LncRNA HOTAIRM1 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting miR-152-3p/ETS1 axis.

Background: Bone marrow mesenchymal stem cells (BMSCs) can differentiate into osteoblasts and thus present a tremendous therapeutic potential in osteoporosis. Here, we elucidated the involvement of long non-coding RNAs (lncRNAs) HOXA transcript antisense RNA, myeloid-specific 1 (HOTAIRM1) in the osteogenic differentiation of BMSCs.
Methods and Results: The expression levels of HOTAIRM1, miR-152-3p, ETS proto-oncogene 1 (ETS1), runt-related transcription factor 2 (RUNX2), Osterix, and osteocalcin (OCN) were determined by a quantitative real-time polymerase chain reaction (qRT-PCR) or western blot method. Targeted relationship between miR-152-3p and HOTAIRM1 or ETS1 was confirmed by dual-luciferase reporter and RNA pull-down assays. The activity of alkaline phosphatase (ALP) was measured by the ALP Activity Assay Kit. The extent of the calcium deposition was assessed by Alizarin Red Staining. Our data showed that HOTAIRM1 and ETS1 levels were up-regulated and miR-152-3p expression was down-regulated during osteogenic differentiation of human BMSCs (HBMSCs). HOTAIRM1 overexpression enhanced osteogenic differentiation of HBMSCs, and decreased level of HOTAIRM1 suppressed osteogenic differentiation of HBMSCs. HOTAIRM1 directly targeted miR-152-3p. ETS1 was identified as a direct and functional target of miR-152-3p. Furthermore, HOTAIRM1 functioned as a post-transcriptional regulator of ETS1 expression by miR-152-3p.
Conclusion: The findings in this paper identify HOTAIRM1 as a novel regulator of osteogenic differentiation of BMSCs by the regulation of miR-152-3p/ETS1 axis, uncovering HOTAIRM1 as a promising therapeutic strategy for osteoporosis.
(© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)