LncRNA metastasis-associated lung adenocarcinoma transcript-1 promotes osteogenic differentiation of bone marrow stem cells and inhibits osteoclastic differentiation of Mempty set in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/beta-catenin axis

被引:21
|
作者
Li, Xiangxin [1 ]
机构
[1] Changchun Univ Tradit Chinese Med, Affiliated Hosp, Dept Pain, 1478 Gongnong Rd, Changchun 130021, Jilin, Peoples R China
关键词
competitive endogenous RNA; IGF2BP1; lncRNA MALAT1; miR-124-3p; osteoclastic differentiation; osteogenic differentiation; osteoporosis; Wnt/beta catenin pathway; CLINICAL-PRACTICE GUIDELINES; POSTMENOPAUSAL OSTEOPOROSIS; OSTEOBLAST DIFFERENTIATION; METABOLISM; EXPRESSION; DENOSUMAB; SKELETAL; PATHWAY; GROWTH; WOMEN;
D O I
10.1002/term.3279
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Osteoporosis is defined as a skeletal disorder characterized by impairment in bone strength. The potential application of lncRNAs as therapeutic targets for osteoporosis has been unveiled. This study investigated the regulatory mechanism of lncRNA MALAT1 in the differentiation of bone marrow stem cells (BMSCs) and macrophages (Mempty set) in osteoporosis. MALAT1 expression in peripheral blood of elderly osteoporosis patients and healthy volunteers was detected. BMSCs and mononuclear Mempty set were isolated and cultured. Osteogenic differentiation of BMSCs and osteoclastic differentiation of Mo were induced. BMSCs and Mempty set were transfected with si-MALAT1, miR-124-3p mimics, miR-124-3p inhibitor, or pcDNA IGF2 BP1, followed by detection of cell differentiation. The target microRNAs (miRs) and downstream genes and signaling pathways of MALAT1 were examined. The ovariectomy-induced mouse model of osteoporosis was established, and the mice were injected with pcDNAMALAT1. MALAT1 was downregulated in osteoporosis patients, increased in BMSCs after osteogenic differentiation, and diminished in Mempty set after osteoclastic differentiation. Downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mempty set. MALAT1 upregulated IGF2BP1 expression by competitively binding to miR-124-3p. miR-124-3p silencing reversed the effect of si-MALAT1 on BMSCs and Mempty set differentiation, and IGF2BP1 upregulation averted the effect of overexpressed-miR-124-3p by activating the Wnt/beta-catenin pathway. Upregulation of MALAT1 activated the Wnt/beta-catenin pathway and attenuated bone injury in mice. In conclusion, IncRNA MALAT1 promoted the osteogenic differentiation of BMSCs and inhibited osteoclastic differentiation of Mo in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/beta-catenin axis.
引用
收藏
页码:311 / 329
页数:19
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