STIM1钙传感器促进含有细胞外囊泡和调节矿化因子的ECM的组装

Yinghua Chen, Rahul Koshy, Anne George
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摘要

骨和牙本质的发育需要磷酸钙矿物的时空沉积。几种蛋白质协同工作,促进这一严格调控的过程。STIM1(基质相互作用分子1)是一种最近被发现在骨和牙釉质矿化中起作用的蛋白质。STIM1是一种定位于内质网膜上的钙传感器,其在维持钙稳态中的生理作用已得到广泛认可。我们之前已经证明,DMP1刺激成骨前细胞和成牙前细胞刺激钙从内部Ca2+储存中释放,这种储存消耗被STIM1感知。储存操作钙进入(SOCE)是内质网储存耗尽后Ca2+内流的主要机制之一。为了证明STIM1在牙本质基质矿化中的作用,我们产生了STIM1过表达或沉默的转基因DPSCs。通过基因表达分析、茜素红染色和场发射扫描电镜(FESEM)观察基质的拓扑结构,对这些细胞的分化潜力进行了表征。结果表明,参与矿化和钙沉积的基因上调与STIM1过表达。FESEM结果表明,STIM1过表达导致细胞外微泡大量释放,促进基质矿化。有趣的是,抑制STIM1导致ECM中微囊泡的释放减少,矿物质沉积减少。STIM-1缺失小鼠牙本质厚度减少,牙槽骨畸形和高度多孔,证实了STIM1在钙化组织形成中的作用。总的来说,STIM1是生物矿化的关键分子,因为STIM1可以影响细胞内Ca2+振荡,从而为上游和下游效应物的激活提供信号,以促进前体细胞分化和基质矿化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
STIM1 a Calcium Sensor Promotes the Assembly of an ECM that Contains Extracellular Vesicles and Factors that Modulate Mineralization
Bone and dentin development requires temporal and spatial deposition of calcium phosphate mineral. Several proteins work in coordination and contribute to this tightly regulated process. STIM1 (Stromal interaction molecule 1) is one such protein that has been recently identified to function in bone and enamel mineralization. STIM1 is a calcium sensor localized on the ER membrane and is well recognized for its physiological role in maintaining calcium homeostasis. We have demonstrated earlier that DMP1 stimulation of preosteoblasts and preodontoblasts stimulate calcium release from internal Ca2+ stores and this store depletion is sensed by STIM1. Store-operated calcium entry (SOCE) is one of the major Ca2+ influx mechanisms following store depletion in the ER. To demonstrate a role for STIM1 in dentin matrix mineralization, we generated transgenic DPSCs in which STIM1 was either overexpressed or silenced. These cells were characterized for their differentiation potential by gene expression analysis, Alizarin Red staining and the topology of the matrix examined by Field Emission Scanning Electron Microscopy (FESEM). Results suggest upregulation of genes involved in mineralization and increased calcium deposition with STIM1 overexpression. FESEM results demonstrate that STIM1 overexpression resulted in release of large amount of extracellular microvesicles and promoted matrix mineralization. Interestingly, knockdown of STIM1 resulted in release of fewer microvesicles and less mineral deposits in the ECM. Reduced dentin thickness, malformed and highly porous alveolar bone of STIM-1 null mice confirmed the role of STIM1 in the formation of calcified tissues. Overall, STIM1 is a crucial molecule in biomineralization as STIM1 can influence intracellular Ca2+ oscillations and thus provide a signal for activation of upstream and downstream effectors to promote precursor cell differentiation and matrix mineralization.
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