TRPV2 is involved in induction of lubricin and suppression of ectopic endochondral ossification in articular joints.

Objective Transient receptor potential vanilloid 2 (TRPV2) is a Ca2+ permeable channel and plays a role in mediating intracellular Ca2+ current via mechanical stimuli. This study aimed to examine the expression and role of TRPV2 in adult articular cartilage and development of osteoarthritis (OA). Methods We examined TRPV2 expression in mouse and human articular cartilage. We analyzed development of OA in Col2a1-CreERT2 ;Trpv2fl/fl 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 model (n = 8-9). 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 models, Col2a1-CreERT2 ;Trpv2fl/fl mice showed enhanced degradation of articular cartilage accompanied by decreased expression of lubricin/Prg4, and marked formation of periarticular ectopic ossification. Mechanical stress-induced Ca2+ influx was decreased by Trpv2 knockout. Prg4 induction by fluid flow shear stress was diminished in Trpv2 knockout chondrocytes, and this was mediated by the Ca2+ /calmodulin-dependent protein kinase kinase-cyclic adenosine monophosphate response element binding protein axis. Hypertrophic differentiation was enhanced in Trpv2 knockout chondrocytes. Increased activity of calcineurin and nuclear translocation of nuclear factor of activated T cells 1 by fluid flow shear stress or TRP agonist treatment were cancelled by Trpv2 knockout. Conclusion This study shows regulation of articular cartilage by TRPV2 through Prg4 induction and suppression of ectopic ossification.