The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion

- The cation channel TRPV2 is expressed in synovial fibroblasts.
- TRPV2 agonists, including the new LER13, reduce the invasiveness of synovial fibroblasts.
- TRPV2 agonists reduce disease severity in two well-established models of rheumatoid arthritis.
- TRPV2 agonists reduced joint damage, synovial inflammation, and synovial angiogenesis in models of rheumatoid arthritis.
- This is the first time that TRPV2 agonists are used in vivo, and there was no evidence of toxicity.

Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1β-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and synovial blood vessel numbers suggesting anti-angiogenic activity. In this first in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in arthritis. These new compounds have the potential to become new therapies for RA and other diseases associated with inflammation, invasion, and angiogenesis.