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下调的 microRNA-141 通过上调 TGF-β2 促进成骨细胞活性并抑制破骨细胞活性,从而改善股骨头坏死。

Down-regulated microRNA-141 facilitates osteoblast activity and inhibits osteoclast activity to ameliorate osteonecrosis of the femoral head via up-regulating TGF-β2.

机构信息

Department of Orthopedics, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan city, Shandong, China.

出版信息

Cell Cycle. 2020 Apr;19(7):772-786. doi: 10.1080/15384101.2020.1731053. Epub 2020 Feb 23.

Abstract

Osteonecrosis of the femoral head (ONFH) is a pathological process that initially occurs in the weight-bearing field of the femoral head. Due to the unknown pathogenesis, this study was for the investigation of the effect of microRNA-141 (miR-141) targeting transforming growth factor-β2 (TGF-β2) on regulating osteoblast activity and osteoclast activity in steroid-induced ONFH.Tissues of ONFH and normal femoral head were collected for detecting the expression of miR-141 and TGF-β2. A rat model of ONFH was constructed by injection of hormones, and transfected with miR-141 inhibitors and overexpressed TGF-β2. The apoptosis of bone cells was detected by TUNEL staining. The expression of osteoprotegerin (OPG), osteoprotegerin ligand (OPGL), Bcl-2, Bax, Runx2, BMP2 and RANK were detected.Highly expressed miR-141 and lowly expressed TGF-β2 existed in femoral head tissues in ONFH. Inhibited miR-141 resulted in elevated TGF-β2 in femoral head tissues in ONFH of rats. Depressed miR-141 or overexpressed TGF-β2 inhibited the apoptosis of bone cells of rats with ONFH and induced elevated OPG, Bcl-2, BMP2, Runx2 and declined OPGL, Bax and RANK expression in the femoral head tissues of rats with ONFH.Altogether, we find that down-regulated miR-141 promotes osteoblast activity and inhibits osteoclast activity to ameliorate ONFH via up-regulated TGF-β2 expression.

摘要

股骨头坏死(ONFH)是一种最初发生在股骨头承重区域的病理过程。由于发病机制不明,本研究旨在探讨 microRNA-141(miR-141)靶向转化生长因子-β2(TGF-β2)对调节激素诱导的 ONFH 中破骨细胞和成骨细胞活性的影响。收集 ONFH 和正常股骨头组织,检测 miR-141 和 TGF-β2 的表达。通过注射激素构建大鼠 ONFH 模型,并转染 miR-141 抑制剂和过表达 TGF-β2。TUNEL 染色检测骨细胞凋亡。检测骨保护素(OPG)、骨保护素配体(OPGL)、Bcl-2、Bax、Runx2、BMP2 和 RANK 的表达。ONFH 股骨头组织中 miR-141 高表达,TGF-β2 低表达。抑制 miR-141 导致大鼠 ONFH 股骨头组织中 TGF-β2 升高。抑制 miR-141 或过表达 TGF-β2 可抑制 ONFH 大鼠骨细胞凋亡,并诱导大鼠 ONFH 股骨头组织中 OPG、Bcl-2、BMP2、Runx2 表达升高,OPGL、Bax 和 RANK 表达降低。综上所述,下调的 miR-141 通过上调 TGF-β2 的表达促进成骨细胞活性并抑制破骨细胞活性,从而改善 ONFH。

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