Calcium signaling of primary chondrocytes and ATDC5 chondrogenic cells under osmotic stress and mechanical stimulation.
Calcium signaling of primary chondrocytes and ATDC5 chondrogenic cells under osmotic stress and mechanical stimulation.
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DOI：
10.1016/j.jbiomech.2022.111388
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发表时间：
2022-12
影响因子：
2.4
通讯作者：
Lucas Lu, X
中科院分区：
文献类型：
--
作者：
Li, Wen;Zhou, Yilu;Han, Lin;Wang, Liyun;Lucas Lu, X
钙信号在软骨细胞的机械转导中起着重要作用。Guilak及其同事揭示了TRPV4和Piezo通道在软骨细胞钙信号和代谢中的作用。本研究比较了原代软骨细胞和ATDC5细胞在两种不同刺激条件下的钙反应：渗透应激和强烈机械刺激。细胞外钙源、胞内内质网钙储存和机械敏感离子通道等三条重要的钙信号通路在细胞间的作用也进行了研究和比较。原代软骨细胞在渗透压下表现出比机械刺激下更强烈的钙峰，而ATDC5细胞则表现出相反的趋势。细胞外钙源、胞内内质网储存和PLC/IP3通路在渗透和机械刺激下ATDC5细胞的钙反应中均起重要作用。然而，高水平的切应力可以直接导致原代细胞内ER的释放，而不需要细胞外钙离子的存在或PLC-IP3途径的参与。TRPV4通道对ATDC5细胞的反应是必需的，但对原代软骨细胞不是必需的。相反，机械敏感通道的抑制对ATDC5细胞没有显著影响。因此，原代软骨细胞和ATDC5细胞依赖于不同的钙来源和离子通道来启动细胞内钙信号。综上所述，这些结果有助于我们理解刺激诱导的原代软骨细胞和ATDC5细胞中的钙信号，以及这两种细胞类型之间三种基本途径的不同作用。
Calcium signaling plays an essential role in chondrocyte mechanotransduction. Guilak and colleagues have revealed the roles of TRPV4 and Piezo channels in chondrocyte calcium signaling and metabolism. This study compared the calcium responses of primary chondrocytes and ATDC5 cells induced by two different stimuli: osmotic stress and intense mechanical stimulus. Roles of three essential calcium signaling pathways, including extracellular calcium source, intracellular ER calcium store and mechanical-sensitive ion channels, were also investigated and compared between cells. Primary chondrocytes showed more vigorous calcium peaks under osmotic stress than under mechanical stimuli, while an opposite trend was found for ATDC5 cells. Extracellular calcium source, intracellular ER store, and PLC/IP3 pathway each played significant roles in the calcium responses of ATDC5 cells under both osmotic and mechanical stimuli. However, high level shear stress can directly cause ER release in primary cells without the presence of extracellular Ca2+ or involvement of PLC-IP3 pathway. TRPV4 channel is essential for the responses of ATDC5 cells, but not for primary chondrocytes. In contrast, inhibition of mechano-sensitive channels had no significant effects on the ATDC5 cells. Therefore, primary chondrocytes and ATDC5 cells rely on distinct calcium sources and ion channels to initiate intracellular calcium signaling. Together, these results contribute to our understanding of stimulation-induced calcium signaling in primary chondrocytes and ATDC5 cells, and the different roles of three essential pathways between the two cell types.