title: Small nuclear ribonucleoprotein polypeptide N (Sm51) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating Runx2.
abstract: Small nuclear ribonucleoprotein-associated polypeptide N mutation in mice is associated with short limbs and lower bone mineral density, yet the role of Sm51 in MSC differentiation to osteoblasts is not known. In the present study, we investigate the role of Sm51 in regulating osteoblastic differentiation of bone marrow-derived mesenchymal stem cells (BM-MSCs). Stable overexpression of Sm51 in rat and human BM-MSCs (Sm51-MSCs) significantly enhanced their osteogenic differentiation potential compared to untransfected cells. Under osteogenic induction, Sm51-MSCs had higher alkaline phosphatase (ALP) activity and mineralization ability; the expression of osteogenic genes such as runt-related transcription factor 2 (Runx2), osteocalcin, osteopontin, ALP and type I collagen was significantly upregulated compared to the control BM-MSCs. Furthermore, we show that Sm51 overexpression upregulated Runx2 expression at both the RNA and protein level; Sm51 could bind to Runx2 RNA and regulate its expression. Finally, knocking down Runx2 abolished the promoting effects of Sm51 on osteogenesis in BM-MSCs. These results demonstrate that Sm51 plays an important role in regulating osteogenic differentiation of MSCs through increasing Runx2 expression and that Sm51 may be a potential new therapeutic target for promoting bone formation.
authors.affiliation: Health Science Center, Shenzhen University, Shenzhen, China.|Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.
authors.forename: Fanbiao
authors.initials: F
authors.lastname: Meng
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
authors.forename: Kuixing
authors.initials: K
authors.lastname: Wang
authors.affiliation: Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. xjiang@cuhk.edu.hk.|MOE Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. xjiang@cuhk.edu.hk.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Room 904, 9/F, Shatin, Hong Kong, SAR, China. gangli@cuhk.edu.hk.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, China. gangli@cuhk.edu.hk.|Epithelial Cell Biology Research Center, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. gangli@cuhk.edu.hk.|MOE Key Laboratory for Regenerative Medicine, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China. gangli@cuhk.edu.hk.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D010012:Osteogenesis; D011485:Protein Binding; D012313:RNA / Q000378:metabolism; D051381:Rats; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism*; D055517:snRNP Core Proteins / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D050659:Core Binding Factor Alpha 1 Subunit; D017411:Ribonucleoproteins, Small Nuclear; C000618873:small nuclear ribonucleoprotein polypeptide N, rat; D055517:snRNP Core Proteins; D012313:RNA
keywords: Mesenchymal stem cells; Osteogenesis; Runx2; Sm51