Involvement of Transient Receptor Potential Vanilloid Channel 2 in the Induction of Lubricin and Suppression of Ectopic Endochondral Ossification in Mouse Articular Cartilage

Hideki Nakamoto, Yuki Katanosaka, Ryota Chijimatsu, Daisuke Mori, Fengjun Xuan, Fumiko Yano, Yasunori Omata, Yuji Maenohara, Yasutaka Murahashi, Kohei Kawaguchi, Ryota Yamagami, Hiroshi Inui, Shuji Taketomi, Yuki Taniguchi, Motoi Kanagawa, Keiji Naruse, Sakae Tanaka, Taku Saito

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objective: Transient receptor potential vanilloid channel 2 (TRPV2) is a Ca2+-permeable channel and plays a role in mediating intracellular Ca2+ current via mechanical stimuli. This study was undertaken to examine the expression and role of TRPV2 in adult articular cartilage and the development of osteoarthritis (OA). Methods: We examined TRPV2 expression in mouse and human articular cartilage. We analyzed the development of OA in Col2a1-CreERt2;Trpv2fl/fl mice and Trpv2fl/fl littermates in the resection of the medial meniscus and medial collateral ligament model (n = 5 each), the destabilization of the medial meniscus model (n = 5 each), and the aging mouse model (n = 8–9 each). We examined marker protein expression in these joints, Ca2+ influx by mechanical stimuli, and downstream pathways in vitro. Results: TRPV2 was expressed in mouse and human articular cartilage and ectopic ossification lesions. In all mouse models of OA examined, Col2a1-CreERt2;Trpv2fl/fl mice were observed to have enhanced degradation of articular cartilage accompanied by decreased expression of lubricin/Prg 4, and marked formation of periarticular ectopic ossification. Mechanical stress–induced Ca2+ influx was decreased by Trpv2 knockout (KO). Prg4 induction by fluid-flow shear stress was diminished in Trpv2-KO mouse chondrocytes, and this was mediated by the Ca2+/calmodulin-dependent protein kinase kinase-cyclic AMP response element binding protein axis. Hypertrophic differentiation was enhanced in Trpv2-KO mouse chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor in activated T cells 1 induced by fluid-flow shear stress or TRP agonist treatment was reversed by Trpv2 knockout. Conclusion: Our findings demonstrate regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification.

Original languageEnglish
Pages (from-to)1441-1450
Number of pages10
JournalArthritis and Rheumatology
Volume73
Issue number8
DOIs
Publication statusPublished - Aug 2021

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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