ADAM8 influences the activity of synovial macrophages and fibroblast-like synoviocytes in osteoarthritis

ADAM8's Role in FLS in Osteoarthritis

Abstract

Osteoarthritis (OA) is the most widely diagnosed form of disabling joint disease, and the polarization of macrophages has been demonstrated to influence OA pathogenesis. The knockdown of ADAM8 (a disintegrin and metalloprotease 8) can suppress OA phenotypes, prompting the present study exploring the potential ability of ADAM8 to regulate fibroblast-like synoviocyte (FLS) phenotypes through its effects on the polarization macrophages, ultimately impacting OA progression. Analyses of protein and mRNA expression were conducted through Western immunoblotting and qPCR, the levels of inflammatory factors were assessed by ELISA. While CCK-8 and lactage dehydrogenase release assays were used to quantify cell proliferation and viability. The migratory and invasive activity of FLS cells was also assessed through wound healing and Transwell approaches. The results revealed that M1 macrophages were found to express high levels of ADAM8, thereby promoting inflammatory cytokine production. Knocking down ADAM8 was sufficient to suppress M1 macrophage polarization, thereby indirectly suppressing FLS proliferative, migratory, and invasive activity.These findings suggest thatADAM8 is a key mediator of OA-related inflammation through its ability to promote pro-inflammatory factor expression within M1 macrophages. ADAM8 was also determined to shape FLS phenotypes through the modulation of the polarization of these macrophages, ultimately influencing the progression of OA.