Dataset Information

MiR-20a: a mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6.

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

In the present study, we subjected osteoblast MC3T3-E1 cells or mouse bone marrow stromal cells (BMSCs) to single bout short duration FSS (12 dyn/cm² 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.

SUBMITTER: Peng Z

PROVIDER: S-EPMC9279817 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

MiR-20a: a mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6.

Peng Zhuli Z Mai Zhihui Z Xiao Feng F Liu Guanqi G Wang Yixuan Y Xie Shanshan S Ai Hong H

Annals of translational medicine 20220601 12

<h4>Background</h4>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.<h4>Methods</h4>In the present study, we subjected osteoblast MC3T3-E1 cells or mouse bone marrow stromal cells (BMSCs) to single bout short duration FSS (12 dyn/cm<sup>2</sup> for 1 hour) using a parallel plate flow system. The expression of miR-20a was qua ...[more]

PMID: 35845505

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Project description:Osteoporosis is a common bone and metabolic disease that is characterized by bone density loss and microstructural degeneration. Human bone marrow-derived mesenchymal stem cells (hMSCs) are multipotent progenitor cells with the potential to differentiate into various cell types, including osteoblasts, chondrocytes, and adipocytes, which have been utilized extensively in the field of bone tissue engineering and cell-based therapy. Although fluid shear stress plays an important role in bone osteogenic differentiation, the cellular and molecular mechanisms underlying this effect remain poorly understood. Here, a locked nucleic acid (LNA)/DNA nanobiosensor was exploited to monitor mRNA gene expression of hMSCs that were exposed to physiologically relevant fluid shear stress to examine the regulatory role of Notch signaling during osteogenic differentiation. First, the effects of fluid shear stress on cell viability, proliferation, morphology, and osteogenic differentiation were investigated and compared. Our results showed shear stress modulates hMSCs morphology and osteogenic differentiation depending on the applied shear and duration. By incorporating this LNA/DNA nanobiosensor and alkaline phosphatase (ALP) staining, we further investigated the role of Notch signaling in regulating osteogenic differentiation. Pharmacological treatment is applied to disrupt Notch signaling to investigate the mechanisms that govern shear stress induced osteogenic differentiation. Our experimental results provide convincing evidence supporting that physiologically relevant shear stress regulates osteogenic differentiation through Notch signaling. Inhibition of Notch signaling mediates the effects of shear stress on osteogenic differentiation, with reduced ALP enzyme activity and decreased Dll4 mRNA expression. In conclusion, our results will add new information concerning osteogenic differentiation of hMSCs under shear stress and the regulatory role of Notch signaling. Further studies may elucidate the mechanisms underlying the mechanosensitive role of Notch signaling in stem cell differentiation.

Dataset Information

MiR-20a: a mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6.

Background

Methods

Results

Conclusions

Publications

MiR-20a: a mechanosensitive microRNA that regulates fluid shear stress-mediated osteogenic differentiation via the BMP2 signaling pathway by targeting BAMBI and SMAD6.

Similar Datasets

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