Small nuclear ribonucleoprotein polypeptide N (Sm51) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating Runx2
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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.
KeywordMesenchymal stem cells Osteogenesis Sm51 Runx2
The work was partially supported by grants from the National Natural Science Foundation of China (NSFC No.81371946, 81272548, 81374568, 31400834) to Gang Li, Xiao-hua Jiang and Liangliang Xu respectively. Hong Kong Government Research Grant Council, General Research Fund (CUHK470813 and 14119115) and a project grant from China Shenzhen City Science and Technology Bureau (JGJHZ20140419120051680) to Gang Li are gratefully acknowledged. This study was also supported in part by the SMART program, the Lui Che Woo Institute of Innovative Medicine and The Chinese University of Hong Kong. The research was made possible by resources donated by the Lui Che Woo Foundation Limited.
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Author disclosure statement
The authors declare that they have no competing or conflicting interests.
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