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[刺猬信号通路调控骨间充质干细胞骨形成及成骨分化的研究进展]

[RESEARCH PROGRESS OF Hedgehog SIGNALING PATHWAY IN REGULATING BONE FORMATION AND OSTEOGENIC DIFFERENTIATION OF BONE MESENCHYMAL STEM CELLS].

作者信息

Chi Bojing, Liu Guangyuan, Xing Lei, Tian Faming

机构信息

Graduate School, North China University of Science and Technology, Tangshan Hebei, 063000, P. R. China.

Hebei Medical University, Tangshan Hebei, 063000, P. R. China.

出版信息

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2016 Dec 8;30(12):1545-1550. doi: 10.7507/1002-1892.20160318.

Abstract

OBJECTIVE

To summarize the research progress of the effects and mechanisms of Hedgehog signaling pathway in regulating bone formation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).

METHODS

The related literature concerning the regulations and mechanism of Hedgehog signaling pathway in osteogenic differentiation of BMSCs and bone formation , , and studies in recent years was analyzed and summarized.

RESULTS

The studies indicate that Hedgehog signaling pathway can promote osteogenic differentiation of BMSCs via activation of key molecules Smoothened (Smo) and Gli1 which are downstream of Hedgehog signaling, and Hedgehog signaling can activate mTORC2-Akt signaling by upregulation of insulin-like growth factor which has similar effects. Hedgehog signaling regulates osteoblast differentiation via activation of Hh-Smo-Ptch1-Gli signaling pathway and inhibition of Hh-Gαi-RhoA stress fibre signaling. Hedgehog signaling can regulate key molecules of osteogenesis Runx2 for promoting osteogenic differentiation and matrix mineralization by synergism of bone morphogenetic protein and Wnt signaling, and promotes bone formation and repair and healing for bone defect and bone graft model .

CONCLUSIONS

Hedgehog signaling can regulate bone formation and osteogenic differentiation of BMSCs via activation of Hedgehog signaling and other signaling pathways. Hedgehog signaling pathway may be a potential target for developing treatment for bone related diseases of osteoporosis and fracture healing disorders.

摘要

目的

总结刺猬信号通路在调节骨髓间充质干细胞(BMSCs)成骨分化及骨形成中的作用及机制的研究进展。

方法

分析和总结近年来有关刺猬信号通路在BMSCs成骨分化及骨形成中的调控作用及机制的相关文献。

结果

相关研究表明,刺猬信号通路可通过激活刺猬信号下游关键分子Smoothened(Smo)和Gli1促进BMSCs成骨分化,且刺猬信号可通过上调具有相似作用的胰岛素样生长因子激活mTORC2-Akt信号。刺猬信号通过激活Hh-Smo-Ptch1-Gli信号通路及抑制Hh-Gαi-RhoA应激纤维信号调节成骨细胞分化。刺猬信号可通过骨形态发生蛋白和Wnt信号协同作用调节成骨关键分子Runx2,促进成骨分化和基质矿化,并在骨缺损和骨移植模型中促进骨形成及修复愈合。

结论

刺猬信号可通过激活刺猬信号及其他信号通路调节BMSCs的骨形成及成骨分化。刺猬信号通路可能是开发骨质疏松症及骨折愈合障碍等骨相关疾病治疗方法的潜在靶点。

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