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

Teresina Laragione, Kai F. Cheng, Mark R. Tanner, Mingzhu He, Christine Beeton, Yousef Al-Abed, Pércio S. Gulko

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)183-192
Number of pages10
JournalClinical Immunology
Volume158
Issue number2
DOIs
StatePublished - 1 Jun 2015

Keywords

  • Angiogenesis
  • Arthritis
  • Autoimmunity
  • Ion channels
  • Pathogenesis
  • Synovitis

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