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Connective Tissue and Bone

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Connective Tissue and Bone Connective Tissue and Bone Peter Takizawa [email protected] What we will talk about… • Types and functions of connective tissue • Cells of connective tissue • Composition and structure of bone • Cells that control the shape and integrity of bone • Development of bone Connective tissue serves a variety of functions throughout the body. Resist stress Organize tissues Connective Tissue Immunity Metabolic Bacterium Fat cell Macrophage Connective tissue can generate a range of mechanical strengths. Organ Blood Cartilage Tendon Bone Support Vessels Connective tissue resists tension and compression. Collagen Elastin Glycosamino- glycans Connective tissue can be classified based on the amount and organization of collagen. Dense Regular Dense Irregular Loose Glycoproteins Collagen Collagen Reticular fibers are composed of type III collagen and organize cells in organs. Cells Reticular Fiber Adipose tissue contains adipocytes that store large amounts of lipid and triglycerides. Cytoplasm Lipids Nucleus Brown fat stores lipids and triglycerides and generates heat. Lipid Droplets Nucleus Cells of connective tissue Fibroblasts are prominent in connective tissue and synthesize most of the protein components. Areolar Tissue Collagen Fiber Collagen Fibroblast Mast cells store and release histamine during an immune response Mast Cell Macrophage engulf foreign particles and cellular debris. Macrophage Cartilage Chondrocytes synthesize cartilage which resists compression. Nucleus Matrix Lipid Droplets Chondrocyte Hyaline cartilage contains type II cartilage and glycosaminoglycans. Toluidine Blue H&E Perichondrium Matrix Chondrocytes Fibrocartilage contains a large amount of type I collagen. Collagen Fibers Matrix Chondrocytes Elastic cartilage contains elastic fibers and type II collagen. Elastic Fiber Chondrocyte Bone Bone serves mechanical, metabolic and cellular functions. Ca2+ The major structure components of bone are calcium-phosphate crystals and type I collagen. Collagen Composition of bone Ca2+ cyrstals Fibril Mineralized collagen fibril Bone can be arranged in lamellar or woven forms. Lamellar Woven Architecture of bone Compact bone and trabecular bone are two structures in most bones. Trabecular Bone Epiphysis Endosteal Surface Periosteal Surface Diaphysis Compact Bone Compact bone is organized into circumferential lamellae and Haversian systems. Circumferential bone Haversian system Periosteal Surface Haversian Canal Volkmann’s Canal Volkmann’s Canal Haversian Canal Bone Cells Osteoblasts secrete collagen and catalyze the crystallization of calcium on collagen fibers. Osteoblasts synthesize osteoid that mineralizes into bone. Osteoblast Osteoid Bone Osteoid Bone Osteocytes are osteoblasts that become trapped in bone matrix. Osteoblast Osteocyte Ground section of Haverisan System showing osteocytes and their filopodia Haversian Canal Filopodia Osteocyte Osteocytes communicate via gap junctions on filopodia. Osteocyte Gap junction Bone Filopodia Canalicullus Osteoclasts Osteoclasts secrete acid on bone to dissolve calcium-phosphate crystals. Cl- CO2 H2O CA HCO3- CO2 ADP Pi H+ Cl- ATP H+ H+ Cl- Cl- Osteoclasts secrete cathepsin K onto bone to digest collagen. Transcytosis delivers digested bone matrix components to basal side of osteoclasts. Histological image and electron micrograph showing an osteoclast Osteoclast Bone Bone Dynamics of bone turnover Bone is a dynamic material that undergoes synthesis and resorption. Synthesis Increase length or store Ca2+ Resorption Increase Ca2+ levels Resorption Maintain integrity Synthesis Osteoblasts and osteoclasts reshape bone and replace old bone. Reshape Bone modeling bone Replace Bone remodeling bone Osteoblast Osteoclast Bone modeling Bone modeling shapes bone with osteoblasts and osteoclasts working on different surfaces. Trabecular bone aligns along lines of stress. Periosteal apposition and endocortical resorption increase diameter of bone. Seeman (2008) J Bone Miner Metab 26 1-8 Osteocytes use a primary cilium to detect mechanical stress in bone. Primary cilium Fluid flow Ca2+ Bone remodeling Bone remodeling removes old bone and replaces it with new bone. Compact bone Trabecular bone Remodeling repairs bone with osteoclasts and osteoblasts working on the same surface. Activation/Resorption Formation Reversal Basic multicellular unit consists of osteoclasts, osteoblasts that remodel compact bone. Osteoblast Osteoclast Kerr Atlas of Functional Histology 1st edition Remodeling erodes old Haversian Systems while forming new canals. Resorption Formation Development of osteoclasts Pre-osteoclasts are activated by M-CSF and RANK ligand on the surface of osteoblasts. Preosteoclast Monocyte RANK receptor Osteoclast M-CSF RANK-L Osteoblast Osteoprotegerin is a decoy receptor for RANKL that prevents activation of preosteoclasts. Monocyte Preosteoclast Osteoclast RANK receptor M-CSF OPG Osteoblast Parathyroid hormone stimulates osteoblasts to increases RANKL and decrease OPGs. RANK receptor Ca2+ PTH RANK-L Osteoblast Estrogen has direct and indirect effects on the development and lifespan of osteoclasts. Estrogen Apoptosis Estrogen Osteoblast OPG synthesis Bone development Intramembraneous ossification involves bone formation on mesenchymal tissue. Bone Mesenchyme Osteoblast Osteocyte Endochondrial ossification is bone formation on cartilage. Cartilage Chondrocyte Cartilage Growth Plate Bone Osteoid Bone Marrow The developmental sequence of chondrocytes drives bone formation in growth plates. Resting Chondrocytes Proliferating Chondrocytes Hypertrophic Chondrocytes Calcified Cartilage Take home points... • The properties of connective tissue is determined by the and arrangement type of ECM components and the cellular composition. • Bones contain of compact bone and trabecular bone. • Osteoblasts synthesize bone and osteoclasts dissolve bone. • Osteocytes are mechanical sensors that regulate bone synthesis and absorption. • Bone modeling reshapes bone and bone remodeling replaces old bone. • Increased activity and numbers of osteoclasts leads to osteoporosis..
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