A740003 Can Reverse Chondrocyte Apoptosis and Prevent Extracellular Matrix Degradation by NF-KB Pathway in Facet Joint Osteoarthritis

Facet joint osteoarthritis (FJOA) is one of the common causes of low back pain, but the molecular mechanism is still unclear. Previous studies have found that P2X7 receptor has been proved to play an important role in skeletal and joint diseases. The purpose of this study was to explore the role of A740003, selective P2X7R antagonist, in the development of FJOA. Our study found that A740003 can inhibit the expression of P2X7R in OA chondrocytes. It can lead to anti-inflammatory and anti-apoptotic effects in primary chondrocytes by IL-1β/BzATP. Our results imply that decreased P2X7R can reverse chondrocyte apoptosis and prevent extracellular matrix degradation by NF-KB pathway. Moreover, in our present work, we found that A740003 inhibit the abrrently activation of NF-KB pathway by preventing the activated P65 translocation to nucleus. Our results indicate that P2X7R is a therapeutic target for the treatment of FJOA, and that A740003 could be a therapeutic candidate for this clinical application.