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

• Published in: Biomedicine & pharmacotherapy Vol. 89; pp. 1178 - 1186
• Main Authors: Wang, Qiujun, Li, Ying, Zhang, Yuanxia, Ma, Lan, Lin, Lin, Meng, Jia, Jiang, Lihong, Wang, Liping, Zhou, Ping, Zhang, Yina
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2017
• Subjects: Animals; Bone Marrow Cells - physiology; Bone marrow mesenchymal stem cells (BMSCs); Cation Transport Proteins - genetics; Cell Differentiation - genetics; Cells, Cultured; Down-Regulation - genetics; Female; Humans; Internal Medicine; LncRNA MEG3; Medical Education; Mesenchymal Stromal Cells - physiology; Mice; Mice, Inbred BALB C; MicroRNAs - genetics; miR-133a-3p; Osteoblasts - physiology; Osteogenesis - genetics; Osteogenic differentiation; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - genetics; Postmenopausal osteoporosis (PMOP); RNA, Long Noncoding - genetics; miR-133a-3p; LncRNA MEG3; Bone marrow mesenchymal stem cells (BMSCs); Osteogenic differentiation; Postmenopausal osteoporosis (PMOP)
• DOI: 10.1016/j.biopha.2017.02.090
• ISSN: 0753-3322

Abstract 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.