Figure 2.

Feedback loop of serine proteases (HtrA1) to cell receptors (DDR2) and the matrix metalloproteinas-13 (MMP13) degradative pathway in osteoarthritis progression. A mechanical force on the articular cartilage activates HtrA1, which in turn degrades pericellular matrix (PCM) molecules, thus leading to exposure of the chondrocyte’s surface receptors to type II collagen fibrils in the extracellular matrix (ECM). Then, binding of type II collagen fibrils to DDR2 upregulates MMP13, thus leading to degradation of collagen.