Limited roles of Piezo mechanosensing channels in articular cartilage development and osteoarthritis progression

Abstract

To investigate the role of Piezo1 and Piezo2 in surgically induced osteoarthritis (OA) in mice. Male conditional knockout (cKO) mice missing Piezo1 and Piezo2 in the joint using Gdf5-Cre transgenic mice were induced with post-traumatic OAby destabilization of the medial meniscus (DMM) of the right knee joint at 12 weeks of age. The severity of OA was histologically assessed at 24 weeks of age. OA-associated pain was evaluated by static weight bearing analysis. Additionally, articular chondrocytes isolated from cKO mice were exposed to fluid flow shear stress (FFSS) to evaluate the expression of OA-associated genes. Mice with conditional deletion of Piezo1 and Piezo2 showed normal joint development with no overt histological changes in the knee joint at 12 weeks and 24 weeks. DMM surgery induced moderate to severe OA in both control and cKO mice (median OARSI score: control, 4.67; cKO, 4.23, P=0.3082), although a few cKO mice showed milder OA. Pain assessment by static weight-bearing analysis suggested Piezo ablation in the joint has no beneficial effects on pain. FFSS increased the expression of OA-related genes both in control and cKO mice to similar extents. Piezo1 and Piezo2 are not essential for normal joint development. Genetic ablation of Piezo channels did not confer evident protective effects on OA progression in mice. In vitro data suggests that different mechanotransducers other than Piezo channels mediate FFSS in mechanical stress-induced gene expression.