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

IF 3.1 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Tissue Engineering and Regenerative Medicine Pub Date : 2021-12-27 DOI:10.1002/term.3279

Xiangxin Li

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引用次数: 15

Abstract

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 (Mø) in osteoporosis. MALAT1 expression in peripheral blood of elderly osteoporosis patients and healthy volunteers was detected. BMSCs and mononuclear Mø were isolated and cultured. Osteogenic differentiation of BMSCs and osteoclastic differentiation of Mø were induced. BMSCs and Mø were transfected with si-MALAT1, miR-124-3p mimics, miR-124-3p inhibitor, or pcDNA IGF2BP1, 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 pcDNA-MALAT1. MALAT1 was downregulated in osteoporosis patients, increased in BMSCs after osteogenic differentiation, and diminished in Mø after osteoclastic differentiation. Downregulation of MALAT1 repressed osteogenic differentiation of BMSCs and facilitated osteoclastic differentiation of Mø. MALAT1 upregulated IGF2BP1 expression by competitively binding to miR-124-3p. miR-124-3p silencing reversed the effect of si-MALAT1 on BMSCs and Mø differentiation, and IGF2BP1 upregulation averted the effect of overexpressed-miR-124-3p by activating the Wnt/β-catenin pathway. Upregulation of MALAT1 activated the Wnt/β-catenin pathway and attenuated bone injury in mice. In conclusion, lncRNA MALAT1 promoted the osteogenic differentiation of BMSCs and inhibited osteoclastic differentiation of Mø in osteoporosis via the miR-124-3p/IGF2BP1/Wnt/β-catenin axis.

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LncRNA转移相关肺腺癌转录-1通过miR-124-3p/IGF2BP1/Wnt/β-catenin轴促进骨髓干细胞成骨分化，抑制moin骨质疏松的破骨分化

骨质疏松症是一种以骨骼强度受损为特征的骨骼疾病。lncrna作为骨质疏松症治疗靶点的潜在应用已经被揭示。本研究探讨lncRNA MALAT1在骨质疏松症中对骨髓干细胞(BMSCs)和巨噬细胞(moo)分化的调控机制。检测老年骨质疏松患者和健康志愿者外周血MALAT1的表达。分离培养骨髓间充质干细胞和单核moo细胞。诱导骨髓间充质干细胞成骨分化和moj细胞破骨分化。用si-MALAT1、miR-124-3p模拟物、miR-124-3p抑制剂或pcDNA IGF2BP1转染BMSCs和moj，然后检测细胞分化情况。研究了MALAT1的靶microrna (miRs)、下游基因和信号通路。建立卵巢切除所致小鼠骨质疏松模型，注射pcDNA-MALAT1。MALAT1在骨质疏松症患者中下调，在成骨分化后BMSCs中升高，在破骨分化后mot中降低。下调MALAT1可抑制骨髓间充质干细胞成骨分化，促进骨髓间充质干细胞破骨分化。MALAT1通过竞争性结合miR-124-3p上调IGF2BP1的表达。miR-124-3p沉默逆转了si-MALAT1对BMSCs和moj分化的影响，IGF2BP1上调通过激活Wnt/β-catenin通路避免了miR-124-3p过表达的影响。上调MALAT1激活Wnt/β-catenin通路，减轻小鼠骨损伤。综上所述，lncRNA MALAT1通过miR-124-3p/IGF2BP1/Wnt/β-catenin轴促进BMSCs成骨分化，抑制moin骨质疏松症的破骨分化。

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来源期刊

Journal of Tissue Engineering and Regenerative Medicine 生物-工程：生物医学

CiteScore

7.50

自引率

3.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Journal of Tissue Engineering and Regenerative Medicine publishes rapidly and rigorously peer-reviewed research papers, reviews, clinical case reports, perspectives, and short communications on topics relevant to the development of therapeutic approaches which combine stem or progenitor cells, biomaterials and scaffolds, growth factors and other bioactive agents, and their respective constructs. All papers should deal with research that has a direct or potential impact on the development of novel clinical approaches for the regeneration or repair of tissues and organs. The journal is multidisciplinary, covering the combination of the principles of life sciences and engineering in efforts to advance medicine and clinical strategies. The journal focuses on the use of cells, materials, and biochemical/mechanical factors in the development of biological functional substitutes that restore, maintain, or improve tissue or organ function. The journal publishes research on any tissue or organ and covers all key aspects of the field, including the development of new biomaterials and processing of scaffolds; the use of different types of cells (mainly stem and progenitor cells) and their culture in specific bioreactors; studies in relevant animal models; and clinical trials in human patients performed under strict regulatory and ethical frameworks. Manuscripts describing the use of advanced methods for the characterization of engineered tissues are also of special interest to the journal readership.