Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Osteoarthritis (OA) is a low-level inflammatory disease in which synovial macrophage M1 polarization exacerbates the progression of synovitis and OA. Notedly, the ROS (reactive oxygen species) level in macrophages is intimately implicated in macrophage M1 polarization. TRPV4 (transient receptor potential channel subfamily V member 4), as an ion channel, plays a pivotal role in oxidative stress and inflammation. In this study, we investigated the role of TRPV4 in OA progression and M1 macrophage polarization. Male adult Sprague–Dawley (SD) rats underwent a medial meniscus radial transection operation to create an OA model in vivo and RAW 264.7 cells were intervened with 100 ng/mL LPS (lipopolysaccharide) to induce M1-polarized macrophages in vitro. We demonstrated that the infiltration of M1 synovial macrophages and the expression of TRPV4 were increased significantly in OA synovium. In addition, intra-articular injection of HC067074 (a specific inhibitor of TRPV4) alleviated the progression of rat OA and significantly decreased synovial macrophage M1 polarization. Further mechanisms suggested that ROS production by M1 macrophages was decreased after TRPV4 inhibition. In addition, NLRP3 (pyrin domain containing protein 3) as a downstream effector of ROS in M1-polarized macrophage, was significantly suppressed following TRPV4 inhibition. In conclusion, this study discovered that inhibition of TRPV4 delays OA progression by inhibiting M1 synovial macrophage polarization through the ROS/NLRP3 pathway.
Funding Information
  • National Natural Science Foundation of China (81941009, 82172481, 32271409, 021414380528, WSW-079, 2021-NCRC-CXJJ-ZH-16)
  • Fundamental Research Funds for the Central Universities (81941009, 82172481, 32271409, 021414380528, WSW-079, 2021-NCRC-CXJJ-ZH-16)
  • Six Talent Peaks Project of Jiangsu Province (81941009, 82172481, 32271409, 021414380528, WSW-079, 2021-NCRC-CXJJ-ZH-16)
  • Innovation Project of National Orthopedics and Sports Medicine Rehabilitation Clinical Medical Research Center (81941009, 82172481, 32271409, 021414380528, WSW-079, 2021-NCRC-CXJJ-ZH-16)

This publication has 59 references indexed in Scilit: