The renin-angiotensin system in the synovium promotes periarticular osteopenia in a rat model of collagen-induced arthritis.

Periarticular osteopenia is the most specific hallmark of rheumatoid arthritis (RA). The renin–angiotensin system (RAS) in the synovium has been found to participate in the pathogenic process of RA. This study examined whether and how RAS regulates periarticular osteopenia in RA. The synovial tissues from patients with RA and osteoarthritis (OA) were prepared. Female Sprague-Dawley rats were treated with either saline, bovine type II collagen (CII) to induce arthritis (CIA), or CII combined with perindopril, an inhibitor of angiotensin-converting enzyme (ACE). Expressions of RAS components, including AT1R, AT2R and ACE, in human and rat synovial tissues were detected. Bone mass of rat joints was examined. Levels of RANKL, OPG and DKK-1 in rat synovium and expressions of TRAF6 and β-catenin in rat bone were examined. The results showed that AT1R, AT2R and ACE in human and rat synovium were up-regulated, but the increased ACE in rat synovial tissues was abrogated by perindopril. While CIA rats displayed increased bone resorption and decreased bone formation, perindopril treatment almost completely abrogated the RAS-mediated osteopenia, indicating that inhibition of ACE reduced the joint damages in rats. The expressions of RANKL and DKK-1 increased in CIA rats as compared with those in the control; TRAF6 was up-regulated and β-catenin was down-regulated in the bone tissues of CIA rats. The changes were then reversed by the use of perindopril. Our findings demonstrate that RAS in the synovium promotes periarticular osteopenia by increasing bone resorption and decreasing bone formation through modulating the RANKL/RANK/TRAF6 and Wnt/β-catenin pathways.