title: MicroRNA signature associated with osteogenic lineage commitment.
abstract: Cell-based approaches offer a potential therapeutic strategy for appropriate bone manufacturing. Capable of differentiating into multiple cell types especially osteoblasts spontaneously, unrestricted somatic stem cell (USSC) seems to be a suitable candidate. Recent studies have shown the involvement of microRNAs in several biological processes. miRNA microarray profiling was applied in order to identify the osteo-specific miRNA signature. Prior to this analysis, osteogenic commitment of osteoblasts was evaluated by measuring ALPase activity, biomineralization, specific staining and evaluation of some main osteogenic marker genes. To support our findings, various in silico explorations (for both putative targets and signaling pathways) and empirical analyses (miRNA transfections followed by qPCR of osteogenic indicators and ALPase activity measurement) were carried out. The function of GSK-3b inhibitor was also studied to investigate the role of WNT in osteogenesis. Transient modulation of multiple osteo-miRs (such as mir-199b, 1274a, 30b) with common targets (such as BMPR, TCFs, SMADs) as mediators of osteogenic pathways including cell-cell interactions, WNT and TGF-beta pathways, suggests a mechanism for rapid induction of the osteogenesis as an anti-miRNA therapy. The results of this research have identified the miRNA signature which regulates the osteogenesis mechanism in USSC. To conclude, our study reveals more details about the allocation of USSCs into osteogenic lineage through modulatory effect of miRNAs on targets and pathways required for creating a tissue-specific phenotype and may aid in future clinical interventions.
authors.affiliation: Department of Biotechnology, College of Science, University of Tehran, Tehran, Iran.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Bakhshandeh
authors.forename: Masoud
authors.initials: M
authors.lastname: Soleimani
authors.forename: Maryam
authors.initials: M
authors.lastname: Hafizi
authors.forename: Seyed Hassan
authors.initials: SH
authors.lastname: Paylakhi
authors.forename: Nasser
authors.initials: N
authors.lastname: Ghaemi
mesh_terms: D016723:Bone Remodeling / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage; D049109:Cell Proliferation; D002478:Cells, Cultured; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3