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沉默长链非编码 RNA 通过 β-连环蛋白/TCF1/Runx2 信号轴促进成骨细胞分化和骨形成。

Silencing of lncRNA Promotes Osteoblast Differentiation and Bone Formation via β-Catenin/TCF1/Runx2 Signaling Axis.

机构信息

Lab for Bone Metabolism, Key Lab for Space Biosciences and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

Research Center for Special Medicine and Health Systems Engineering, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.

出版信息

Int J Mol Sci. 2019 Dec 10;20(24):6229. doi: 10.3390/ijms20246229.

Abstract

Osteoporosis, a disease characterized by both loss of bone mass and structural deterioration of bone, is the most common reason for a broken bone among the elderly. It is known that the attenuated differentiation ability of osteogenic cells has been regarded as one of the greatest contributors to age-related bone formation reduction. However, the effects of current therapies are still unsatisfactory. In this study we identify a novel long noncoding RNA which is correlated with osteogenic differentiation and enriched in skeletal tissues of mice. In vitro analysis of bone-derived mesenchymal stem cells (BMSCs) showed that inhibited osteoblast differentiation. In vivo inhibition of by its small interfering RNA rescued bone formation in ovariectomized osteoporosis mice model. Mechanistically, inhibited the nuclear translocation of β-catenin and downregulated the expression of TCF1, LEF1, and Runx2. The results suggest that Lnc- suppresses β-catenin/TCF1/Runx2 signaling and inhibits osteoblast differentiation and bone formation, providing a novel mechanism of osteogenic differentiation and a potential drug target for osteoporosis.

摘要

骨质疏松症是一种以骨量丢失和骨结构恶化为特征的疾病,是老年人骨折最常见的原因。已知成骨细胞分化能力减弱被认为是与年龄相关的骨形成减少的最大原因之一。然而,目前的治疗效果仍然不尽如人意。在这项研究中,我们鉴定了一种与成骨分化相关的新型长非编码 RNA,该 RNA 在小鼠骨骼组织中富集。体外分析骨源性间充质干细胞(BMSCs)显示,lnc- 抑制成骨细胞分化。体内用其小干扰 RNA 抑制 lnc- 可挽救去卵巢骨质疏松症小鼠模型中的骨形成。机制上,lnc- 抑制 β-连环蛋白的核易位,并下调 TCF1、LEF1 和 Runx2 的表达。结果表明,Lnc- 抑制 β-连环蛋白/TCF1/Runx2 信号通路,抑制成骨细胞分化和骨形成,为成骨分化提供了新的机制,并为骨质疏松症提供了潜在的药物靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8ee7/6941011/121f9b8193b8/ijms-20-06229-g001.jpg

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