背景:Hedgehog信号通路不仅参与骨髓间充质干细胞的成骨向分化,而且是位于RANKL-RANK-OPG系统调节轴上游的重要通路之一,对成骨细胞RANKL的分泌表达具有重要的调控作用,其调控机制已逐步被揭示。目的:对Hedgehog信号通路调控成骨细胞RANKL表达的研究现状进行综述。方法:通过检索CNKI,Google Scholar,PubM ed等数据库,分别以"Hedgehog,成骨细胞,骨髓间充质干细胞,甲状旁腺激素相关蛋白,环磷酸腺苷应答元件结合蛋白,活化T细胞核因子,核因子κB受体活化因子配体"和"Hedgehog,Osteoblast,BMSCs,PTHrP,CREB,NFAT,RANKL"为检索词进行检索,审阅有关Hedgehog信号通路与成骨细胞RANKL表达相关的文献,根据纳入标准最终选取37篇文献进行综述。结果与结论:Hedgehog信号蛋白可促使骨髓间充质干细胞向成骨细胞分化,同时又可以通过上调细胞内甲状旁腺激素相关蛋白的表达,进一步激活下游细胞因子环磷酸腺苷应答元件结合蛋白和活化T细胞核因子,两者协同促使成骨细胞RANKL基因表达,进而增加破骨前体细胞向破骨细胞分化、成熟。
BACKGROUND: Hedgehog signaling pathway is shown to contribute to the osteogenesis of bone marrow mesenchymal stem cells, and to play an important role in regulating the expression of RANKL in osteoblasts. Nowadays, the definite signal transduction pathway has been revealed gradually.OBJECTIVE: To review the research progress of RANKL in osteoblasts that regulated by hedgehog signaling pathway.METHODS: A computer-based online search in CNKI, Google Scholar and PubMed databases was performed with the key words of "Hedgehog, osteoblast, BMSCs, PTHrP, CREB, NFAT, RANKL" in English and Chinese, respectively.Literatures related to the expression of RANKL in osteoblasts that regulated by the Hedgehog signaling pathway were included initially and 37 eligible articles were extensively summarized for review.RESULTS AND CONCLUSION: The Hedgehog signaling pathway plays an advanced role in the osteogenic differentiation of bone marrow mesenchymal stem cells, and also upregulates intracellular parathyroid hormone related protein, which activates its downstream signaling molecules cAMP response element binding protein and nuclear factor of activated T cells ulteriorly, to promote the expression of RANKL in osteoblasts and increase the differentiation and formation from osteoclast precursor cells to mature osteoclasts.