1. Basic science of Cartilage and Joints DR C C Okwara Rheumatologist

2. Joint Is where bones meet and articulate with certain degree of motion Axial and peripheral Small and large Intra-articular and extra-articular components Consist of subchondral bone, cartilage, synovium, capsule, intra-articular ligaments. Extra-articular Ligaments, muscles, tendons,

3. Cartilage subtypes Physeal Cartilage – Enchondral bone growth Fibrocartilage – Ligament,tendon, healing Elastic Cartilage –Trachea, Pinna, Lig flavum Fibroelastic –Menisci Articular

4. Articular Cartilage Avascular, Aneural, Alymphatic Mature vs Immature pH 7.4 Load and Friction Unique nutrition

5. Compostion Water Nutrients and Lubrication 65%-80% of cartilage by weight Unequal distribution – 80% @ surface, 65% deep Shifts allow for deformation properties of cartilage Increased to 90% in OA -> Increased permiability, decreased strength, decreased elasticity (stress/strain)

6. Compostion Collagen - Biochem Alpha chains  triple helix  Tropogollagen in quarter staggered arrangement with pores  Microfibrils Glycine, proline, hydroxyproline – measured in urine to assess bone turnover

7. Collagen 20-25% wet weight, 50% dry Cartilage is 90-95% type II Type XI – adhesive between cartilage Type V, VI*, IX Type X – Hypertrophic chondrocytes – Enchondral ossification/callus formation, HO Responsible for tensile strength

8. Compostion Chondrocytes 5% wet weight Produce collagen, proteoglycans, enzymes Mesenchymal stem cells  chondroblasts  chondrocytes Responsible for extracellular matrix, responsive to various cytokines. Immunopriviledged

9. Layers of articular cartilage Superficial 10-20% - tangential, shear, dense, low metab Middle 40-60% - random, compression Deep 30% - columnar, compression, thick collagen Tidemark – shear. Deep zone crosses tidemark Calcified – anchor to subchond bone

10. Synovium Mediates nutrient exchange between blood and joint fluid Type A (phagocytotic) and Type B (fibrotic, broth providing) cells. Fluid: ultrafiltrate of plasma, hyaluronic acid, lubricin, enzymes, prostaglandins, growth factors. No RBC’s, clotting factors, hgb

11. Growth Factors PDGF - Healing, OA? TGF-B – Proteoglycan synthesis. Inhib. Collagen II and enzymatic degredation, Stimulates TIMP FGF – Chondrocyte DNA synthesis IGF-I – DNA synthesis and, immature cartilage in growth plate. CDGF

12. Mechanical properties biphasic cFr – 0.002-0.04 Coeeficient decreased efflux of fluid from cartilage, elastic deformation, synovial fluid Tensile strength 5% of bone, stiffness 0.1% of bone. Lubrication: Elastohydrodynamic, hydrodynamic, weeping, boundry, boosted, mixed

13. “Healing” Due to avascularity, any lesion superficial to tidemark doesn’t heal Deep to tidemark, fibrocartilage (type I collagen) Immobilization decreases proteoglycan/collagen in 4 weeks, returns in 8 weeks Instability (ACL tears) has some decrease but will increase Prot/coll ratio @ 3 months. Marked decrease in hyaluronin

14. Degradation MMP vs TIMP homeostasis Primarily degradation of proteoglycans Unknown genetetic triggers to this imbalance Basic science has categorized MMP’s and specific cleavage sites. Cartilage oligiomeric matrix protein turnover markers

15. Aging Decreased Water Hypocellular, larger chondrocytes Decreased proteoglycans, c-4-s, increased keratin Less elastic, stiffer (increased young’s modulus), decreased solubility, IL-1 cascade

16. Frontiers in cartilage repair Drilling, abrasion, microfx ACT Growth Factor Augmentation Gene therapy Tissue Engineering

17. MicroFx and the like Based on principle that deep lesions heal. Fibrocartilage replacement considerably inferior to articular cartilage, primarily type I collagen, with relatively rapid wear and decreased hyluronan

18. Gene Therapy Transfer of DNA into chondrocytes (viral/non-viral) Hypothesis of in/ex vivo repair. In-vitro studies of TGF-B, IGF-I into chondrocytes showed increased Collagen II,ECM BMP-7 in rabbit mesenchymal stem cells inplanted into osteochondral defects showed markd improvement when compared c placebo. Doxycycline inducer!

19. OITE q 1) What is the predominant cartilage type in osteoarthritic cartilage: 1 I 2 II 3 IV 4 X 5 XI

20. OITE 2) What defect in collagen synthesis is caused by lack of vitamin C 1) Impaired hydroxylation of proline 2) Failure of cleavage of procollagen 3) Defective binding sites for hydroxyproline 4) Failure to incorporate glycine into the helix 5) Dimished production of procollagen through the RER

21. OITE Collagen orientation in the deep layer of normal articular cartilage is aligned? 1) randomly 2) Parallel to the surface not crossing the tidemark 3) Parallel to the surface, crossing the tidemark 4) Perpendicular to the surface not crossing the tidemark 5) Perpendicular to the surface crossing the tidemark

22. OITE What component of cartilage is primarily responsible for retaining fluid in the matrix: 1) Chondrocytes 2) Proteoglycans 3) collagen 4) Noncollagenous proteins 5) Calcium

23. Thank You