Calcium is essential to various physiological and pathophysiological cellular processes. Calcium-sensing receptor (CasR), a seven-transmembrane-spanning protein that responds to changes in extracellular Ca²⁺, partly modulates calcium homeostasis, thereby influencing bone metabolism. In this study, we aimed to elucidate the role of CasR in Cd-induced calcium homeostasis disruption and OB apoptosis, and the underlying mechanisms. Cd treatment dramatically increased the protein expression of CasR and elevated the intracellular calcium concentration. Meanwhile, OBs apoptosis rate and caspase-dependent apoptosis protein levels, including cleaved caspase 3, cleaved caspase 9 and the ratio of Bax/Bcl-2 were increased. However, downregulation of CasR by CasR siRNA effectively suppressed the effects of Cd on theses phenomena. At the same time, we illustrated that CasR siRNA pretreatment blocked Cd-inhibited the phosphorylation of PKC and decreased Cd-induced the phosphorylation of PI3K/AKT.

Our results suggested that CasR-mediated PKC and PI3K/AKT signaling pathways involve in calcium oscillation and apoptosis in OB caused by Cd maybe responsible for the bone homeostasis.

钙对于各种生理和病理生理细胞过程至关重要。钙敏感受体（CasR），一种跨膜的七蛋白，可响应细胞外Ca ^2+的变化，部分调节钙稳态，从而影响骨代谢。在这项研究中，我们旨在阐明CasR在Cd诱导的钙稳态破坏和OB凋亡中的作用，以及潜在的机制。镉处理显着增加了CasR的蛋白质表达并提高了细胞内钙的浓度。同时，OB的凋亡率和胱天蛋白酶依赖性凋亡蛋白水平，包括裂解的胱天蛋白酶3，裂解的胱天蛋白酶9和Bax / Bcl-2的比率增加。然而，CasR siRNA对CasR的下调可有效抑制Cd对这些现象的影响。同时，我们说明了CasR siRNA预处理可阻断Cd抑制PKC的磷酸化，并降低Cd诱导的PI3K / AKT的磷酸化。

我们的研究结果表明，CasR介导的PKC和PI3K / AKT信号通路与Cd引起的OB的钙振荡和细胞凋亡有关，可能与骨稳态有关。