miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression
miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression
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miR-764-5p通过抑制CHIP/STUB1表达促进成骨细胞分化
DOI：
10.1002/jbmr.1597
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发表时间：
2012-07-01
影响因子：
6.2
通讯作者：
Chang, Zhijie
中科院分区：
文献类型：
--
作者：
Guo, Junwei;Ren, Fangli;Chang, Zhijie
定向前体细胞向成骨细胞谱系的分化受到包括Runx 2和BMP 2在内的几种因子的严格调节。我们以前报道过Hsc 70相互作用蛋白/STIP 1同源蛋白C端和含U盒蛋白1（CHIP/STUB 1）通过促进Runx 2蛋白降解负调控成骨细胞分化。然而，在成骨细胞分化过程中，CHIP是如何调节的仍然未知。在本研究中，我们发现miR-764- 5 p在颅骨和成骨祖细胞的成骨分化过程中表达上调，同时CHIP蛋白表达下调。我们观察到miR-764- 5 p的强制表达或抑制通过靶向3 '-UTR区域影响其翻译来降低或增加CHIP蛋白水平。miR-764- 5 p的干扰导致成骨祖细胞分化命运的改变，并且miR-764- 5 p的作用被CHIP的过表达逆转，而CHIP的耗尽削弱了miR-764- 5 p的作用。我们的数据表明，miR-764- 5 p通过抑制CHIP蛋白的翻译，积极调节成骨祖细胞的成骨分化。(c)2012年美国骨与矿物质研究学会。
Differentiation of committed precursor cells into the osteoblast lineage is tightly regulated by several factors, including Runx2 and BMP2. We previously reported that C terminus of Hsc70-interacting protein/STIP1 homology and U-Box containing protein 1 (CHIP/STUB1) negatively regulated osteoblast differentiation through promoting Runx2 protein degradation. However, how CHIP is regulated during osteoblast differentiation remains unknown. In this study, we found that miR-764-5p is up-expressed during the osteoblast differentiation in calvarial and osteoblast progenitor cells, coupled with down-expression of CHIP protein. We observed that forced expression or inhibition of miR-764-5p decreased or increased the CHIP protein level through affecting its translation by targeting the 3'-UTR region. Perturbation of miR-764-5p resulted in altered differentiation fate of osteoblast progenitor cells and the role of miR-764-5p was reversed by overexpression of CHIP, whereas depletion of CHIP impaired the effect of miR-764-5p. Our data showed that miR-764-5p positively regulates osteoblast differentiation from osteoblast progenitor cells by repressing the translation of CHIP protein. (c) 2012 American Society for Bone and Mineral Research.