A disintegrin and metallproteinase15 knockout decreases migration of fibroblast-like synoviocytes and inflammation in rheumatoid arthritis.

Abstract

The aim of the present study was to determine whether the expression of A disintegrin and metallproteinase15 (ADAM15) affected the inflammatory conditions and cell migration in human fibroblast‑like synoviocytes (FLSs) in a rat model of rheumatoid arthritis (RA). The expression of ADAM15 in FLSs stimulated with lipopolysaccharide (LPS) was confirmed by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The effects of small interfering RNA targeting ADAM15 (siADAM5) on pro‑inflammatory cytokines and chemokines were assessed using an enzyme‑linked immunosorbent assay. The effects of siADAM15 on cell invasion and migration in FLS were also assessed invitro. The therapeutic effects and side effects of ADAM15 in a rat model of collagen‑induced arthritis (CIA) were examined invivo. The present results revealed that ADAM15 expression was significantly elevated at the mRNA and protein level in FLSs stimulated with LPS and that silencing ADAM15 suppressed the expression of pro‑inflammatory cytokines and chemokines, preventing FLS cell migration and invasion via inhibiting vascular endothelial growth factor‑A, matrix metalloproteinase (MMP)1 and MMP‑3 expression. In addition, treatment of CIA rats using siADAM15 significantly reduced the arthritis score and extent of joint damage in the rats. These findings indicated that silencing ADAM15 had anti‑inflammatory effects in FLSs and efficiently inhibited the development of CIA. Therefore, ADAM15 may be a potential target molecule for RA therapies.