Altered spontaneous calcium signaling of in situ chondrocytes in human osteoarthritic cartilage

Intracellular calcium ([Ca2+](i)) signaling is an essential universal secondary messenger in articular chondrocytes. However, little is known about its spatiotemporal features in the context of osteoarthritis (OA). Herein, by examining the cartilage samples collected from patients undergoing knee arthroscopic surgery, we investigated the spatiotemporal features of spontaneous [Ca2+](i) signaling in in situ chondrocytes at different OA stages. Our data showed zonal dependent spontaneous [Ca2+](i) signaling in healthy cartilage samples under 4 mM calcium environment. This signal was significantly attenuated in healthy cartilage samples but increased in early-degenerated cartilage when cultured in 0 mM calcium environment. No significant difference was found in [Ca2+] i intensity oscillation in chondrocytes located in middle zones among ICRS 1-3 samples under both 4 and 0 mM calcium environments. However, the correlation was found in deep zone chondrocytes incubated in 4 mM calcium environment. In addition, increased protein abundance of Ca(v)3.3 T-type voltage dependent calcium channel and Nfatc2 activity were observed in early-degenerated cartilage samples. The present study exhibited OA severity dependent spatiotemporal features of spontaneous [Ca2+](i) oscillations of in situ chondrocytes, which might reflect the zonal specific role of chondrocytes during OA progression and provide new insight in articular cartilage degradation during OA progression.