FIGURE 1.

Pathogenesis of osteoarthritis. Within the OA-affected joints, macrophages play a critical role by secreting pro-inflammatory cytokines and chemokines such as IL-8, MCP-1, CXCL12, CCL22, and MIP-1α in response to various stimuli including hypoxia and low molecular HA. These inflammatory mediators contribute to the activation of chondrocytes. Activated chondrocytes express elevated levels of matrix-degrading proteases, particularly MMP1, 3, 9, and 13, via the NF-κB and MAPK signaling pathways, induced by pro-inflammatory factors like PGE-2, NO, and COX-2. This upregulation of proteases leads to the degradation of the extracellular matrix, a hallmark of OA progression. The figure underscores the importance of the NF-κB and MAPK pathways in the catabolic processes of cartilage degradation, highlighting potential targets for therapeutic intervention to mitigate the progression of OA.