Inhibition of P2Y11R ameliorated TNF-α-induced degradation of extracellular matrix in human chondrocytic SW1353 cells.

Osteoarthritis is a major global health burden. Joint destruction resulting from excessive degradation of type II collagen and aggrecan in the articular extracellular matrix by metalloproteinases and aggrecanases, respectively, is a major pathological hallmark of osteoarthritis. However, the exact mechanisms remain poorly understood. Currently, there are few non-invasive therapies capable of slowing or halting the progression of the disease. In the present study, we investigated the involvement of the P2Y purinergic protein and its receptor P2Y11R in TNF-α-mediated degradation of the extracellular matrix in SW1353 cell line chondrocytes using the novel P2Y11R antagonist NF157. To our knowledge, this is the first study to explore the effects of NF157 in OA. Our results indicate that P2Y11R may indeed play a role in TNF-α-induced degradation of extracellular matrix in OA as treatment with NF157 significantly reduced expression of metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5, and ameliorated degradation of type II collagen and aggrecan in SW1353 chondrocytes in a dose-dependent manner. Furthermore, we show that treatment with NF157 significantly reduced nuclear translocation of p65 and subsequent activation of nuclear factor κB (NF-κB).