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IFT80 is required for stem cell proliferation, differentiation, and odontoblast polarization during tooth development

机译:牙齿发育期间,干细胞增殖,分化和成牙本质细胞极化需要IFT80

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摘要

Primary cilia and intraflagellar transport (IFT) proteins control a wide variety of processes during tissue development and homeostasis. However, their role in regulation of stem cell properties during tooth development remains elusive. Here, we revealed that dental pulp stem cells (DPSCs) express IFT80, which is required for maintaining DPSC properties. Mice with deletion of IFT80 in odontoblast lineage show impaired molar root development and delayed incisor eruption through reduced DPSC proliferation and differentiation, and disrupted odontoblast polarization. Impaired odontoblast differentiation resulted from disrupted hedgehog (Hh) signaling pathways. Decreased DPSC proliferation is associated with impaired fibroblast growth factor 2 (FGF2) signaling caused by loss of IFT80, leading to the disruption of FGF2-FGFR1-PI3K-AKT signaling in IFT80-deficient DPSCs. The results provide the first evidence that IFT80 controls tooth development through influencing cell proliferation, differentiation, and polarization, and Hh and FGF/AKT signaling pathways, demonstrating that IFT proteins are likely to be the new therapeutic targets for tooth and other tissue repair and regeneration.
机译:初级纤毛和鞭毛内运输(IFT)蛋白控制组织发育和体内平衡过程中的多种过程。但是,它们在牙齿发育过程中对干细胞特性的调节作用仍然难以捉摸。在这里,我们揭示了牙髓干细胞(DPSC)表达IFT80,这是维持DPSC特性所必需的。在成牙本质细胞系中缺失IFT80的小鼠表现出磨牙根发育受损,并通过减少DPSC增殖和分化而破坏了切牙萌发,并破坏了成牙本质细胞极化。成牙本质细胞分化受损是由于刺猬(Hh)信号传导途径中断所致。 DPSC增殖减少与IFT80缺失引起的成纤维细胞生长因子2(FGF2)信号转导受损有关,导致IFT80缺失的DPSC中FGF2-FGFR1-PI3K-AKT信号转导受到破坏。结果提供了第一个证据,即IFT80通过影响细胞增殖,分化和极化以及Hh和FGF / AKT信号传导通路来控制牙齿的发育,表明IFT蛋白很可能是牙齿和其他组织修复和再生的新治疗靶标。 。

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