miR-142-5p promotes the osteoclast differentiation of bone marrow-derived macrophages via PTEN/PI3K/AKT/FoxO1 pathway
miR-142-5p promotes the osteoclast differentiation of bone marrow-derived macrophages via PTEN/PI3K/AKT/FoxO1 pathway
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DOI：
10.1007/s00774-019-00997-y
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发表时间：
2019-09-01
影响因子：
3.3
通讯作者：
Zhang, Xinliang
中科院分区：
文献类型：
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作者：
Lou, Zhenkai;Peng, Zhi;Zhang, Xinliang
microRNAs（miRNAs）是一类重要的调控因子，参与了人类多种疾病的发生发展。然而，miR-142- 5 p对骨髓源性巨噬细胞（BMSCs）破骨细胞分化的潜在作用和机制尚未阐明。本研究的目的是探讨Besides调控破骨细胞生成的分子机制，为骨相关疾病的治疗提供更有效的方法。在本研究中，从大鼠中分离并培养了双歧杆菌。此外，使用NF-kB配体的受体激活剂来诱导破骨细胞分化。此外，我们还分析了miR-142- 5 p模拟物/抑制剂对Bcells破骨细胞生成的影响。结果表明，下调miR-142- 5 p表达可抑制BMSCs的破骨细胞生成，而过表达则可促进破骨细胞生成。研究证实PTEN是miR-142- 5 p的直接靶点，并探讨其对破骨细胞生成的影响。最重要的是，LY 29004（PI 3 k/Akt通路的抑制剂）的处理可以减弱miR-142- 5 p破骨细胞生成作用，而LY 29004对破骨细胞生成的抑制作用通过FoxO 1的敲低而消除。综上所述，我们的研究结果表明，miR-142- 5 p通过PI 3 k/Akt/FoxO 1途径通过靶向PTEN促进BclB的破骨细胞生成。
It is increasingly recognized that microRNAs (miRNAs) are a kind of important regulators, which are involved in the pathogenesis and development of various human diseases. However, the underlying effects and mechanism of miR-142-5p on the osteoclast differentiation of bone marrow-derived macrophages (BMMs) have not been elucidated. The aim of the present study is to explore the molecular mechanisms that regulate the osteoclastogenesis of BMMs for providing more efficient methods for treating bone-related diseases. In the present study, BMMs were isolated from rats and cultured. Moreover, receptor activators of NF-kB ligands were used to induce the osteoclast differentiation of BMMs. Furthermore, we analyzed the effects of miR-142-5p mimics/inhibitor on the osteoclastogenesis of BMMs. The results indicated that the downregulation of miR-142-5p inhibited the osteoclastogenesis of BMMs, whereas the overexpression enhanced this process. PTEN was testified to be a direct target of miR-142-5p, and its effects on the osteoclastogenesis were also described. Most importantly, treatment of LY29004 (an inhibitor of the PI3k/Akt pathway) can attenuate miR-142-5p osteoclastogenesis effects, while the inhibition effects of LY29004 on the osteoclastogenesis were abolished by knockdown of FoxO1. Taken together, our findings demonstrated that miR-142-5p promotes the osteoclastogenesis of BMMs through PI3k/Akt/FoxO1 pathway via targeting PTEN.