GPM6B Regulates Osteoblast Function and Induction of Mineralization by Controlling Cytoskeleton and Matrix Vesicle Release
GPM6B Regulates Osteoblast Function and Induction of Mineralization by Controlling Cytoskeleton and Matrix Vesicle Release
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DOI：
10.1002/jbmr.435
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发表时间：
2011-09-01
影响因子：
6.2
通讯作者：
van Leeuwen, Johannes P. T. M.
中科院分区：
文献类型：
--
作者：
Drabek, Ksenija;van de Peppel, Jeroen;van Leeuwen, Johannes P. T. M.
神经细胞膜糖蛋白基因(GPM6B)编码一种膜糖蛋白，属于蛋白脂蛋白家族。我们发现GPM6B是一个在成骨细胞分化过程中强烈上调的基因。为了研究GPM6B在骨形成过程中的作用，我们在人骨髓间充质干细胞(HMSCs)成骨分化过程中沉默了GPM6B的表达。GPM6B沉默hMSCs导致碱性磷酸酶(ALP)活性降低，细胞外基质(ECM)矿化减少。GPM6B缺失的成骨hMSCs的微阵列表达分析显示，细胞骨架组织和生物发生相关的基因发生了显著变化。免疫细胞化学结果证实了GPM6B沉默时肌动蛋白细丝的分布以及局部粘连的形状和大小的变化。此外，我们还证实了碱性磷酸酶阳性基质小泡(MVS)的产生和释放减少。总之，我们确定GPM6B是一种新的成骨细胞功能和骨形成的调节因子。这一发现表明，细胞骨架组织对MV的产生和随后的矿化具有重要意义。(C)2011年美国骨与矿物研究学会。
Neuronal membrane glycoprotein gene (GPM6B) encodes a membrane glycoprotein that belongs to the proteolipid protein family. We identified GPM6B as a gene that is strongly upregulated during osteoblast differentiation. To investigate the role of GPM6B in the process of bone formation, we silenced GPM6B expression during osteogenic differentiation of human mesenchymal stem cells (hMSCs). GPM6B silencing in hMSCs resulted in reduced alkaline phosphate (ALP) activity along with reduced mineralization of extracellular matrix (ECM). Microarray expression analysis of GPM6B-depleted osteogenic hMSCs revealed significant changes in genes involved in cytoskeleton organization and biogenesis. Immunocytochemistry results confirm changes in the distribution of actin filaments, as well as the shape and size of focal adhesions on GPM6B silencing. Moreover, we demonstrated that production and release of ALP-positive matrix vesicles (MVs) were reduced. In conclusion, we identified GPM6B as a novel regulator of osteoblast function and bone formation. This finding demonstrates the significance of cytoskeleton organization for MV production and subsequent mineralization. (C) 2011 American Society for Bone and Mineral Research.