title: PDGF-regulated miRNA-138 inhibits the osteogenic differentiation of mesenchymal stem cells.
abstract: Differentiation-specific microRNAs may play a critical role in MSC differentiation, and they can be altered by PDGF signaling. We propose that PDGF modulates MSC differentiation by regulating microRNA expression. Therefore, we investigated whether PDGF treatment could alter the expression profile of miRNAs in MSCs. Furthermore, we assessed the osteoblast phenotype of MSCs after inducing osteogenic differentiation. We found that PDGF treatment significantly inhibits the osteogenic differentiation of MSCs and that miR-138 gene transcription is controlled by PDGF signaling. Our results confirm that miR-138 inhibits the osteogenic differentiation of MSCs and suppresses the phosphorylation of FAK, ERK1/2, and Runx2. Furthermore, our study clearly demonstrates that downregulation of Runx2 by miR-138 is critical for the PDGF-mediated inhibition of osteogenic differentiation of MSCs. These findings indicate that inhibition of miR-138 function in MSCs, either by treatment with anti-miR-138 or by overexpression of the miR-138 target sequence (miRNA sponge), could represent a potential therapeutic strategy for the treatment of bone homeostasis disorders caused by activation of the PDGF pathway.
authors.affiliation: Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Qu
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Hong-hua
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address: tuchongqi2013@163.com.
authors.forename: Chong-qi
authors.initials: CQ
authors.lastname: Tu
authors.affiliation: Department of Orthopaedics, Chengdu Military General Hospital, Chengdu, Sichuan Province, China.
authors.forename: Xian-ming
authors.initials: XM
authors.lastname: Pan
mesh_terms: D000077214:Becaplermin; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D015536:Down-Regulation; D006706:Homeostasis; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics* / Q000502:physiology*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C546110:MIRN138 microRNA, human; D035683:MicroRNAs; D020574:Proto-Oncogene Proteins c-sis; C493709:RUNX2 protein, human; D011994:Recombinant Proteins; D000077214:Becaplermin
keywords: Osteogenic differentiation; Platelet-derived growth factor; microRNA-138