Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China.
Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China.
Exp Cell Res. 2018 Jan 1;362(1):51-62. doi: 10.1016/j.yexcr.2017.11.001. Epub 2017 Nov 1.
Ca signaling is essential for bone metabolism. Fluid shear stress (FSS), which can induce a rapid release of calcium from endoplasmic reticulum (ER) to produce calcium transients, plays a significant role in osteoblast proliferation and differentiation. However, it is still unclear of how calcium transients induced by FSS activating a number of downstream signals which subsequently regulate cell functions. In this study, we performed a group of Ca transients models, which were induced by FSS to investigate the effects of different magnitudes of Ca transients in osteoblast proliferation. Further, we performed a global proteomic profile of MC3T3-E1 cells in different Ca transients models stimulated by FSS. GO enrichment and KEGG pathway analysis revealed that the TCA cycle was activated in the proliferating process. The activation of TCA needed mitochondrial Ca uptake which were influenced by the amplitude of Ca transients induced by FSS. Our work elucidate that osteoblast proliferation induced by FSS was related to the magnitude of calcium transients, which further activated energetic metabolism signaling pathway. This work revealed further understanding the mechanism of osteoblast proliferation induced by mechanic loading and help us to design new methods for osteoporosis therapy.
钙信号对于骨骼代谢至关重要。流体切应力（FSS）能够引发内质网（ER）中钙的快速释放，产生钙瞬变，在成骨细胞增殖和分化中发挥重要作用。然而，目前尚不清楚 FSS 诱导的钙瞬变如何激活大量下游信号，进而调节细胞功能。在这项研究中，我们构建了一组钙瞬变模型，通过 FSS 诱导钙瞬变来研究不同幅度的钙瞬变对成骨细胞增殖的影响。此外，我们还对 FSS 刺激下不同钙瞬变模型中的 MC3T3-E1 细胞进行了全蛋白质组学分析。GO 富集和 KEGG 通路分析表明，TCA 循环在增殖过程中被激活。TCA 的激活需要线粒体摄取钙，而这又受到 FSS 诱导的钙瞬变幅度的影响。我们的工作表明，FSS 诱导的成骨细胞增殖与钙瞬变的幅度有关，进一步激活了能量代谢信号通路。这项工作进一步揭示了机械加载诱导成骨细胞增殖的机制，有助于我们设计新的骨质疏松症治疗方法。
