长链非编码 RNA MEG3 通过靶向 miR-133a-3p 抑制绝经后骨质疏松症骨髓间充质干细胞的成骨分化。
LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p.
机构信息
Department of Gerontology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.
Institute of Hard Tissue Development and Regeneration of Harbin Medical University, Harbin; 150086, China; Heilongjiang Academy of Medical Sciences, Harbin 150001, Heilongjiang, China.
出版信息
Biomed Pharmacother. 2017 May;89:1178-1186. doi: 10.1016/j.biopha.2017.02.090. Epub 2017 Mar 14.
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.
背景与目的
长链非编码 RNA（lncRNA）MEG3 已被证明是参与各种人类疾病发病机制和发展的重要调节因子。然而，MEG3 在绝经后骨质疏松症（PMOP）中的功能作用及其机制尚不清楚。
方法
分别从 PMOP 患者和模型鼠的骨髓间充质干细胞（BMSCs）中分离和培养 BMSCs，采用 qRT-PCR 检测 BMSCs 中 MEG3 和 miR-133a-3p 的表达。构建重组表达载体并转染 BMSCs 以调节 MEG3 和 miR-133a-3p 的内源性表达。矿化结节形成、碱性磷酸酶（ALP）活性以及 Runx2、OCN、OPN 的表达被用作成骨细胞分化的特异性标记物。
结果
PMOP 患者 BMSCs 中 MEG3 和 miR-133a-3p 的表达增加，且 BMSCs 中 MEG3 和 miR-133a-3p 的表达呈正相关。在 BMSCs 向成骨细胞分化过程中，MEG3 和 miR-133a-3p 的表达明显下调，过表达 MEG3 可逆转成骨诱导引起的 miR-133a-3p 下调，同时 SLC39A1 表达显著下降。此外，miR-133a-3p 的沉默或上调通过直接结合消除了 MEG3 对 BMSCs 成骨分化的影响。
结论
该研究表明，MEG3 调节 miR-133a-3p 的表达，并抑制 PMOP 诱导的 BMSCs 成骨分化。
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