musculosceletal

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

6. Cell Cycle Regulation

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

10. Signal Transduction System


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

14. Cell Matrix Interaction

15. Integrin and osteoclast

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

24. Cytokines and Inflammatory
Arthritis

25. Cytokines and Inflammatory
Arthritis

26. Cytokines and Inflammatory
Arthritis

27. TERIMAKASIH