miR-33a-5p modulates TNF-α-inhibited osteogenic differentiation by targeting SATB2 expression in hBMSCs
miR-33a-5p modulates TNF-α-inhibited osteogenic differentiation by targeting SATB2 expression in hBMSCs
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DOI：
10.1002/1873-3468.12064
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发表时间：
2016-02-01
期刊：
影响因子：
3.5
通讯作者：
Huang, Hui
中科院分区：
文献类型：
--
作者：
Mi, Wenxiang;Shi, Qiongling;Huang, Hui
mirna在骨骼中发挥多种作用，包括介导炎症的病理作用。这里，我们发现在bmp -2诱导的hBMSCs成骨分化过程中，tnf - α治疗后miR-33a-5p表达显著增加。荧光素酶报告基因检测和western blotting表明，特殊的富含at的序列结合蛋白2 （SATB2）是miR-33a-5p的靶标。此外，我们发现BMP-2通过BMP-2- runx2途径直接与SATB2相互作用，诱导SATB2表达。然而，TNF-a首先通过抑制miR33a- 5p降解来降低SATB2的表达。因此，我们得出结论，miR-33a-5p在这个复杂的调控网络中起着核心作用。这些发现将有助于理解miR-33a-5p在炎症过程中的调节作用。
miRNAs play a number of roles in bone, including mediating the pathological effects of inflammation. Here, we found that miR-33a-5p expression was significantly increased after TNF-alpha treatment during BMP-2-induced osteogenic differentiation of hBMSCs. Luciferase reporter assays and western blotting demonstrated that special AT-rich sequence-binding protein 2 (SATB2) is a target of miR-33a-5p. Moreover, we show that BMP-2 induces SATB2 expression by interacting with SATB2 directly via the BMP-2-RUNX2 pathway. However, TNF-a first decreases SATB2 expression by inhibiting miR33a- 5p degradation. We thus conclude that miR-33a-5p plays a central role in this complex regulatory network. These findings will help to understand the regulatory role of miR-33a-5p in the inflammatory process.