Cell Culture Laboratory, School of Dentistry of Ribeirao Preto, University of Sao Paulo, 14040-904 Ribeirao Preto, Sao Paulo, Brazil.
J Cell Biochem. 2012 Jan;113(1):204-8. doi: 10.1002/jcb.23345.
Several biological events are controlled by Hedgehog (Hh) signaling, including osteoblast phenotype development. This study aimed at evaluating the gene expression profile of human mesenchymal stem cells (hMSCs) treated with the Hh agonist, purmorphamine, focusing on Hh signaling and osteoblast differentiation. hMSCs from bone marrow were cultured in non-osteogenic medium with or without purmorphamine (2 µM) for periods of up to 14 days. Purmorphamine up-regulated gene expression of the mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. The activation of Hh pathway by purmorphamine increased the expression of several genes (e.g., RUNX2 and BMPs) related to osteogenesis. Our results indicated that purmorphamine triggers Hh signaling pathway in hMSCs, inducing an increase in the expression of a set of genes involved in the osteoblast differentiation program. Thus, we conclude that Hh is a crucial pathway in the commitment of undifferentiated cells to the osteoblast lineage.
几种生物事件受 Hedgehog（Hh）信号的控制，包括成骨细胞表型的发育。本研究旨在评估用 Hh 激动剂 purmorphamine 处理的人骨髓间充质干细胞（hMSC）的基因表达谱，重点关注 Hh 信号和成骨细胞分化。hMSC 取自骨髓，在非成骨培养基中培养，有或没有 purmorphamine（2μM），培养时间长达 14 天。Purmorphamine 上调了 Hh 通路的介质 SMO、PTCH1、GLI1 和 GLI2 的基因表达。Purmorphamine 激活 Hh 通路增加了与成骨相关的几个基因（如 RUNX2 和 BMPs）的表达。我们的结果表明，purmorphamine 触发了 hMSC 中的 Hh 信号通路，诱导一组参与成骨细胞分化程序的基因表达增加。因此，我们得出结论，Hh 是未分化细胞向成骨细胞谱系分化的关键途径。
