Long non-coding RNA GAS5 promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating the miR-135a-5p/FOXO1 pathway

Abstract

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.

Keywords: Bone marrow mesenchymal stem cells; FOXO1; Long non-coding RNA GAS5; Osteoblast differentiation; miR-135a-5p.