Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells
Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells
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Sonic Hedgehog 增强骨髓间充质干细胞的增殖和成骨分化
DOI：
10.1042/cbi20110284
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发表时间：
2012-04-01
影响因子：
3.9
通讯作者：
Deng, Li
中科院分区：
文献类型：
--
作者：
Cai, Jia-Qin;Huang, Yi-Zhou;Deng, Li
间充质干细胞（MSCs）具有自我更新和多向分化的潜能，是一种很有前途的组织再生种子细胞。Shh （sonic hedgehog）参与胚胎发育和骨骼再生过程中的骨骼形成。然而，Shh如何调节骨髓间充质干细胞（bmmscs）的生物学特性尚不清楚。我们在体外研究了重组n端Shh对rBM-MSCs（大鼠BM-MSCs）增殖和成骨分化的影响。rsh - n浓度高达200 ng/ml处理rBM-MSCs。rBM-MSCs的增殖和集落形成能力呈剂量依赖性增加。rsh - n增加了S期和G(2)/M期细胞比例，增加了Ki-67（+）细胞数量。此外，200 ng/ml rsh - n可增强碱性磷酸酶活性和基质矿化。Real-time PCR结果显示，rsh - n （200 ng/ml）上调rBM-MSCs中Cbfa-1（核心结合因子α 1）、骨钙素、ALP和I型胶原编码基因的表达。这一信息揭示了rsh - n在骨相关疾病治疗中的一些潜力。
MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration because of their self-renewal and multi-differentiation potential. Shh (sonic hedgehog) is involved in the skeletal formation during embryo development and skeletal regeneration. However, how Shh regulates the biological characteristics of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony-forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N increased the ratio of cells in S and G(2)/M phase, as well as the number of Ki-67(+) cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml) up-regulated the expression of genes encoding Cbfa-1 (core-binding factor alpha 1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information reveals some potential of rShh-N in the therapeutics of bone-related diseases.