Left Side: Joint Comparison
- Normal Joint: Healthy synovium, cartilage, and subchondral bone.
- OA Joint: Shows presence of osteophyte, damaged cartilage, and affected subchondral bone.
Central Box: Inflammatory Environment
Proinflammatory Mediators (Pink Box)
- Cytokines: IL-1, TNF, IL-6, IL-8
- MMPs, ADAMTS: Matrix-degrading enzymes
- Bioactive Lipids: PGE2, LTB4 (promote inflammation and pain)
- Neuropeptides, NO (Nitric Oxide): Contribute to pain and inflammation
- Adipokines: Visfatin/NAMPT, etc. – link with metabolic OA
Anti-inflammatory Mediators (Green Box)
- Cytokines: IL-4, IL-13, IL-1Ra
- TIMPs: Inhibit MMPs
Cartilage and Bone Changes
- Cartilage releases degradation products → drive inflammation.
- BMPs (Bone Morphogenetic Proteins): Involved in bone remodeling.
- Subchondral bone changes contribute to structural alterations.
Right Side: Synovium and Immune Response
Synovial Changes
- Patchy synovitis: Hypertrophy and hyperplasia of the synovium
- Synovial fibroblasts: Active in cytokine release and matrix degradation
Immune Cell Involvement
- Macrophages: Release inflammatory mediators (e.g. IL-12)
- T cells (CD4+) and B cells: Drive chronic inflammation
- CXCL13: Attracts B cells
- IL-12: Activates T cells
- VCAM-1, E-Selectin: Promote immune cell adhesion/migration
- VEGF, EGF: Lead to neovascularization (abnormal blood vessel formation in the synovium)
Key Implications for OA Pathogenesis:
- 1. Synovitis (inflammation of the synovium) plays a central role in perpetuating OA.
- 2. Proinflammatory cytokines and MMPs drive cartilage destruction.
- 3. Immune cell infiltration maintains the inflammatory cycle.
- 4. Subchondral bone and neovascularization contribute to structural and symptomatic progression.