Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop.
Vaspin regulates the osteogenic differentiation of MC3T3-E1 through the PI3K-Akt/miR-34c loop.
复制标题
Vaspin 通过 PI3K-Akt/miR-34c 环调节 MC3T3-E1 的成骨分化
DOI：
10.1038/srep25578
复制
发表时间：
2016-05-09
影响因子：
4.6
通讯作者：
Yuan LQ
中科院分区：
文献类型：
--
作者：
Liu Y;Xu F;Pei HX;Zhu X;Lin X;Song CY;Liang QH;Liao EY;Yuan LQ
Vaspin（内脏脂肪组织来源的丝氨酸蛋白酶抑制剂）是一种新发现的脂肪因子，广泛参与糖尿病、多囊卵巢综合征等代谢紊乱。然而，vaspin对成骨的调控作用及其机制尚不清楚。在此，我们发现vaspin可以以剂量依赖性方式减弱前成骨细胞系MC 3 T3-E1的成骨分化;在此过程中，miRNA-34 c（miR-34 c）的表达显著增加。在MC 3 T3-E1中下调miR-34 c的表达减弱了vaspin的成骨抑制作用，而上调miR-34 c通过其靶基因Runx 2增加了这种作用。同时，我们发现vaspin还可以激活PI 3 K-Akt信号通路。用特异性抑制剂阻断PI 3 K-Akt信号通路可降低vaspin的成骨抑制作用以及miR-34 c的表达水平。此外，敲低miR-34 c可以促进Akt的激活，这可能是通过靶向c-met表达来实现的。因此，PI 3 K-Akt和miR-34 c构成了一个调节环，并控制彼此的表达。综上所述，我们的研究表明vaspin在体外能够抑制成骨细胞的分化，PI 3 K-Akt/miR-34 c环可能是其抑制成骨细胞分化的机制之一。
Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a newly discovered adipokine that widely participates in diabetes mellitus, polycystic ovarian syndrome and other disorders of metabolism. However, the effect of vaspin on the regulation of osteogenesis and the mechanism responsible are still unclear. Here, we found that vaspin can attenuate the osteogenic differentiation of the preosteoblast cell line MC3T3-E1 in a dose-dependent way; also, during this process, the expression of miRNA-34c (miR-34c) was significantly increased. Down-regulation of the expression of miR-34c in MC3T3-E1 diminished the osteogenic inhibitory effect of vaspin, while the up-regulation of miR-34c increased this effect through its target gene Runx2. Meanwhile, we found that vaspin could also activate the PI3K-Akt signalling pathway. Blocking the PI3K-Akt signalling pathway with specific inhibitors could decrease the osteogenic inhibitory effect of vaspin as well as the expression level of miR-34c. Furthermore, knock-down of miR-34c could promote the activation of Akt, which was probably realised by targeting c-met expression. Thus, PI3K-Akt and miR-34c constituted a modulation loop and controlled the expression of each other. Taken together, our study showed that vaspin could inhibit the osteogenic differentiationin vitro, and the PI3K-Akt/miR-34c loop might be the underlying mechanism.