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首页> 外文期刊>Journal of Cellular Physiology >GSK3β regulates ameloblast differentiation via Wnt and TGF‐β pathways
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GSK3β regulates ameloblast differentiation via Wnt and TGF‐β pathways

机译：通过Wnt GSK3β调节造釉细胞分化然后TGFβ通路

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摘要

Wnt and TGF‐β signaling pathways participate in regulating a variety of cell fates during organogenesis, including tooth development. Despite well‐documented, the specific mechanisms, especially how these two pathways act coordinately in regulating enamel development, remain unknown. In this study, we identified Glycogen Synthase Kinase 3 beta (GSK3β), a negative regulator of Wnt signal pathway, participated in ameloblast differentiation via Wnt and TGF‐β pathways during enamel development. In vitro rat mandible culture treated with specific GSK3β inhibitor SB415286 displayed enamel defects, accompanied by disrupted ameloblasts polarization, while odontoblasts and dentin appeared to be unaffected. Moreover, after GSK3β knockdown by lentivirus‐mediated RNA silencing, HAT‐7 cells displayed abnormal cell polarity and cell adhesion, and failed to synthesize appreciable amounts of ameloblast‐specific proteins. More importantly, inactivation of GSK3β caused upregulated Wnt and downregulated TGF‐β pathway, while reactivation of TGF‐β signaling or suppression of Wnt signaling partially rescued the differentiation defects of ameloblasts caused by the GSK3β knock‐down. Taken together, these results suggested that GSK3β was essential for ameloblasts differentiation, which might be indirectly mediated through Wnt and TGF‐β signaling pathways.
机译：Wnt和TGFβ信号通路参与调节多种细胞的命运器官形成,包括牙齿发育。尽管作业记录,具体的机制,尤其是这两个通路如何行动协调在调节搪瓷发展,仍然未知。糖原合成酶激酶3β(GSK3β)Wnt信号通路的负面调节器,通过参与造釉细胞分化在搪瓷发展Wnt和TGFβ通路。体外大鼠下颌骨文化接受具体GSK3β抑制剂SB415286显示搪瓷缺陷,伴随着中断造釉细胞极化,而成牙质似乎未受影响。GSK3β击倒,慢病毒介导的RNA沉默,帽子还是7细胞显示不正常的细胞极性和细胞粘附和失败合成数额可观的造釉细胞特定的蛋白质。失活的GSK3β调节Wnt和引起的地理表达下调TGFβ通路,而复活TGFβ信号或抑制Wnt应承担的信号部分救了分化GSK3缺陷引起的造釉细胞β敲下来。建议GSK3β是必不可少的造釉细胞分化,这可能是间接介导通过Wnt和TGFβ信号通路。

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