MiR-20a: a mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6
Zhuli Peng, Zhihui Mai, Feng Xiao, Guanqi Liu, Yixuan Wang, Shanshan Xie, Hong Ai
Abstract
Background: MicroRNAs (miRNAs) are crucial regulators of diverse biological and pathological processes. This study aimed to investigate the role of microRNA 20a (miR-20a) in fluid shear stress (FSS)-mediated osteogenic differentiation. Methods: for 1 hour) using a parallel plate flow system. The expression of miR-20a was quantified by miRNA array profiling and real-time quantitative polymerase chain reaction (qRT-PCR) during FSS-mediated osteogenic differentiation. The expression of osteogenic differentiation markers such as Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), and SP7 transcription factor (SP7) was detected. Bioinformatics analysis and a luciferase assay were performed to confirm the potential targets of miR-20a. Results: Osteoblast-expressed miR-20a is sensitive to the mechanical environments of FSS, which are differentially up-regulated during steady FSS-mediated osteogenic differentiation. MiR-20a enhances FSS-induced osteoblast differentiation by activating the bone morphogenetic protein 2 (BMP2) signaling pathway. Both BMP and activin membrane-bound inhibitor (BAMBI) and mothers against decapentaplegic family member 6 (SMAD6) are targets of miR-20a that negatively regulate the BMP2 signaling pathway. Conclusions: MiR-20a is a novel mechanosensitive miRNA that can enhance osteoblast differentiation in FSS mechanical environments, implying that this miRNA might be a target for bone tissue engineering and orthodontic bone remodeling for regenerative medicine applications.