Cell Biology of the Musculoskeletal System.ppt
- 1. Cell Biology of the Musculoskeletal System by Panji Sananta
- 2. Cell cycle 1. G1 (presynthetic) 2. S (DNA synthesis) 3. G2 (premitotic) 4. M (mitotic ) 5. G0 (physiologic or resting)
- 3. Cell Cycle 1. Continuosly dividing ( labile ) cell 2. Quiescent ( stable) cell 3. Nondividing (permanent) cell
- 4. Cell Cycle Regulation 1. Cascade of protein phosporylation pathways. - Cyclins - Cyclins-dependent kinases
- 5. Cell Cycle Regulation 2. Set of checkpoints - cell cycle arrest - Promoting inhibitory pathways - Inhibiting activating pathways - Loss of check point: 1.genomic instability 2.evolution into cancer
- 7. Cell Signaling *Autocrine signalling cell respond to the signalling they themselves secrete *Paracrine signalling cell produces molecules affect only a target cell in close proximity *Endocrine signalling hormones synthesized by endocrine organs act on distant target cell
- 8. Cell Surface Receptor 1. Receptors with intrinsic kinase activity 2. Receptor without intrinsic kinase activity 3. G Protein- Linked Receptors
- 9. Signal Transduction System  Process by which extracellular signals are detected & converted into intracellular signals -> specific cellular response  Signal transduction pathways: 1. PI3 kinase pathway 2. MAP kinase pathway 3. IP3 pathway 4. cAMP pathway 5. JAK/STAT pathway
- 11. Apoptosis  Programmed cell death  Apoptosis vs nekrosis  Morphologic features: -cell shrinkage -chromatin condensation -formation cytoplasmic blebs & apoptotic body -phagocytosis apoptotic cells or body
- 12. Apoptosis Events
- 13. Extracellular Matrix  Macromolecul assembles into a network in the space surrounding cell.  Critically influences cell functions  Three groups of ECM: 1. Fibrous structural proteins (e.g. collagens & elastin) 2. Adhesive glycoprotein (e.g. fibronectin & laminin) and integrins 3. Proteoglycans & hyaluronan
- 16. Growth Factors  Local protein  Secreted by many cell  Bind to specific receptor  Modulate cell proliferation and differentiation
- 17. Growth Factors
- 18. TGF -β  In articular chondrocytes stimulates proteoglycans synthesis  In bone stimulates osteoblast proliferation & matrix synthesis  Active during bone resorption-> regulate osteoblast & osteoclast interaction
- 19. Role of TGF-β in Tissue Fibrosis
- 20. BMPs  Member of the TGF-β superfamily  BMP-1 ->metalloprotease for collagen types I,II,III  BMP-2 & BMP-7 ->bone regeneration  BMP-6 & BMP-7 -> cartilage maturation
- 21. IGFs  IGF-1 (somatomedin C ) -> proliferation of chondrocytes and proteoglycan synthesis  IGF-2-> proliferation and matrix synthesis by osteoblast
- 22. FGFs  Family of 11 growth factors, FGF-1 & 2 most abundant  Found in cartilage matrix and bone-> proliferation of both cell type  Angiogenic -> stimulating growth of vasculature
- 23. Cytokines  Soluble peptide signaling molecules  More than 100 molecules identified  Produce by many cell: -lymphocytes -> lymphokines -monocytes -> monokines - Proinflammatory cytokines (IL-1, IL-6, TNF-α)-> inflammatory arthritis & bone resorption
- 27. TERIMAKASIH