单位：[a]Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing,[b]Department of Orthopedics, Bayannaoer City Hospital, Bayannaoer City,[c]Department of Orthopedics, China-Japan Friendship Hospital,Beijing University of Chinese Medicine, Beijing, China
Background/Aims: Osteoporosis is a bone metabolic disease characterized by a systemic impairment of bone mass, which results in increased propensity of fragility fractures. A reduction in the differentiation of MSCs into osteoblasts contributes to the impaired bone formation observed in osteoporosis. Mesenchymal stem cells (MSCs) are induced to differentiate into preosteoblasts, which are regulated by the signaling cascades initiated by the various signals, including miRNAs. miR-16-2* is a newly discovered miRNA that participates in diagnosis and prognosis of hepatocellular carcinoma, cervical cancer and chronic lymphocytic leukemia. However, the effect of miR-16-2* on the regulation of osteoblast differentiation and the mechanism responsible are still unclear. Here we discuss the contribution of miR-162* to osteoporosis, osteoblast differentiation and mineralization. Methods: The expression pattern of miR-16-2* during osteogenesis or in osteoporosis bone samples was validated by quantitative real-time PCR (qRT-PCR). The human bone marrow mesenchymal stem cells (hBMSCs) were induced to differentiate into osteoblasts by osteogenic induced medium containing dexamethasone, ascorbate-2-phosphat, beta-glycerophosphate and vitamin-D3. The target genes of miR-16-2* were predicted by TargetScan and PicTar. The mRNA and protein levels of osteogenic key markers were detected using qRT-PCR or western blot respectively. The WNT signal activity was analyzed by TOP/FOP reporter assay. Results: The expression of miR-16-2* in patient bone tissue with osteoporosis was negatively correlated with bone formation related genes. During osteoblast differentiation process, the expression of miR-162* was significantly decreased. Upregulation of miR-16-2* in hBMSCs impaired the osteogenic differentiation while the downregulation of miR-16-2* increased this process. Upregulation the expression of miR-16-2* could also block the WNT signal pathway by directly target WNT5A. Furthermore, knockdown of miR-16-2* could promote the activation of RUNX2, possibly by lifting the inhibitory effect of miR-16-2* on WNT pathway. Conclusion: Taken together, we report a novel biological role of miR-16-2* in osteogenesis through regulating WNT5A response for the first time. Our data support the potential utilization of miRNA-based therapies in regenerative medicine. (C) 2018 The Author(s) Published by S. Karger AG, Basel
第一作者单位：[a]Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing,[b]Department of Orthopedics, Bayannaoer City Hospital, Bayannaoer City,
共同第一作者：
通讯作者：
通讯机构：[a]Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing,[*1]Department of Orthopedics, Dongzhimen Hospital, Beijing University of Chinese Medicine NO.5 Haiyuncang Street, Dong cheng District, Beijing100700 (China)
推荐引用方式(GB/T 7714)：
Lijun Duan,He Zhao,Yang Xiong,et al.miR-16-2*Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells[J].CELLULAR PHYSIOLOGY and BIOCHEMISTRY.2018,51(3):1087-1102.doi:10.1159/000495489.
APA：
Lijun Duan,He Zhao,Yang Xiong,Xiangsheng Tang,Yongdong Yang...&Xing Yu.(2018).miR-16-2*Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells.CELLULAR PHYSIOLOGY and BIOCHEMISTRY,51,(3)
MLA：
Lijun Duan,et al."miR-16-2*Interferes with WNT5A to Regulate Osteogenesis of Mesenchymal Stem Cells".CELLULAR PHYSIOLOGY and BIOCHEMISTRY 51..3(2018):1087-1102
