Qiujun Wang1, Ying Li2, Yuanxia Zhang1, Lan Ma1, Lin Lin1, Jia Meng1, Lihong Jiang1, Liping Wang1, Ping Zhou3, Yina Zhang4. 1. Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. 2. Institute of Hard Tissue Development and Regeneration of Harbin Medical University, Harbin; 150086, China; Heilongjiang Academy of Medical Sciences, Harbin 150001, Heilongjiang, China. 3. Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: zhouping121313@163.com. 4. Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: zhangyina1213@163.com.
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.
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.