Small nuclear ribonucleoprotein polypeptide N (Sm51) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating Runx2
Small nuclear ribonucleoprotein polypeptide N (Sm51) promotes osteogenic differentiation of bone marrow mesenchymal stem cells by regulating Runx2
复制标题
小核核糖核蛋白多肽N（Sm51）通过调控Runx2促进骨髓间充质干细胞成骨分化
DOI：
10.1007/s00441-016-2411-0
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发表时间：
2016-10-01
影响因子：
3.6
通讯作者：
Li, Gang
中科院分区：
文献类型：
--
作者：
Meng, Fanbiao;Xu, Liangliang;Li, Gang
小鼠小核核糖核蛋白相关多肽N突变与短肢和低骨密度相关，但Sm 51在MSC分化为成骨细胞中的作用尚不清楚。在本研究中，我们研究Sm 51在调节骨髓间充质干细胞（BM-MSCs）的成骨分化中的作用。Sm 51在大鼠和人BM-MSCs中的稳定过表达（Sm 51-MSCs）与未转染的细胞相比显著增强了它们的成骨分化潜能。在成骨诱导下，Sm 51-MSCs具有更高的碱性磷酸酶（ALP）活性和矿化能力;与对照BM-MSCs相比，成骨相关基因Runx 2、骨钙素、骨桥蛋白、ALP和I型胶原的表达显著上调。此外，我们发现Sm 51过表达上调Runx 2的表达在RNA和蛋白质水平; Sm 51可以结合Runx 2 RNA和调节其表达。最后，敲除Runx 2可取消Sm 51对BM-MSCs成骨的促进作用。这些结果表明Sm 51通过增加Runx 2表达在调节MSC的成骨分化中起重要作用，并且Sm 51可能是促进骨形成的潜在新治疗靶点。
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.