lncRNA MALAT1 Mediates Osteogenic Differentiation and Apoptosis in Osteoporosis by Regulating the miR-485-5p/WNT7B Axis

Abstract

Background: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. This study aimed to investigate the effects of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation and cell apoptosis in osteoporosis. Methods: hindlimb unloading (HU) was performed to establish osteoporosis model in vivo. MicroCT was applied for pathological analysis. Microgravity (MG) was used to construct osteoporosis in vitro. The mRNA and miRNA expression was determined using RT-qPCR. Protein expression was determined using western blot. The binding sites between miR-485-5p and MALAT1/Wnt family member 7B (WNT7B) was predicted by bioinformatics analysis and verified by luciferase and RNA pull-down assays. Cellular functions were determined by ALP staining, Alizarin red staining, and flow cytometry assays. Results: MALAT1 expression was downregulated in HU mice and MG treated MC3T3-E1 cells. However, overexpression of MALAT1 upregulated the expression of Bmp4, Col1a1, Spp1, and enhanced ALP activity. Additionally, overexpression of MALAT1 inhibited apoptosis, decreased Bax and caspase-3 levels, and increased Bcl-2 level. Moreover, MALAT1 overexpression improved bone phenotype in vivo. MALAT1 functioned as a ceRNA to upregulate WNT7B. Overexpression of miR-485-5p rescued the promotion of osteogenic differentiation and the inhibition of apoptosis induced by MALAT1. Knockdown of WNT7B abolished the facilitation of osteogenic differentiation and the suppression of apoptosis induced by downregulation of miR-485-5p. Conclusion: In conclusion, MALAT1 promoted osteogenic differentiation and inhibited cell apoptosis through miR-485-5p/WNT7B axis, which suggested that MALAT1 is a potential target to alleviate osteoporosis.