miR-148a-3p regulates adipocyte and osteoblast differentiation by targeting lysine-specific demethylase 6b
miR-148a-3p regulates adipocyte and osteoblast differentiation by targeting lysine-specific demethylase 6b
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miR-148a-3p 通过靶向赖氨酸特异性去甲基化酶 6b 调节脂肪细胞和成骨细胞分化
DOI：
10.1016/j.gene.2017.06.002
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发表时间：
2017-09-05
期刊：
影响因子：
3.5
通讯作者：
Wang, Baoli
中科院分区：
文献类型：
--
作者：
Tian, Lijie;Zheng, Fang;Wang, Baoli
最近对间充质干细胞向脂肪细胞和成骨细胞转变的mirna的研究为理解脂肪形成和成骨的分子基础提供了新的见解。目前的研究表明，miR-148a-3p在原代培养的骨髓基质细胞和建立的基质ST2细胞系中经过成脂和/或成骨处理后发生改变。补充miR-148a-3p活性抑制细胞生长，诱导ST2分化为成熟脂肪细胞。相反，内源性miR-148a-3p的失活抑制了ST2的完全分化。相比之下，补充miR-148a-3p会减弱成骨细胞的分化。赖氨酸特异性去甲基化酶6b （Kdm6b）是最近发现的成骨细胞分化调节剂，通过荧光素酶测定显示是miR-148a-3p的直接靶标。Kdm6b的过表达减弱了miR-148a-3p对脂肪生成分化的刺激。综上所述，我们的研究提供了miR-148a-3p通过直接靶向Kdm6b相互调节脂肪细胞和成骨细胞分化的证据。
Recent emerging studies of miRNAs in mesenchymal stem cell commitment toward adipocyte and osteoblast provide new insights for the understanding of the molecular basis of adipogenesis and osteogenesis. The current study revealed that miR-148a-3p was altered in primary cultured marrow stromal cells and established stromal ST2 line after adipogenic and/or osteogenic treatment. Supplementing miR-148a-3p activity inhibited cell growth and induced ST2 to differentiate into mature adipocytes. Conversely, inactivation of the endogenous miR-148a-3p suppressed ST2 to fully differentiate. By contrast, supplementation of the miR-148a-3p blunted osteoblast differentiation. Lysine-specific demethylase 6b (Kdm6b), a recently identified regulator of osteoblast differentiation was shown to be a direct target of miR-148a-3p by using the luciferase assay. Overexpression of Kdm6b attenuated miR-148a-3p stimulation of adipogenic differentiation. Taken together, our study provides evidences that miR-148a-3p reciprocally regulates adipocyte and osteoblast differentiation through directly targeting Kdm6b.