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微小RNA-23b-3p通过PI3k/AKT信号通路靶向PTEN调控破骨细胞分化。

miR-23b-3p regulates differentiation of osteoclasts by targeting PTEN via the PI3k/AKT pathway.

作者信息

Chai Jiwei, Xu Liang, Liu Niansheng

机构信息

Second Ward of Trauma Surgery Department, Linyi People's Hospital, Linyi, Shandong, China.

Department of Surgery, Linyi Health School, Linyi, Shandong, China.

出版信息

Arch Med Sci. 2019 Sep 3;18(6):1542-1557. doi: 10.5114/aoms.2019.87520. eCollection 2022.

Abstract

INTRODUCTION

Osteoblasts and osteoclasts are cells of osteoblastic origin, and are vital in homeostasis of the skeleton. miRs are important for functioning, survival and differentiation of osteoclasts. It has been reported previously that miR-23b-3p is involved in osteoporosis and in regulation of differentiation of osteoblasts. It is also involved in the process of bone formation. However, the role of miR-23b-3p in differentiation of osteoclasts remains unexplored.

MATERIAL AND METHODS

CSF-1 and ODF induced osteoclasts were used for the study. RNA isolation was done from TIB-71 cells. TRAP staining was done for TRAP-positive osteoclast formation. PIT assay for bone resorption was performed. For studies osteoclast-specific miR-23b-3p transgenic mice were developed.

RESULTS

The levels of miR-23b-3p were upregulated in bone marrow monocytes during osteoclastogenesis with colony stimulating factor-1 and osteoclast differentiation factor induction, which suggests that miR-23b-3p plays a crucial role in differentiation of osteoclasts. Over-expression of miR-23b-3p in bone marrow monocytes leads to osteoclastogenesis, whereas the inhibition ameliorates it. We further studied the function of miR-23b-3p via PI3K/AKT targeting the PTEN pathway. , osteoclast-specific miR-23b-3p transgenic mice showed suppressed PTEN and elevated osteoclast activity, and the mice showed decreased bone mineral density.

CONCLUSIONS

The results suggest that miR-23b-3p regulates the differentiation of osteoclasts by targeting PTEN through the PI3K/AKT cascade.

摘要

引言

成骨细胞和破骨细胞均起源于成骨细胞系,对骨骼的稳态至关重要。微小RNA(miR)对破骨细胞的功能、存活及分化具有重要作用。此前已有报道称,miR-23b-3p与骨质疏松症以及成骨细胞的分化调控有关,还参与骨形成过程。然而,miR-23b-3p在破骨细胞分化中的作用仍未得到探索。

材料与方法

本研究使用集落刺激因子-1(CSF-1)和破骨细胞分化因子(ODF)诱导的破骨细胞。从TIB-71细胞中提取RNA。进行抗酒石酸酸性磷酸酶(TRAP)染色以检测TRAP阳性破骨细胞的形成。进行骨吸收的骨陷窝分析(PIT分析)。为开展研究,构建了破骨细胞特异性miR-23b-3p转基因小鼠。

结果

在集落刺激因子-1和破骨细胞分化因子诱导破骨细胞生成过程中,骨髓单核细胞中miR-23b-3p的水平上调,这表明miR-23b-3p在破骨细胞分化中起关键作用。骨髓单核细胞中miR-23b-3p的过表达导致破骨细胞生成,而抑制其表达则可改善这一情况。我们进一步通过靶向PTEN途径的PI3K/AKT研究了miR-23b-3p的功能。破骨细胞特异性miR-23b-3p转基因小鼠显示PTEN受到抑制,破骨细胞活性升高,且小鼠骨密度降低。

结论

结果表明,miR-23b-3p通过PI3K/AKT级联靶向PTEN来调节破骨细胞的分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81e4/9710281/23a15e8e1336/AMS-18-6-110286-g001.jpg

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