Department of Anesthesiology, The First Hospital of Jilin University, Changchun, 130000, Jilin, China.
Department of Orthopaedics, The First Hospital of Jilin University, Changchun, 130000, Jilin, China.
Mol Cell Endocrinol. 2019 Oct 1;496:110534. doi: 10.1016/j.mce.2019.110534. Epub 2019 Aug 6.
Studies have shown that promoting the differentiation of bone marrow mesenchymal stem cells (BMSCs) into osteoblasts could protect against osteoporosis. Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) participate in BMSC osteogenic differentiation. This study aimed to investigate the role and underlying mechanism of growth arrest-specific transcript 5 (GAS5) in osteogenic differentiation. The mechanism was mainly focused on miR-135a-5p/FOXO1 pathway by gain- and loss-of function tests. GAS5 and FOXO1 expression was decreased, whereas miR-135a-5p expression was increased, in the BMSCs from osteoporotic mice. Levels of GAS5 and FOXO1 were increased and miR-135a-5p expression was decreased during osteogenic differentiation of BMSCs. Overexpression of GAS5 promoted, whereas knockdown of GAS5 suppressed, BMSC osteogenic differentiation. As for the mechanism, GAS5 functioned as a competing endogenous RNA for miR-135a-5p to regulate FOXO1 expression. In conclusion, GAS5 promoted osteogenesis of BMSCs by regulating the miR-135a-5p/FOXO1 axis. This finding suggests that targeting GAS5 may be a useful therapy for treating postmenopausal osteoporosis.
研究表明，促进骨髓间充质干细胞（BMSCs）向成骨细胞分化可预防骨质疏松症。越来越多的证据表明，长非编码 RNA（lncRNAs）参与 BMSC 成骨分化。本研究旨在探讨生长停滞特异性转录物 5（GAS5）在成骨分化中的作用及其潜在机制。通过增益和缺失功能测试，主要关注 miR-135a-5p/FOXO1 通路的机制。在骨质疏松症小鼠的 BMSCs 中，GAS5 和 FOXO1 的表达降低，而 miR-135a-5p 的表达增加。在 BMSCs 的成骨分化过程中，GAS5 和 FOXO1 的水平增加，而 miR-135a-5p 的表达减少。GAS5 的过表达促进了 BMSC 成骨分化，而 GAS5 的敲低则抑制了 BMSC 成骨分化。就其机制而言，GAS5 作为 miR-135a-5p 的竞争性内源性 RNA 调节 FOXO1 的表达。总之，GAS5 通过调节 miR-135a-5p/FOXO1 轴促进 BMSCs 的成骨作用。这一发现表明，靶向 GAS5 可能是治疗绝经后骨质疏松症的一种有效方法。
