title: The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.
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.
authors: Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA.
authors: Teresina
authors: T
authors: Laragione
authors: Laboratory of Medicinal Chemistry, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors: Kai F
authors: KF
authors: Cheng
authors: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA; Graduate Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.
authors: Mark R
authors: MR
authors: Tanner
authors: Laboratory of Medicinal Chemistry, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors: Mingzhu
authors: M
authors: He
authors: Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
authors: Christine
authors: C
authors: Beeton
authors: Laboratory of Medicinal Chemistry, The Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors: Yousef
authors: Y
authors: Al-Abed
authors: Division of Rheumatology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, USA. Electronic address: percio.gulko@mssm.edu.
authors: Pércio S
authors: PS
authors: Gulko
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002185:Cannabidiol / Q000031:analogs & derivatives / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D003094:Collagen / Q000633:toxicity; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D051379:Mice; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects; D050916:TRPV Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013729:Terpenes / Q000633:toxicity; D046509:Tissue Culture Techniques
chemical_list: D015220:Calcium Channels; D002186:Cannabinoids; C000600514:O-1821 compound; D034741:RNA, Small Interfering; D050916:TRPV Cation Channels; C400769:TRPV2 protein, human; D013729:Terpenes; C485717:Trpv2 protein, mouse; C476722:Trpv2 protein, rat; D002185:Cannabidiol; C009042:pristane; D003094:Collagen
keywords: Angiogenesis; Arthritis; Autoimmunity; Ion channels; Pathogenesis; Synovitis