title: microRNA-375 inhibits osteogenic differentiation by targeting runt-related transcription factor 2.
abstract: microRNAs (miRNAs) are involved in the regulation of almost all physiological and pathological processes, including osteoblast proliferation and differentiation. miR-375 has been reported to be aberrantly expressed in various tumor types and to inhibit cell proliferation and invasion by targeting a number of key genes. However, the effects of miR-375 on osteogenic differentiation have not been investigated. Thus, the present study aimed to elucidate the function served by miR-375 in osteogenic differentiation. The expression levels of miR-375 were observed to decrease in a C2C12 cell model of osteogenic differentiation. Overexpression of miR-375 inhibited the activity of key osteoblast markers, including osteocalcin (OC), alkaline phosphatase (ALP) and collagen, type I, α 1 (COL1A1). By contrast, inhibition of miR-375 expression resulted in an increase in the osteogenic potential, as indicated by the enhanced expression levels of OC, ALP and COL1A1. In addition, a dual-luciferase reporter assay indicated that runt-related transcription factor 2 (RUNX2) was a target of miR-375. Western blot analysis revealed that the inhibition of miR-375 led to a significant increase in the protein expression levels of RUNX2. In addition, overexpression of RUNX2 was observed to attenuate the miR-375-mediated suppression of osteogenic differentiation. Therefore, the results demonstrated that miR-375 was able to inhibit osteogenic differentiation via the regulation of RUNX2 expression.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Feiya
authors.initials: F
authors.lastname: DU
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhiqin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Breast Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Y U
authors.initials: YU
authors.lastname: Liu
keywords: microRNA-375; osteoblast; osteogenic differentiation; runt-related transcription factor 2