Stimulation of calcium influx and suppression of autophagy play important roles in the pathogenesis of osteoarthritis (OA). In this study, we used a novel inhibitor of TRPV5 cation channels - oxoglaucine to attenuate progression of deterioration and pathological changes in OA patient-derived chondrocytes and OA animal model, by activating autophagy.
Inhibition by oxoglaucine of calcium influx was assessed in cells.. Analyses were also carried out to investigate the effect of oxoglaucine on OA by detection of anti-inflammatory response, TRPV5/CAMK-II/calmodulin pathway, autophagy, and cartilage protection both in vitro and in vivo. demonstrated by macroscopic evaluation and histological findings.
Oxoglaucine suppressed expression of proinflammatory and apoptosis-related proteins, including TNF-α, IL-6, IL-1β, MMP-13, CASP-3, and BAX, and prevented matrix degradation in OA chondrocytes. It also successfully blocked Ca
Oxoglaucine protects against cartilage damage by blocking the TRPV5/CAMK-II/calmodulin pathway to inhibit Ca