title: MicroRNA-503-5p inhibits stretch-induced osteogenic differentiation and bone formation.
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.
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Mengjun
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Liling
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, School of Dentistry, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Orthodontics, Shandong Provincial Key Laboratory of Oral Biomedicine, School of Dentistry, Shandong University, Jinan, 250012, China.
authors.forename: Dongxu
authors.initials: D
authors.lastname: Liu
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005269:Femur / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D023421:Models, Animal; D010012:Osteogenesis / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D013314:Stress, Mechanical; D013977:Tibia / Q000166:cytology; D014087:Tooth Movement Techniques; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000070416:Antagomirs; D050659:Core Binding Factor Alpha 1 Subunit; D035683:MicroRNAs; C493717:Runx2 protein, rat; C495181:Sp7 protein, rat; D014157:Transcription Factors; D000469:Alkaline Phosphatase
keywords: BMSCs; MiR-503-5p; bone formation; mechanical stretch; osteogenic differentiation