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Published on: May 4, 2018
MicroRNA-503-5p inhibits stretch-induced osteogenic differentiation and bone formation
Lu Liu1, Mengjun Liu1, Rongrong Li1
1Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
Abstract:
Cyclical stretch-induced bone formation during orthodontic treatment is a complex biological process modulated by various factors including miRNAs and their targeted-gene network. However, the miRNA expression profile and their roles in osteogenic differentiation of bone mesenchymal stem cells (BMSCs) exposed to mechanical stretch remains unclear. Here, we use the miRNA microarray assay to screen for mechano-sensitive miRNAs during stretch-induced osteogenic differentiation of BMSCs and identified that nine miRNAs were differentially expressed between stretched and control BMSCs. Furthermore, miR-503-5p, which was markedly downregulated in both microarray assay and qRT-PCR assay were selected for further functional verification. We found that overexpression of miR-503-5p in BMSCs attenuated stretch-induced osteogenic differentiation while the effect was reversed by miR-503-5p inhibition treatment. In vivo studies, overexpression of miR-503-5p with specific agomir decreased Runx2, ALP mRNA, and protein expression, decreased osteoblast numbers and osteoblastic bone formation in the OTM tension sides. In conclusion, our study revealed that miR-503-5p functions as the mechano-sensitive miRNA and inhibits BMSCs osteogenic differentiation subjected to mechanical stretch and bone formation in OTM tension sides.
Insights
MicroRNAs regulate bone formation during orthodontic tooth movement. This study found miR-503-5p inhibits osteogenic differentiation of bone mesenchymal stem cells (BMSCs) under mechanical stretch, impacting bone formation.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Orthodontics
Background:
- Orthodontic treatment relies on bone remodeling.
- MicroRNAs (miRNAs) are key regulators of gene expression.
- The role of miRNAs in mechanotransduction during bone formation is not fully understood.
Purpose of the Study:
- To identify mechano-sensitive miRNAs in bone mesenchymal stem cells (BMSCs) under cyclical stretch.
- To investigate the function of miR-503-5p in regulating osteogenic differentiation and bone formation during orthodontic tooth movement (OTM).
Main Methods:
- miRNA microarray assay to screen for differentially expressed miRNAs.
- Quantitative real-time PCR (qRT-PCR) for miRNA validation.
- In vitro cell culture of BMSCs subjected to mechanical stretch.
- In vivo studies using agomir to modulate miR-503-5p expression in a mouse OTM model.
Main Results:
- Nine miRNAs were identified as mechano-sensitive.
- miR-503-5p was significantly downregulated in stretched BMSCs.
- Overexpression of miR-503-5p inhibited stretch-induced osteogenic differentiation in vitro.
- In vivo, miR-503-5p inhibition promoted osteoblast activity and bone formation in the OTM tension side.
Conclusions:
- miR-503-5p acts as a mechano-sensitive miRNA that inhibits osteogenic differentiation of BMSCs.
- miR-503-5p plays a crucial role in regulating bone formation during orthodontic tooth movement.
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