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Majid Negari

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Open access Aug 2026

The role of the immune system in the progression of osteoarthritis

Osteoarthritis (OA) is traditionally viewed as a mechanical wear-and-tear disease. While mechanical loading remains a fundamental factor in joint degeneration, it does not fully explain why post-traumatic osteoarthritis (PTOA) progresses so aggressively. We propose a novel biological hypothesis suggesting that a secondary, parallel immunomediated mechanism coexists alongside this mechanical pathway. Articular cartilage normally acts similarly to immune-privileged sites, sequestering internal auto-antigens. However, joint injury breaches this barrier, exposing hidden cartilage proteins to the systemic immune system. This exposure triggers an autoimmune reaction driven by synovial macrophages and T-cells, creating a self-amplifying vicious cycle of immune recruitment and tissue destruction. This parallel cascade prevents joint healing and accelerates degeneration. To validate this model, we outline a pragmatic approach using ELISA to track phase-specific cytokines and animal models to observe progression after immunomodulation. Integrating this immunomediated continuum with classical mechanical theories shifts the therapeutic paradigm of PTOA toward targeted immunomodulatory interventions, offering a dual pathway to halt disease progression.

Majid Negari · 0 citations