MiR-149-3p Regulates the Switch Between Adipogenic and Osteogenic Differentiation of BMSCs by Targeting FTO

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have been suggested to have the capacity to differentiate into different cell lineages. Maintaining a balanced stem cell differentiation program is crucial to the bone microenvironment and bone development. MiRNAs have played a critical role in regulating the differentiation of BMSCs into particular lineage. However, the role of miR-149-3p in the adipogenic and osteogenic differentiation of BMSCs has not been extensively discovered. In this study, we aimed to detect the expression levels of miR-149-3p during the differentiation of BMSCs and investigate whether miR-149-3p participated in the lineage choice of BMSCs or not. Compared to mimic-NC, miR-149-3p mimic made the adipogenic differentiation potential of BMSCs decreased and the osteogenic differentiation potential increased. Luciferase reporter assay further revealed that miR-149-3p repressed the expression of fat mass and obesity-associated (FTO) gene through binding to the 3ʹ-untranslated region (3ʹ-UTR) of the FTO mRNA. And the role of miR-149-3p in inhibiting adipogenic lineage differentiation and potentiating osteogenic lineage differentiation were mainly through targeting FTO, which also played an important role in regulating body weight and fat mass. We found that miR-149-3p regulated the differentiation of BMSCs by repressing FTO. In addition, BMSCs treated with miR-149-3p AMO exhibited higher potential to differentiate into adipocytes and lower tendency to differentiate into osteoblasts compared to BMSCs transfected with negative control. In summary, our results detected the effects of miR-149-3p in cell fate specification of BMSCs, and revealed that miR-149-3p inhibited the adipogenic differentiation of BMSCs via a miR-149-3p/FTO regulatory axis. This study provides cellular and molecular insights into the observation that miR-149-3p is a prospective candidate gene for BMSCs-based bone tissue engineering in treating osteoporosis. Funding Statement: This work was supported by grants from the Natural Science Foundation of China (81501920/81573434/81800784), the Postdoctoral Science Foundation of China (2018M630370)，the Heilongjiang Postdoctoral Fund (LBH-Z17134) Declaration of Interests: The authors indicate no potential conflicts of interest Ethics Approval Statement: All animal procedures were approved by the Animal Experimental Ethic Committee of Harbin Medical University