STRUCTURE, INJURY & HEALING

1. ARTICULARCARTILAGE STRUCTURE, INJURY & HEALING Nadhaporn Saengpetch Division of Sports Medicine, Department of Orthopaedics, Faculty of Medicine Ramathibodi Hospital, Mahidol University

2. COMPOSITION • Extracellular matrix and sparse cells • No blood vessel, lymphatic vessel and nerve • limit response to any metabolic response • Frictionless

3. CHONDROCTYE • Endoplasmic reticulum and Golgi apparatus (matrix synthesis) • Intracytoplasmic filament, lipid, glycogen, secretary vesicles (maintenance of matrix structure)

4. CHONDROCYTE: DIFFERENT BY LAYERS • Surface layer: elongated and resemble fibroblasts • Transitional layer: round and actively for chemistry • Deeper layer: cells in radial pattern • Tidemark: non-functionalcells

5. COLLAGEN FIBRILS

6. CHONDROCYTE: FUNCTION • NOT participate in water distribution • Maintenance and structural competence • Producing and replacing appropriate macromolecules (degradation, mechanical demand placed on the surface, synthesizing) • Assembling as an highly ordered framework

7. CARTILAGE ZONES

8. EXTRACELLULAR MATRIX (ECM) • 2 components 1. Tissue fluid 2. Framework of structural macromolecule • Interaction -> stiffness and resilience

9. ECM • Water 80% by weight • Gel forming = lubrication system • Large aggregation of Proteoglycans (maintain fluid within the matrix and e’lyte concentration)

10. ECM MOVEMENT Cl- Na+ Cl- Na+ inorganic ion tissue osmolarity

11. STRUCTURAL MACROMOLECULES

12. STRUCTURAL MACROMOLECULES • Collagens • Proteoglycans • Noncollagenous proteins 20-40% wet wt.

13. COLLAGEN • 60% of dry weight of cartilage • Collagen-rich superficial zone • Types: II*, VI, IX, X and XI • Type II, IX and XI form the cross-band fibrils

14. TIGHT MESHWORK Large proteoglycans entrapment Collagen fibrils organization Tensile stiffness & cartilage strength Cohesiveness of tissue

15. TYPE II COLLAGEN • 90-95% of cartilage collagen • The primary component of cross-banded fibrils

16. TYPE VI COLLAGEN • Forms an important part of surrounding chondrocytes • Helps chondrocyte attach to matrix

17. TYPE IX COLLAGEN • Bind covalently to superficial layers of cross-banded fibrils • Project into the matrix to bind with other Type IX Collagenand Proteoglycans Have GAG-> Proteoglycan?

18. TYPE X COLLAGEN TYPE XI COLLAGEN • Found only near cartilage calcified zone and hypertrophic zone of growth plate (start to mineralize) • Cartilage mineralization • Bind covalently to Type II • Mayform part of interior structure of cross-banded fibrils

19. PROTEOGLYCANS • A protein core & Glycosaminoglycans (GAG) chains (unbranched polysaccharide) • GAG: Hyaluronic acid, chondroitin sulfate, glucosamine sulfate, dermatan sulfate

21. AGGRECANS • Mostly fill in the interfibrillar space of matrix • 90% of Pg mass • Noncovalently bind with HA & monomer • Help anchor Pg in the matrix, prevent displacement during deformation, organize and stabilize Pg & collagen

22. DECORINS • One dermatan sulfate chain

23. BIGLYCAN & FIBROMODULIN • Two dermatan sulfate chains • Several dermatan sulfate chains Biglycan Fibromodulin

24. Healing + Degradative enzymes Transforming growth factor β

25. HYALURONIC ACID • Backbone for matrix aggregation • Bind aggrecans non-covalently and link proteins • This aggregation helps anchor Pg within the matrix • Prevent displacement during deformation • Stabilize relationships of Pg and collagen meshwork

26. NONCOLLAGENOUS PROTEINS & GLYCOPROTEINS • Stabilize the matrix framework • Help chondrocytes bind to the macromolecules of matrix • Anchorin CII collagen-binding chondrocytes surface protein (anchor) • Cartilage oligomeric protein (COMP) is in chondrocyte territorial matrix, have capacity to bind to chondrocyte

27. ZONES OF ARTICULAR CARTILAGE

28. SUPERFICIAL ZONE • Thinnest zone • Two sub layers: • sheet of fine fibrils (acellular) • flattened ellipsoid-shape chondrocyte + fibroblast • Collagen is lying parallel to the joint surface (resist compressive force)-> OA • High collagen, low Pg • “cartilage skin”

29. TRANSITIONAL ZONE • Large volume • cells: synthetic organelles (ER, Golgi) spheroidal shape • Lower collagen & water concentration • Higher Pg concentration

30. MIDDLE(RADIAL/DEEP) ZONE • Chondrocytes align in columns perpendicular to the joint surface (resist shear stress) • Largest diameter collagen • Highest Pg • Lowest water • Collagen fibers pass into the tidemark

31. CALCIFIED CARTILAGE ZONE • Thin calcified cartilage • “calcific sepulchers” • Extremely low level of metabolic activity • No nutrients traverse this zone

32. MATRIX REGIONS • Pericellular • Territorial • Interterritorial>>> • Bind cell membranes to matrix macromolecules • Protect deformation force • Transmit mechanical signals to chondrocytes • Provide the mechanical properties of tissue

33. CHONDROCYTE-MATRIX INTERACTIONS • Matrix protects chondrocytes from mechanical damage and maintain shape and phenotype • Matrix : metabolic products/cytokines and growthfactors • Insulin-dependent growth factor I (IGF-I) & Transforming growth factor β (TGF β) +matrix synthesis & cell proliferation

34. CHONDROCYTE-MATRIX INTERACTIONS IGF-I TGF β +

35. BIOMECHANICS Tension Compression Shear • Wide range of static & dynamic mechanical loads • Compressive, tensile & shear forces αcomposition & structure of ECM

36. TENSILE & SHEAR FORCE • These forces are resisted by rope-like collagen fibrils

37. COMPRESSIVE FORCE • Resisted by highly charged GAG such as aggrecan molecules

38. LOADING vs IMMOBILIZATION Induced wide range of metabolic response Decreased in matrix synthesis

39. CARTILAGE REGENERATION Static compression Reversibly inhibit cartilage matrix synthesis Cyclical compressive Stimulate aggrecan core protein & protein synthesis

40. DEGENERATION AND OSTEOARTHRITIS • Osteoarthritis >> degenerative joint disease, degenerative arthritis, hypertrophic arthritis

41. HOW THEY CHANGE?

42. OA: 3 OVERLAPPING PROCESSES • Cartilage matrix damage • Chondrocyte response to tissue damage • Decline of the chondrocyte synthetic response

43. STAGE 1 MATRIX DAMAGE Water Aggrecan & GAG length Permeability & Matrix stiffness Other causes: inflammation, tissue’s metabolic changes that interferes matrix maintenance

44. STAGE 2 CHONDROCYTE RESPONSE • Chondrocytes detect tissue damage Anabolic & mitogenic growth factors chondrocyte proliferation & ECM + Reversible • Spontaneous • Intervention Catabolic enzymes (proteases)

45. STAGE 3 DECLINE CELL SYNTHESIS • Failure to restore the tissue • Progressive loss of cartilage • Down regulation of chondrocyte response to anabolic cytokine

46. JOINT INJURY &POSTTRAUMATIC OA • Ligament reconstruction (ex. ACL-R) can restore mechanical stability but not greatly reduce the risk for OA development because…. The initial traumatic event may have irreversible effects on the joint tissues and residents cells

47. Good Luck