title: Effect of miR-26a-5p on the Wnt/Ca(2+) Pathway and Osteogenic Differentiation of Mouse Adipose-Derived Mesenchymal Stem Cells.
abstract: Elucidation of the molecular mechanisms that regulate the differentiation of adipose-derived mesenchymal stem cells into osteogenic cells may lead to new methods for bone tissue engineering. We examined the role of miR-26a-5p in the regulation of osteogenic differentiation of mouse adipose-derived mesenchymal stem cells (mADSCs) by using mimics and inhibitors of this microRNA. Our results showed that over-expression of miR-26a-5p inhibited osteogenesis and that suppression of endogenous miR-26a-5p promoted osteogenesis. Four bioinformatics algorithms indicated that the 3'UTR of Wnt5a was a potential target of miR-26a-5p. We confirmed this prediction by use of dual-luciferase reporter assay and GFP/RFP assay. We also examined the molecular mechanisms by which miR-26a-5p regulates osteogenesis. Fura-2AM and Western blot assays after transfection indicated that miR-26a-5p repressed WNT5A, inhibited calcium flux and protein kinase C, and suppressed osteogenic differentiation of mADSCs. By contrast, miR-26a-5p inhibition activated these signal proteins and promoted osteogenic differentiation. Taken together, our results suggest that up-regulation of miR-26a-5p inhibits osteogenic differentiation of mADSCs by directly targeting the 3'UTR of Wnt5a, thereby down-regulating the Wnt/Ca(2+) signaling pathway.
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Oral and Maxillofacial Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Oral and Maxillofacial Surgery, Binzhou Medical University Hospital, Binzhou, 256603, People's Republic of China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
authors.affiliation: The State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, 610041, People's Republic of China. dr.jielong@hotmail.com.|Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, 610041, People's Republic of China. dr.jielong@hotmail.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Long
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D050154:Adiposity / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics
chemical_list: D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D051153:Wnt Proteins; D002118:Calcium
keywords: Adipose-derived mesenchymal stem cell (ADSC); MicroRNA-26a-5p; Non-canonical Wnt pathway; Osteogenic differentiation; WNT5A