cells Similar to osteocytes Retired osteoblasts Are quiescent & flattened against bone Do not form gap free barrier Maintain communication with osteocytes via gap junctioned processes Slide 93: Maintain receptor for parathyroid hormone & estrogen. Play a role in transferring minerals into & out of bone & in sensing mechanical strain. Bone metabolism : Bone metabolism Primary reservoir of Calcium. Calcium has essential life support function : -maintain pH balance by producing Phosphates & Carbonates. -conduction of nerve & muscle electrical charges. Slide 95: Bone structure & mass are directly affected by body’s metabolic state. Unmet calcium requirement leads to altered structural integrity of bone. In post menopausal women, due to decreased estrogen levels : -bone mass begins to dwindle -interconnections between bone trabeculae are lost Slide 96: Declining Estrogen levels increase risk of implant failure. Metabolic-hormonal interactions help to maintain coupled cycle of resorption & bone apposition. About 0.7% of human skeleton is resorbed & replaced by healthy bone everyday. Normal turnover occurs in every 142 days. Modeling & remodelling : Modeling & remodelling Bone modeling : sculpting & shaping of bones after they have grown in length. Can be controlled by mechanical factors eg orthodontic movement. Slide 98: Occurs during wound healing Associated with growth & formation of bones in childhood & adolescence. Is continuous & occurs at periosteum & endosteum. : Bone remodeling : sequential, coupled, cyclical process that usually maintains the status quo & does not change size & shape of bone. Involves 2 processes: resorption & apposition. These are coupled & characterized by BMU. Occurs throughout life. Slide 101: Osteoclasts move through bone, the leading edge of resorption: Cutting cone Migration of mononucleated cells into osteoblasts,produce a coating: Cement or Reversal line On top of reversal line, osteoblasts lay down new bone matrix. Entire area of osteon where active formation occurs: Filling cone Slide 104: Current concept : osteoclastic precursors get activated differentiate into osteoclasts, begin resorption. Followed by bone formation phase through a Coupling mechanism. Factors regulating bone formation : Factors regulating bone formation Bone formation involves : -production of new organic matrix -mineralization of matrix Controlled by : -systemic hormones -local factors Slide 107: Systemic hormones regulate growth factor activity by : -regulating factor synthesis & release from cells -factor is released in latent form -regulating receptor binding -regulating production of a binding protein Growth factors : Growth factors Platelet derived growth factor Heparin binding growth factor Insulin-like growth factor Transforming growth factor beta Bone morphogenic proteins Features of growth factors : Features of growth factors Factors regulating bone formation have common features : - are polypeptides -exert their activity by binding to specific receptors on cell surface -natural products of cells -multifunctional Platelet-derived growth factor : Platelet-derived growth factor Is a cationic heparin binding polypeptide. Molecular weight : 30,000 d. Consists of a disulfide linked dimer : PDGF-A & PDGF-B 3 isoforms exist : PDGF-AA, PDGF-AB, PDGF-BB Slide 111: Functions of PDGF : -DNA synthesis & cell replication in osteoblasts -increases bone-collagen synthesis -increases rate of bone-matrix apposition Has been reported to increase resorption & collagen degradation. Heparin-binding growth factors : Heparin-binding growth factors Members of a family of a 7 related heparin-binding proteins. Forms are : aFGF &bFGF. Bone matrix is a rich source of FGFs. Enhance collagen & non-collagen protein synthesis. Insulin-like growth factors : Insulin-like growth factors Are nonglycosylated polypeptides. Molecular weight : 7500 d. 2 forms : - IGF-1 or Somatomedin C - IGF-2 or Multiplication-stimulating activity Slide 114: IGF-1 : principle growth regulator in bone & cartilage. Liver is major source of circulating IGF-1 & is the target tissue for production. IGF-1 & IGF-2 most abundant & synthesized by fibroblasts & osteoblasts. Slide 115: Production increased by : - Growth hormone - Estradiol - local factors like PGE2 Production inhibited by : Cortisol Act as either autocrine or paracrine regulators of bone formation. Slide 116: Functions : -increase pre-osteoblastic cell replication -stimulatory effect on osteoblastic collagen synthesis & bone apposition -decrease the degradation of collagen -maintainence of bone mass Transforming growth factor βeta : Transforming growth factor βeta Polypeptides with molecular weight of 25,000 d. Synthesized in cartilage cells. TGF-α plays a role in causing hypercalcemia. Slide 118: TGF-β1, TGF-β2, TGF-β3 present at intramembranous & endochondral ossification sites. TGF-β1 : Proliferating & prehypertrophic cell zone TGF-β2 : hypertrophic & calcifying cartilage. TGF-β3 : proliferating & hypertrophic cell zone Slide 119: TGF-β is synthesized by osteoblasts in latent form. Functions : -preosteoblastic cell replication -osteoblastic collagen synthesis -bone matrix apposition Bone morphogenic proteins : Bone morphogenic proteins Belongs to a family of proteins consisting of 15 members. Has osteoinductive activity. Also stimulate collagen production by mature osteoblasts. Induces chondrocyte differentiation & matrix mineralization. Factors regulating bone resorption : Factors regulating bone resorption Cytokines have been suggested as the cause of increased localized osteolytic bone destruction. These are : - Interleukin 1 - Interleukin 6 - Tumour necrosis factor & Lymphotoxin - Gamma interferon - Colony stimulating factors - Prostaglandins & Arachidonic acid metabolites Interleukin 1 : Interleukin 1 Powerful & potent bone resorbing cytokine. Effects by 2 mechanism : -stimulation of production & release of PGE2; stimulates resorption -direct action of IL-1 on osteoblast Interleukin 6 : Interleukin 6 In some experimental models, it seems to have no effect on bone resorption. In others, do stimulate resorption. Stimulate formation of cells with an osteoclastic phenotype. Tumour necrosis factor & lymphotoxin : Tumour necrosis factor & lymphotoxin Similar effects on bone cells. Both multifunctional cytokines. Share same receptor. Stimulate osteoclastic bone resorption. Also affect cells with osteoblast phenotypes & inhibits function. Gamma interferon : Gamma interferon Multifunctional cytokine. Effects similar to TNF or IL-1. Effect on bone resorption is opposite to that of TNF or IL-1. More effective in inhibiting IL-1β or TNF induced resorption. Colony-stimulating factors : Colony-stimulating factors Have the ability to stimulate differentiation of osteoclast precursors into mature osteoclasts. Possible that CSF’s mediate their effects on osteoclast formation indirectly. Prostaglandins & a. acid metabolites : Prostaglandins & a. acid metabolites Arachidonic acid metabolites are produced by immune, marrow & bone cells. Prostaglandins of E series are first described & best tested stimulators of osteoclastic resorption. Are slow acting but powerful mediators Slide 128: Affect both active mature osteoclasts & differentiated osteoclast precursors. Local effect & mediate the effects of EGF & TGF-β. PGE produced by osteoblasts, affects formation also. Regulation of bone by systemic hormones : Regulation of bone by systemic hormones Hormones responsible are : -Parathyroid hormone -1,25-Dhydroxyvitamin D3 -Calcitonin -Estrogen PARATHYROID HORMONE : PARATHYROID HORMONE Acts on both bone-resorbing & bone-forming cells. Effect depends upon administration. If continuous administration, increases resorption & suppresses bone formation. If intermittent, stimulates bone formation- anabolic effect of PTH. Slide 131: PTH responsiveness is used as criteria for characterizing cells of osteoblast lineage. Osteoblasts response to PTH : -Increase in adenylate cyclase activity -changes in proliferation -alkaline phosphatse activity -production of type I collagen osteoclastogenesis : osteoclastogenesis 1,25-dihydroxyvitamin d3 : 1,25-dihydroxyvitamin d3 Catabolic effect on bone. Promotes absorption of calcium & phosphorus from gut. Has a slow onset of action : -increases osteoclast no. & activity -increase in ruffled border size & clear zone volume calcitonin : calcitonin Inhibits osteoclastic bone resorption (Friedman et al 89). Effect mediated through cAMP. Inhibits formation of new osteoclasts & causes separation of osteoclasts into mononuclear cells. ESCAPE phenomenon. estrogen : estrogen Inhibits the increase in bone resorption associated with menopause. Inhibits prostaglandin secretion by bone cells, can affect remodeling as well. Enhances the expression of TGF-β & IGF-1 in cells with osteoblast phenotype. Bone healing : Bone healing Repair : healing of a tissue that differs in morphology or function from the original tissue. Regeneration : healing that leads to complete restoration of morphology & function. Slide 137: Healing includes 4 phases : -blood clotting -wound cleansing -tissue formation -tissue modeling & remodeling Conditions for regenration : Conditions for regenration The supply of bone-forming cells or cells with the capacity to differentiate into bone-forming cells. Presence of osteoinductive stimuli to initiate differentiation of mesenchymal cells into osteoblasts. Presence of osteoconductive environment forming a scaffold upon which invading tissue can proliferate. Factors interfering healing : Factors interfering healing Failure of vessels to proliferate into the wound. Improper stabilization of coagulam & granulation tissue defect. Ingrowth of non-osseous or fibrous tissues with a high proliferative activity.\ Bacterial contamination conclusion : conclusion Given bone tissues ability to adapt its mass & morphology to functional demands, its ability to repair itself without a scar & its capability to rapidly mobilize mineral stores on metabolic demand, makes it the ultimate smart material & a dynamic eg of form follows function in biological systems. Recent studies have identified key genes, core binding factor a1 & osteoprotegerin which have become important targets for developing pharmacological & clinical strategies to regulate the rate of bone formation & resorption for maintainance of healthy periodontium. refrences : refrences Periodontology 2000 Ten Cate’s : Oral Histology,6 edition Wilsons : Physiology of bone, chap 7 Jan Lindhe : Bone as a Tissue, chap 4 Grants’s : Textbook of Anatomy Orban’s Oral Histology & Embryology Arun Garg : Bone biology, harvesting, grafting for dental implants THANK U : THANK U You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.
Bone biology drpriyam Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 1393 Category: Education License: All Rights Reserved Like it (7) Dislike it (0) Added: October 19, 2009 This Presentation is Public Favorites: 2 Presentation Description No description available. Comments Posting comment... By: redrose1 (14 month(s) ago) thanx Saving..... Post Reply Close Saving..... Edit Comment Close By: kaipei (15 month(s) ago) Good and Comprehensive contents about bone biology Saving..... Post Reply Close Saving..... Edit Comment Close By: f_sharaby (19 month(s) ago) good lecture please, send a copy thx Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Bone biology : Bone biology By Priyam Mishra First year PG Dept of Periodontics & Implantology Sree Balaji dental college Chennai Introduction : Introduction Rigid organs They function - move, support & protect Made mostly of collagen, bone is a living & growing, mineralized tissue. Serves 2 primary functions: -structural support -calcium metabolism Classification : Classification A: - According to position -axial : bones forming the axis of skeleton Eg – skull, ribs, sternum & vertebrae. -appendicular: bones forming the skeleton of limbs. Slide 4: B:- According to size & shape -Long bones : present in upper & lower limbs. Eg – humerus, radius, ulna etc. -Short long bones : eg – Metacarpals, Metatarsals & Phalanges -Short bones : Eg – Carpal & Tarsal bones Slide 5: Short long bones Long bones Slide 6: Short bones Slide 7: -Flat bones : Protect vital structures & provide extensive areas for muscular attachment. Eg – Scapula, Sternum, Ribs, Parietal & Frontal bones -Irregular bones : eg – vertebrae & some skull bones. Slide 8: -Pneumatic bones : flat or irregular bones possessing a hollow space within the body which contains air. Eg – Ethmoid & Maxilla. -Sesamoid bones : do not possess periosteum & Haversian systems. Ossify after birth. Eg- Pisiform & Patella (largest in Femoris Quadriceps). : C:- According to gross structure -Compact bone or lamellar bone : Outer cortical part of long bones. Hard & homogenous in appearance. Gives protection, support & resist stress. -Trabecular bone : Accounts for 20% of total bone mass. Eg – flat, short & irregular bones. Slide 10: -Diploic bone : Has inner & outer tables of Compact bone with an intervening porous layer. Eg – most of Cranial bones. -Accessory bones: Failure of normal ossification centre to fuse to main part of bone or appearance of an extra ossification centre may both simulate a fracture on x-ray. Eg- a persistent Metopic suture. Slide 11: D:- According to development -Membranous bones : develop in membrane. -Cartilaginous (endochondral) bones : develop in cartilage. functions : functions Protection shape Blood production Growth factor storage Endocrine organ Detoxification Sound transduction Fat storage Mineral storage Movement Acid-base balance Composition : Composition Bone is composed of 2/3 of inorganic matter & 1/3 of organic matter. Inorganic part : Calcium & Phosphates – 95% Magnesium Trace elements – Ni, Fe, Cd, F, Zn & Molybdenum. Slide 14: Organic part : Collagen – 88-90% (type I) Non collagenous substances – 10-11% Glycoproteins – 6-9% Proteoglycans – 0.8% Sialoproteins – 0.35% Lipids – 0.4% Non-collagenous proteins : Non-collagenous proteins Osteocalcin : inhibits mineralization : recruits bone cell precursors Osteonectin or SPARC : facilitates type I collagen mineralization : suppresses rate of hydroxyapatite crystal growth : modulates cell attachment & deattachment Slide 16: Osteopontin : cell binding activity :osteoclast anchoring activity :mineral binding activity Bone sialoprotein : cell binding activity Bone proteoglycan II (Decorin) : binds to collagen fibre : regulate fibre growth : binds or presents growth factors in matrix Slide 17: Thrombospondin : cell attachment : binds & organizes matrix Matrix gla-protein : prevents growth plate mineralization Latent TGF-β1binding protein 1 : storage of latent TGF-β1 BLOOD SUPPLY : BLOOD SUPPLY Circulus articularis vasculosis : supply the epiphysis & metaphysis. Nutrient artery anastomoses with numerous metaphyseal & epiphyseal arteries. Periosteal vessels supply outer third of cortex. Medullary vessels, inner two-thirds of cortex. Lymphatics & nerve supply : Lymphatics & nerve supply Found accompanying vascular plexus. Nerves are distributed freely within periosteum & accompany blood vessels. Found in interior of bone in perivascular spaces of Haversian canals. osteogenesis : osteogenesis Development of bone : Development of bone Development involves : -Endochondral ossification -Intramembranous ossification -Sutural ossification Slide 22: The process by which bone tissue replaces membranous fibrous tisssue : Intramembranous ossification. Eg, flat bones of Calvarium. Diaphysis increase in width throughout postnatal growth. Intrmembranous ossification : Intrmembranous ossification Area of mesenchyme prior to mesenchymal condensation Slide 24: Cells are closely packed to form mesenchymal condensation Slide 25: Collagen fibres are laid down between mesenchymal cells Slide 26: osteoblasts Bundle of collagen fibres Slide 27: osteiod Slide 28: Osteiod converted to lamella of bone Endochondral ossification : Endochondral ossification Involves replacement of cartilaginous model by bone. Occur in long bones, Femur & Humerus. Also called Intercartilaginous ossification. Slide 31: Sequence of ossification includes : Primary ossification centre : -takes place in centre of future bone shaft. -cartilage cells hypertrophy & cartilage matrix becomes calcified. Bone collar : -cells of perichondrium begins to form bone. -collar holds together shaft, weakened by cartilage disintegration. Slide 33: Periosteal buds : -connective tissue buds or sprouts containing mesenchymal cells & vessels. -grow from periosteum to reach primary ossification centre. -osteoblasts produce osteoid. Slide 34: Secondary ossification centres : -about time of birth, appears in each end of long bone. -cartilage between centres , called Epiphyseal plate. -Epiphyseal line : union point of ossification centres. Slide 36: Five zones of cartilage are associated with endochondral ossification : Zone of reserve cartilage- large zone & typical hyaline cartilage Zone of cell proliferation- small cells arranged in columns, indicates mitotic activity Slide 37: Zone of cell & lacunar maturation & hypertrophy enlargement- chondrocytes increase in size & resorb lacunar wall Zone of calcification- small zone, chondrocytes die here Zone of cartilage removal & bone deposition Cartilage zones : Cartilage zones Sutural ossification : Sutural ossification Play important role in growing face & skull. Fibrous joints between bones. Function : to permit the skull & face to accommodate growing organs such as eyes & brain. Slide 40: At the suture, the outer layer of periosteum splits into :outermost leaf :innermost leaf The outermost leaf unites with the outermost leaf of other side. The inner leaf, called Capsule along with cambium runs down the suture. Same osteogenic potential as periosteum. Structure of bone : Structure of bone Can be described as : -Macroscopic structure -Microscopic structure -Molecular structure Macroscopic structure : Macroscopic structure Based on porosity, there can be : -dense cortical tissue -spongy cancellous tissue CORTICAL BONE : CORTICAL BONE Cortical or compact bone 85% of total bone in body. Found in shafts of long bones & forms a shell around vertebral bodies & other spongy bones. Haversian system Compact bone : Compact bone Trabecular bone : Trabecular bone 15% of total bone Found in cuboidal & flat bones & in the ends of long bones. Bone matrix in the form of plates called Trabeculae. Medullary cavities : has red & yellow marrow Slide 49: Mature or adult bones consist of lamellae or microscopic layers. Three distinct types are : Circumferential Concentric Interstitial Slide 50: Circumferential lamellae : enclose the entire adult bone, forming its outer perimeter. Concentric lamellae : make up the bulk of compact bone & form the basic metabolic unit of bone, the Osteon. Interstitial lamellae : interspersed between adjacent concentric lamellae & fill the spaces between them. osteon : osteon Basic metabolic unit of bone Is a cylinder of bone, parallel to the long axis of the bone. In the centre has haversian canal which is lined by a single layer of bone cells; each canal houses a capillary. Adjacent canals are connected by Volkmann canals, creating a rich vascular network. periosteum : periosteum Except for the articular surfaces, the outer surface of bone is covered with Periosteum. Site of considerable - metabolic - cellular - biomechanical activities Slide 55: Composed two layers of specialized connective tissue. The outer fibrous layer - dense collagenous fibres & fibroblasts. The inner cellular or Cambium layer, is in direct contact with bone, contains functional osteoblasts. Slide 56: Has various functions: -acts as a medium of attachment -nutrition -presence of Osteoprogenitor cells -fibrous layer or Limiting layer endosteum : endosteum Medullary cavities & spaces are covered by Endosteum. It’s a thin delicate membrane consisting of a single layer of osteoblasts. Its architecturally similar to Cambium layer of Periosteum. Microstructure : Microstructure Four types of bone : - woven - composite - lamellar - bundle Woven bone : Woven bone Plays a principle role in healing Forms very quickly, approximately 30 to 60 mm/day. Disorganized Soft Slide 60: Can be more mineralized than Lamellar bone, helps to compensate for its lack of organization. Composite bone : Composite bone Refers to the transitional state between Phase I bone & Lamellar (phase II) bone. A Woven bone lattice filled with Lamellar bone can be seen. Lamellar bone : Lamellar bone Most abundant mature , load bearing bone in the body. Extremely strong Forms slowly, approximately 0.6 to 1mm/day Well organized collagen protein & mineralized structure with multiple layers. Slide 63: Haversian system Haversian canal Interstitial system Bundle bone : Bundle bone Principle bone found around ligaments & joints. Consists of striated interconnections with ligaments. Molecular structure : Molecular structure Bone is made up of : - type I collagen -water -hydroxyapatite material -proteoglycans -non collagenous proteins Collagen - tensile strength & flexibility -place for the nucleation of bone mineral crystal -rigidity & strength Slide 66: Organic portion : - occupies 35% of matrix - formed by osteocollagenous fibres. These are joined by a cement like substance that consists of Glucosaminoglycan (protein-polysaccharide). Slide 67: Inorganic component : - comprises 65% of bone weight - localized only in the interfibrinous cement. Minerals : mainly hydroxyapatite crystals. Also contains Carbonate, Fluoride, Proteins & Peptides. Other components such as BMP, regulate how bone is laid down & maintained Slide 68: Bone matrix has sequential layers, varying in thickness from 300 to 700 microns. Result of rhythmic & uniform matrix deposition. Bone cells : Bone cells Cells of bone are : Osteoblasts Osteocytes Osteoclasts Bone lining cells osteoblasts : osteoblasts Bone forming cells. Derived from mesenchymal stem cells of the bone marrow stroma. These cells deposit bone matrix & are frequently referred as Endosteal osteoblasts or Periosteal osteoblasts. Slide 72: Periosteal osteoblasts are present on the outer surface of bones beneath the periosteum. Endosteal osteoblasts line the vascular canals within bone. They are fully differentiated cells but lack the capacity for migration & proliferation. Slide 73: Thus undifferentiated mesenchymal progenitor cells (osteoprogenitor cells) must migrate to the site & proliferate to become osteoblasts. Friedenstein (1973) divided osteoprogenitor cells into : Determined Inducible osteogenic precursor cells Slide 74: Determined cells are present in the bone marrow, Endosteum & Periosteum. They have an intrinsic capacity to proliferate & differentiate into Osteoblasts. Inducible osteogenic precursor cells, represent mesenchymal cells that may differentiate into bone-forming cells when exposed to stimuli. Slide 75: Osteoblats control mineralization at 3 levels : -in initial phase, by production of matrix vesicle: Calcification. -at a later stage, controls mineralization through release of different enzymes. -by regulating number of ions Slide 76: Osteoblasts can be separated into subpopulations : Those that synthesize bone matrix Those that line trabeculae & endosteal surfaces Those which are called Osteocytes & are buried in their lacunae Those on the surface of bone Functions of osteoblasts : Functions of osteoblasts Well known for synthesizing organic matrix & controlling mineralization. Synthesize & lay down precursors of collagen I, which comprises 90-95% of organic matrix of bone. Also produce Osteocalcin- most abundant non-collagenous protein of bone matrix & Proteoglycans of ground substance along with Osteonectin, Osteopontin. Slide 78: During osteogenesis, secrete growth factors, including Transforming growth factor β, BMP’s, Platelet derived growth factor & Insulin like growth factor. Plays a role in production of paracrine & autocrine factors. Also produce proteases, which are involved in matrix degradation & maturation. osteocytes : osteocytes Most abundant cells. Few osteoblasts gets entrapped within the matrix they secrete, called Osteocytes. Lie in Osteocytic lacunae. Narrow extensions of these lacunae form enclosed channels, Canaliculi, that house osteocytic processes. Slide 82: Through these channels , osteocytes are in contact with other cells. An ideal position to : -sense biochemical & mechanical environments -respond & transduce signals Affect response of other cells to maintain bone integrity & vitality. Have shown to express TGF-β. Slide 83: Considered as nerve cells, maintaining balance between resorption & remodelling. Osteocytic osteolysis. Extracellular matrix : - type I collagen - Osteocalcin - Osteopontin - Osteonectin osteoclasts : osteoclasts Cells for resorption’ cover only 1% of bone surface. Activity controlled by parathyroid hormone. Fused Monocytes Large, multinucleated giant cells (50 nuclei), highly motile with enlarged golgi apparatus Slide 85: Located in Howship’s lacunae. Ruffled border forms adjacent to the area to be resorbed. Is formed by villus like projections & secrete proteolytic enzymes. Consists of folds & invaginations, to allow contact between membrane & surface. Slide 86: At the periphery, the plasma membrane is devoid of cell organelles but enriched in : - Actin - Vinculin - Talin - Fibrillar contractile proteins Called as Clear zone. When activated,attaches to bone matrix by forming a tight ringlike zone of adhesion,called the Sealing zone. Slide 87: Clear zone Slide 88: An electron dense, interfacial matrix layer ( Lamina limitans) is present between sealing zone & calcified tissue surface. Osteopontin facilitates : - osteoclast adhesion - formation of sealing zone Slide 89: Sequence of resorptive events : Attachment of osteoclasts to bone surface. Creation of sealed acidic microenvironment by proton pump, demineralizes bone & expose matrix. Degradation of exposed matrix by Acid Phosphatase & Cathepsin B. Slide 90: Endocytosis at the ruffled border. Translocation of products . Extracelllar release along membrane opposite ruffled border (Transcytosis). Bone lining cells : Bone lining cells Similar to osteocytes Retired osteoblasts Are quiescent & flattened against bone Do not form gap free barrier Maintain communication with osteocytes via gap junctioned processes Slide 93: Maintain receptor for parathyroid hormone & estrogen. Play a role in transferring minerals into & out of bone & in sensing mechanical strain. Bone metabolism : Bone metabolism Primary reservoir of Calcium. Calcium has essential life support function : -maintain pH balance by producing Phosphates & Carbonates. -conduction of nerve & muscle electrical charges. Slide 95: Bone structure & mass are directly affected by body’s metabolic state. Unmet calcium requirement leads to altered structural integrity of bone. In post menopausal women, due to decreased estrogen levels : -bone mass begins to dwindle -interconnections between bone trabeculae are lost Slide 96: Declining Estrogen levels increase risk of implant failure. Metabolic-hormonal interactions help to maintain coupled cycle of resorption & bone apposition. About 0.7% of human skeleton is resorbed & replaced by healthy bone everyday. Normal turnover occurs in every 142 days. Modeling & remodelling : Modeling & remodelling Bone modeling : sculpting & shaping of bones after they have grown in length. Can be controlled by mechanical factors eg orthodontic movement. Slide 98: Occurs during wound healing Associated with growth & formation of bones in childhood & adolescence. Is continuous & occurs at periosteum & endosteum. : Bone remodeling : sequential, coupled, cyclical process that usually maintains the status quo & does not change size & shape of bone. Involves 2 processes: resorption & apposition. These are coupled & characterized by BMU. Occurs throughout life. Slide 101: Osteoclasts move through bone, the leading edge of resorption: Cutting cone Migration of mononucleated cells into osteoblasts,produce a coating: Cement or Reversal line On top of reversal line, osteoblasts lay down new bone matrix. Entire area of osteon where active formation occurs: Filling cone Slide 104: Current concept : osteoclastic precursors get activated differentiate into osteoclasts, begin resorption. Followed by bone formation phase through a Coupling mechanism. Factors regulating bone formation : Factors regulating bone formation Bone formation involves : -production of new organic matrix -mineralization of matrix Controlled by : -systemic hormones -local factors Slide 107: Systemic hormones regulate growth factor activity by : -regulating factor synthesis & release from cells -factor is released in latent form -regulating receptor binding -regulating production of a binding protein Growth factors : Growth factors Platelet derived growth factor Heparin binding growth factor Insulin-like growth factor Transforming growth factor beta Bone morphogenic proteins Features of growth factors : Features of growth factors Factors regulating bone formation have common features : - are polypeptides -exert their activity by binding to specific receptors on cell surface -natural products of cells -multifunctional Platelet-derived growth factor : Platelet-derived growth factor Is a cationic heparin binding polypeptide. Molecular weight : 30,000 d. Consists of a disulfide linked dimer : PDGF-A & PDGF-B 3 isoforms exist : PDGF-AA, PDGF-AB, PDGF-BB Slide 111: Functions of PDGF : -DNA synthesis & cell replication in osteoblasts -increases bone-collagen synthesis -increases rate of bone-matrix apposition Has been reported to increase resorption & collagen degradation. Heparin-binding growth factors : Heparin-binding growth factors Members of a family of a 7 related heparin-binding proteins. Forms are : aFGF &bFGF. Bone matrix is a rich source of FGFs. Enhance collagen & non-collagen protein synthesis. Insulin-like growth factors : Insulin-like growth factors Are nonglycosylated polypeptides. Molecular weight : 7500 d. 2 forms : - IGF-1 or Somatomedin C - IGF-2 or Multiplication-stimulating activity Slide 114: IGF-1 : principle growth regulator in bone & cartilage. Liver is major source of circulating IGF-1 & is the target tissue for production. IGF-1 & IGF-2 most abundant & synthesized by fibroblasts & osteoblasts. Slide 115: Production increased by : - Growth hormone - Estradiol - local factors like PGE2 Production inhibited by : Cortisol Act as either autocrine or paracrine regulators of bone formation. Slide 116: Functions : -increase pre-osteoblastic cell replication -stimulatory effect on osteoblastic collagen synthesis & bone apposition -decrease the degradation of collagen -maintainence of bone mass Transforming growth factor βeta : Transforming growth factor βeta Polypeptides with molecular weight of 25,000 d. Synthesized in cartilage cells. TGF-α plays a role in causing hypercalcemia. Slide 118: TGF-β1, TGF-β2, TGF-β3 present at intramembranous & endochondral ossification sites. TGF-β1 : Proliferating & prehypertrophic cell zone TGF-β2 : hypertrophic & calcifying cartilage. TGF-β3 : proliferating & hypertrophic cell zone Slide 119: TGF-β is synthesized by osteoblasts in latent form. Functions : -preosteoblastic cell replication -osteoblastic collagen synthesis -bone matrix apposition Bone morphogenic proteins : Bone morphogenic proteins Belongs to a family of proteins consisting of 15 members. Has osteoinductive activity. Also stimulate collagen production by mature osteoblasts. Induces chondrocyte differentiation & matrix mineralization. Factors regulating bone resorption : Factors regulating bone resorption Cytokines have been suggested as the cause of increased localized osteolytic bone destruction. These are : - Interleukin 1 - Interleukin 6 - Tumour necrosis factor & Lymphotoxin - Gamma interferon - Colony stimulating factors - Prostaglandins & Arachidonic acid metabolites Interleukin 1 : Interleukin 1 Powerful & potent bone resorbing cytokine. Effects by 2 mechanism : -stimulation of production & release of PGE2; stimulates resorption -direct action of IL-1 on osteoblast Interleukin 6 : Interleukin 6 In some experimental models, it seems to have no effect on bone resorption. In others, do stimulate resorption. Stimulate formation of cells with an osteoclastic phenotype. Tumour necrosis factor & lymphotoxin : Tumour necrosis factor & lymphotoxin Similar effects on bone cells. Both multifunctional cytokines. Share same receptor. Stimulate osteoclastic bone resorption. Also affect cells with osteoblast phenotypes & inhibits function. Gamma interferon : Gamma interferon Multifunctional cytokine. Effects similar to TNF or IL-1. Effect on bone resorption is opposite to that of TNF or IL-1. More effective in inhibiting IL-1β or TNF induced resorption. Colony-stimulating factors : Colony-stimulating factors Have the ability to stimulate differentiation of osteoclast precursors into mature osteoclasts. Possible that CSF’s mediate their effects on osteoclast formation indirectly. Prostaglandins & a. acid metabolites : Prostaglandins & a. acid metabolites Arachidonic acid metabolites are produced by immune, marrow & bone cells. Prostaglandins of E series are first described & best tested stimulators of osteoclastic resorption. Are slow acting but powerful mediators Slide 128: Affect both active mature osteoclasts & differentiated osteoclast precursors. Local effect & mediate the effects of EGF & TGF-β. PGE produced by osteoblasts, affects formation also. Regulation of bone by systemic hormones : Regulation of bone by systemic hormones Hormones responsible are : -Parathyroid hormone -1,25-Dhydroxyvitamin D3 -Calcitonin -Estrogen PARATHYROID HORMONE : PARATHYROID HORMONE Acts on both bone-resorbing & bone-forming cells. Effect depends upon administration. If continuous administration, increases resorption & suppresses bone formation. If intermittent, stimulates bone formation- anabolic effect of PTH. Slide 131: PTH responsiveness is used as criteria for characterizing cells of osteoblast lineage. Osteoblasts response to PTH : -Increase in adenylate cyclase activity -changes in proliferation -alkaline phosphatse activity -production of type I collagen osteoclastogenesis : osteoclastogenesis 1,25-dihydroxyvitamin d3 : 1,25-dihydroxyvitamin d3 Catabolic effect on bone. Promotes absorption of calcium & phosphorus from gut. Has a slow onset of action : -increases osteoclast no. & activity -increase in ruffled border size & clear zone volume calcitonin : calcitonin Inhibits osteoclastic bone resorption (Friedman et al 89). Effect mediated through cAMP. Inhibits formation of new osteoclasts & causes separation of osteoclasts into mononuclear cells. ESCAPE phenomenon. estrogen : estrogen Inhibits the increase in bone resorption associated with menopause. Inhibits prostaglandin secretion by bone cells, can affect remodeling as well. Enhances the expression of TGF-β & IGF-1 in cells with osteoblast phenotype. Bone healing : Bone healing Repair : healing of a tissue that differs in morphology or function from the original tissue. Regeneration : healing that leads to complete restoration of morphology & function. Slide 137: Healing includes 4 phases : -blood clotting -wound cleansing -tissue formation -tissue modeling & remodeling Conditions for regenration : Conditions for regenration The supply of bone-forming cells or cells with the capacity to differentiate into bone-forming cells. Presence of osteoinductive stimuli to initiate differentiation of mesenchymal cells into osteoblasts. Presence of osteoconductive environment forming a scaffold upon which invading tissue can proliferate. Factors interfering healing : Factors interfering healing Failure of vessels to proliferate into the wound. Improper stabilization of coagulam & granulation tissue defect. Ingrowth of non-osseous or fibrous tissues with a high proliferative activity.\ Bacterial contamination conclusion : conclusion Given bone tissues ability to adapt its mass & morphology to functional demands, its ability to repair itself without a scar & its capability to rapidly mobilize mineral stores on metabolic demand, makes it the ultimate smart material & a dynamic eg of form follows function in biological systems. Recent studies have identified key genes, core binding factor a1 & osteoprotegerin which have become important targets for developing pharmacological & clinical strategies to regulate the rate of bone formation & resorption for maintainance of healthy periodontium. refrences : refrences Periodontology 2000 Ten Cate’s : Oral Histology,6 edition Wilsons : Physiology of bone, chap 7 Jan Lindhe : Bone as a Tissue, chap 4 Grants’s : Textbook of Anatomy Orban’s Oral Histology & Embryology Arun Garg : Bone biology, harvesting, grafting for dental implants THANK U : THANK U