Chondrocytes play a critical role in cartilage remodeling by mediating the biosynthesis, organization, and modification of extracellular matrix (ECM) [1]. Previous studies showed that chondrocytes are highly sensitive to the surrounding mechanical and osmotic environments [2]. However, how these signals are perceived and transduced by chondrocytes remains unclear. One of the earliest responses of chondrocytes to stimuli is a transient oscillation in intracellular Ca2+ concentration ([Ca2+]i) [3]. The major objective of this study was to investigate and compare the Ca2+ signaling of chondrocytes, including both primary cells and chondrogenic cell line, under mechanical stimulus [4] and osmotic stress. The roles of seven essential pathways in Ca2+ signaling were further examined using pharmacological inhibitors.

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