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Inhibiting effect of microRNA-187-3p on osteogenic differentiation of osteoblast precursor cells by suppressing cannabinoid receptor type 2
Differentiation ( IF 2.2 ) Pub Date : 2019-07-13 , DOI: 10.1016/j.diff.2019.07.002
Aihua Xu , Yang Yang , Yang Shao , Meng Wu , Yongxin Sun

Induction of osteoblast differentiation is an effective approach in promoting osteoblastogenesis and bone formation. MicroRNA (miR) is a kind of small regulatory RNA molecules that control both physiological and pathological processes. The purpose of this research was to explore the function of miR-187-3p in proliferation and osteogenic differentiation in human osteoblastic precursor cells (hFOB 1.19). Our results showed a significant promotion of cell proliferation by miR-187-3p in hFOB 1.19 cell accompanied by increased proliferating cell nuclear antigen (PCNA) and Ki67 expression, whereas miR-187-3p knockdown led to an inhibition of cell proliferation. Moreover, our data revealed that miR-187-3p was decreased in hFOB 1.19 cells undergoing osteoblastic differentiation. Silencing of miR-187-3p dramatically accelerated hFOB 1.19 osteoblastic differentiation, as evidenced by the increase of alkaline phosphatase (ALP) activity and calcium deposition, as well as elevated osteopontin (OPN), collagen type I alpha 1 (COL1A1), and bone sialoprotein (BSP) gene expression, whereas overexpression of miR-187-3p suppressed osteoblastic differentiation. Furthermore, we demonstrated that miR-187-3p could inhibit cannabinoid receptor type 2 (CNR2) expression by targeting its 3’ untranslated region (UTR). Upregulation of CNR2 inversed the inhibiting influence of miR-187-3p on hFOB 1.19 osteogenic differentiation. Collectively, our results showed a pivotal role of miR-187-3p/CNR2 axis in osteoblastic differentiation, indicating that miR-187-3p may serve as a promising target in the therapy of osteoporosis.



中文翻译:

microRNA-187-3p通过抑制2型大麻素受体对成骨细胞前体细胞成骨分化的抑制作用

诱导成骨细胞分化是促进成骨细胞生成和骨形成的有效方法。MicroRNA(miR)是一类小的调节性RNA分子,可同时控制生理和病理过程。这项研究的目的是探讨miR-187-3p在人成骨细胞前体细胞(hFOB 1.19)中的增殖和成骨分化中的功能。我们的研究结果显示,miR-187-3p在hFOB 1.19细胞中显着促进了细胞增殖,并伴随着增殖细胞核抗原(PCNA)和Ki67表达的增加,而miR-187-3p的敲低导致细胞增殖的抑制。此外,我们的数据显示,经历成骨细胞分化的hFOB 1.19细胞中miR-187-3p降低。沉默miR-187-3p可显着加速hFOB 1。19的成骨细胞分化,如碱性磷酸酶(ALP)活性和钙沉积增加,以及骨桥蛋白(OPN),I型胶原Iα1(COL1A1)和骨唾液蛋白(BSP)基因表达升高所证明,而过表达miR-187-3p抑制成骨细胞分化。此外,我们证明了miR-187-3p可以通过靶向其3'非翻译区(UTR)来抑制2型大麻素受体(CNR2)的表达。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。碱性磷酸酶(ALP)活性和钙沉积的增加,以及骨桥蛋白(OPN),I型胶原蛋白Iα1(COL1A1)和骨唾液蛋白(BSP)基因表达的增加证明了这一点,而miR-187- 3p抑制成骨细胞分化。此外,我们证明了miR-187-3p可以通过靶向其3'非翻译区(UTR)来抑制2型大麻素受体(CNR2)的表达。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。如碱性磷酸酶(ALP)活性和钙沉积的增加,以及骨桥蛋白(OPN),I型胶原1型胶原(COL1A1)和骨唾液蛋白(BSP)基因表达升高所证明,而miR-187- 3p抑制成骨细胞分化。此外,我们证明了miR-187-3p可以通过靶向其3'非翻译区(UTR)来抑制2型大麻素受体(CNR2)的表达。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。和骨唾液蛋白(BSP)基因表达,而miR-187-3p的过表达抑制成骨细胞分化。此外,我们证明了miR-187-3p可以通过靶向其3'非翻译区(UTR)来抑制2型大麻素受体(CNR2)的表达。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。和骨唾液蛋白(BSP)基因表达,而miR-187-3p的过表达抑制成骨细胞分化。此外,我们证明了miR-187-3p可以通过靶向其3'非翻译区(UTR)来抑制2型大麻素受体(CNR2)的表达。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。CNR2的上调逆转了miR-187-3p对hFOB 1.19成骨分化的抑制作用。总体而言,我们的研究结果表明miR-187-3p / CNR2轴在成骨细胞分化中起着关键作用,表明miR-187-3p可能在骨质疏松症治疗中有望成为靶标。

更新日期:2019-07-13
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