LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p

被引:180
|
作者
Wang Qiujun [1 ]
Li Ying [2 ,3 ]
Zhang Yuanxia [1 ]
Ma Lan [1 ]
Lin Lin [1 ]
Meng Jia [1 ]
Jiang Lihong [1 ]
Wang Liping [1 ]
Zhou Ping [1 ]
Zhang Yina [1 ]
机构
[1] Harbin Med Univ, Affiliated Hosp 2, Dept Gerontol, Harbin 150086, Peoples R China
[2] Harbin Med Univ, Inst Hard Tissue Dev & Regenerat, Harbin 150086, Peoples R China
[3] Heilongjiang Acad Med Sci, Harbin 150001, Heilongjiang, Peoples R China
关键词
Postmenopausal osteoporosis (PMOP); Bone marrow mesenchymal stem cells (BMSCs); LncRNA MEG3; miR-133a-3p; Osteogenic differentiation; ADIPOGENIC DIFFERENTIATION; MICE;
D O I
10.1016/j.biopha.2017.02.090
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background and aims: Long non-coding RNA (lncRNA) MEG3 has proven to be an important regulator involved in the pathogenesis and development of various human diseases. However, the functional involvement of MEG3 in postmenopausal osteoporosis (PMOP) and its mechanism is still unclear. Methods: Bone marrow mesenchymal stem cells (BMSCs) were isolated and cultured from mouse pathologic models and patients with PMOP, respectively. The expression of MEG3 and miR-133a-3p in BMSCs was detected using qRT-PCR. The recombinant expression vector was constructed and transfected into BMSCs to regulate the endogenous expression of MEG3 and miR-133a-3p. The mineralized nodules formation, alkaline phosphatase (ALP) activity and Runx2, OCN, OPN expressions were used as specific markers for the differentiation of osteoblasts. Results: The expressions of MEG3 and miR-133a-3p in BMSCs from PMOP were increased, and there was a positive correlation between MEG3 and miR-133a-3p expression in BMSCs. In the differentiation process from BMSCs to osteoblasts, the expressions of MEG3 and miR-133a-3p were markedly decreased, and MEG3 overexpression reversed the osteogenic induction-mediated downregulation of miR-133a-3p, which was accompanied by significant decline in SLC39A1 expression. Furthermore, miR-133a-3p silencing or upregulation eliminated the effects of MEG3 on the osteogenic differentiation of BMSCs through direct binding. Conclusions: The research indicated that MEG3 regulated the expression of miR-133a-3p, and inhibited the osteogenic differentiation of BMSCs induced PMOP. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:1178 / 1186
页数:9
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