MicroRNA-375 Inhibits Bone Marrow Mesenchymal Stem Cells Osteogenic Differentiation by Targeting The-Eleven Translocation-2 in Aplastic Anemia

Abstract

Aplastic anemia (AA) is a potentially life-threatening disease and the exact mechanism is still unclear. Herein, we aimed to investigate whether microRNA (miRNA)-375 participates in BMSCs osteogenic differentiation in AA. BMSCs were collected from AA patients to detect the expression of miR-375. BMSCs were transfected with plasmids, followed by analysis of osteogenic differentiationrelated genes by western blot and RT-qPCR, Alkaline phosphatase (ALP) activity and the correlation between miR-375 and TET2. miR-375 was significantly upregulated in BMSCs. Transfection of miR-375 inhibitor significantly enhanced BMSCs osteogenic differentiation.On the contrary, upregulation of miR-375 alleviated BMSC osteogenic differentiation. miR-375 was indicated to target and inhibit TET2 in BMSCs, and reduction of TET2 was accompanied with decreased 5-hydroxymethylcytosine and osteogenic gene expression. Interestingly, TET2 knockdown inhibited osteogenic capacity and TET2 upregulation reversed miR-375-mediated inhibition of BMSC differentiation.miR-375 mitigates BMSCs osteogenic ability in AA by inhibiting TET2, indicating a novel miR-375-based therapeutic strategy for AA.