title: MicroRNAs-141 and 200a regulate the SVCT2 transporter in bone marrow stromal cells.
abstract: Vitamin C is a micro-nutrient which plays an important role in bone marrow stromal cell (BMSCs) differentiation to osteogenesis. This vitamin is transported into the BMSCs through the sodium dependent vitamin C transporter 2 (SVCT2). We previously reported that knockdown of the SVCT2 transporter decreases osteogenic differentiation. However, our understanding of the post-transcriptional regulatory mechanism of the SVCT2 transporter remains poor. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate the messenger RNAs of protein-coding genes. In this study, we aimed to investigate the impact of miR-141 and miR-200a on SVCT2 expression. We found that mouse BMSCs expressed miR-141 and miR-200a and repressed SVCT2 expression at the functional level by targeting the 3'-untranslated region of mRNA. We also found that miR-141 and miR-200a decreased osteogenic differentiation. Furthermore, miRNA inhibitors increased SVCT2 and osteogenic gene expression in BMSCs. Taken together, these results indicate that both miRNAs are novel regulators of the SVCT2 transporter and play an important role in the osteogenic differentiation of BMSCs.
authors.affiliation: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Rajnikumar
authors.initials: R
authors.lastname: Sangani
authors.affiliation: Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Sudharsan
authors.initials: S
authors.lastname: Periyasamy-Thandavan
authors.affiliation: Department of Pathology, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kolhe
authors.affiliation: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, USA; Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Maryka H
authors.initials: MH
authors.lastname: Bhattacharyya
authors.affiliation: The CORE Institute, Phoenix, AZ 85023, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Chutkan
authors.affiliation: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Monte
authors.initials: M
authors.lastname: Hunter
authors.affiliation: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, USA; Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Isales
authors.affiliation: Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA; Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hamrick
authors.affiliation: Cellular Biology and Anatomy, Georgia Regents University, Augusta, GA 30912, USA; Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA 30904, USA.
authors.forename: William D
authors.initials: WD
authors.lastname: Hill
authors.affiliation: Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA 30912, USA; Institute of Regenerative and Reparative Medicine, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: sfulzele@gru.edu.
authors.forename: Sadanand
authors.initials: S
authors.lastname: Fulzele
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C543718:Mirn141 microRNA, mouse; C543719:Mirn200 microRNA, mouse; C555165:Slc23a2 protein, mouse; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid
keywords: BMSCs; Osteogenic differentiation; SVCT2; Vitamin C transporter; miRNA-141; miRNA-200a