Figure 7

Schematic demonstrating the inflammatory cycle that inhibits chondrogenic differentiation of MSCs in OA and the effect of curcumin. Trauma, inflammation or a combination of both (1) lead to the production and accumulation of high levels of pro-inflammatory cytokines (2) in the joint. These trigger the production of additional pro-inflammatory cytokines which induce genes encoding prostaglandin synthesizing enzymes (that is, COX-2) and matrix degrading enzymes (3) such as MMPs and aggrecanases. These events promote cartilage degradation and stimulate further joint inflammation (4) and a self-perpetuating inflammatory and catabolic cascade develops. As illustrated, cartilage contains chondrocytes and MSC-like progenitors (5). Chemical or biological agents may help create a suitable microenvironment in order for these progenitor cells to undergo chondrogenesis and regenerate new cartilage in OA. In this study we tested the hypothesis that phytochemical modulators of NF-κB can counteract this inflammatory and catabolic cascade and demonstrated that curcumin (6) has the capacity to block the action of pro-inflammatory cytokines in the joint thus disrupting the inflammatory cycle.