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Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells

机译:声波刺猬可促进骨髓间充质干细胞的增殖和成骨分化

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摘要

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 α 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.
机译:MSC(间充质干细胞)可能具有组织再生的潜力,因为它们具有自我更新和多重分化的潜能。 Shh(音速刺猬)参与胚胎发育和骨骼再生过程中的骨骼形成。然而,人们对Shh如何调节BM-MSC(骨髓源性MSC)的生物学特性了解甚少。我们已经研究了rShh-N(重组N末端Shh)对rBM-MSC(大鼠BM-MSC)的增殖和成骨分化的影响。用浓度达200 ng / ml的rShh-N处理rBM-MSC。 rBM-MSCs的增殖和集落形成能力以剂量依赖性方式增加。 rShh-N增加了S和G 2 / M期细胞的比例,以及Ki-67 +细胞的数量。另外,200 ng / ml rShh-N增强了ALP(碱性磷酸酶)的活性和基质矿化作用。实时PCR显示,rShh-N(200 ng / ml)上调了rBM-MSCs中编码Cbfa-1(核心结合因子α1),骨钙素,ALP和I型胶原的基因的表达。该信息揭示了rShh-N在骨相关疾病治疗中的潜力。

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