LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p.
OBJECTIVE
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.
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Qiujun
Q
Wang
Institute of Hard Tissue Development and Regeneration of Harbin Medical University, Harbin; 150086, China; Heilongjiang Academy of Medical Sciences, Harbin 150001, Heilongjiang, China.
Ying
Y
Li
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Yuanxia
Y
Zhang
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Lan
L
Ma
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Lin
L
Lin
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Jia
J
Meng
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Lihong
L
Jiang
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Liping
L
Wang
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: zhouping121313@163.com.
Ping
P
Zhou
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address: zhangyina1213@163.com.
Yina
Y
Zhang
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D027682:Cation Transport Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000502:physiology; D010012:Osteogenesis / Q000235:genetics*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000235:genetics; D062085:RNA, Long Noncoding / Q000235:genetics*
D027682:Cation Transport Proteins; C498907:MEG3 non-coding RNA, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding
Bone marrow mesenchymal stem cells (BMSCs); LncRNA MEG3; Osteogenic differentiation; Postmenopausal osteoporosis (PMOP); miR-133a-3p