miR-214对骨代谢调控作用的研究进展

Research advances in the regulatory effect of miR-214 on bone metabolism

骨骼中各种细胞受到严格调控以维持骨骼的动态平衡,调控异常会导致骨质疏松、骨关节炎、骨折愈合迟缓等疾病的发生。MicroRNA是一种非编码RNA,作为骨代谢的关键调控因子,可参与调控骨髓间充质干细胞、成骨细胞、骨细胞、破骨细胞和软骨细胞的增殖、分化和功能,进而影响骨代谢的平衡。研究表明miR-214可通过其靶基因β-连环蛋白、激活转录因子4、成纤维细胞生长因子受体、c-Jun氨基末端激酶、p38、锌指结构转录因子、同源性磷酸酶-张力蛋白等影响骨代谢,同时在骨肉瘤、骨质疏松等骨代谢疾病中miR-214也可通过细胞粘附因子1、亮氨酸拉链推定肿瘤抑制因子1以及相关的骨代谢调控因子影响疾病发展进程和预后。此外最新研究表明自噬相关基因12和γ-氨基丁酸A型受体也是miR-214的靶基因,miR-214也可能通过调控骨细胞自噬来影响骨代谢。因此本文通过综述国内外有关miR-214与骨代谢的相关报道,旨在阐明miR-214的调控机制。

Various cells in the bone are strictly regulated to maintain bone homoeostasis.Abnormal regulation leads to many bone diseases such as osteoporosis,osteoarthritis,and delayed fracture healing.MicroRNA,a type of non-coding RNAs,is a key regulator of bone metabolism and involved in the regulation of proliferation,differentiation,and function of bone marrow mesenchymal stem cells,osteoblasts,bone cells,osteoclasts,and chondrocytes,thereby affecting the homoeostasis of bone metabolism.Previous studies have demonstrated that miR-214 affects bone metabolism by targeting genes such asβ-catenin,activating transcription factor 4,fibroblast growth factor receptor 1,c-Jun N-terminal kinase,p38,Osterix,and phosphatase and tensin homolog.Moreover,miR-214 has an impact on the development,progression,and prognosis of some bone metabolism diseases such as osteosarcoma and osteoporosis via cell adhesion molecule 1,Rho-associated coiled-coil kinase 1,and other related bone metabolism regulators.Recent studies have shown that two autophagy-related genes,autophagy-related gene 12 and GABAA-receptor-associated protein,are also target genes of miR-214,suggesting that miR-214 may affect bone metabolism by regulating autophagy of bone cells.This article aims to elucidate the regulatory mechanism of miR-214 by reviewing domestic and international literature on miR-214 and bone metabolism.