RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway.
RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway.
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DOI：
10.1111/odi.14607
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发表时间：
2023-05
期刊：
影响因子：
3.8
通讯作者：
Lingli Ji;Jiejin Li;Dandan Liu;Yanchun Qiao;Weiwei Zhao;Yang Liu;S. Zheng
中科院分区：
文献类型：
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作者：
Lingli Ji;Jiejin Li;Dandan Liu;Yanchun Qiao;Weiwei Zhao;Yang Liu;S. Zheng
目的探讨RUNX 2基因突变对牙囊细胞衰老的调控作用及其机制。本研究旨在探讨锁骨颅骨发育不良（CCD）患者恒牙延迟萌出的新机制。材料与方法收集CCD患者和健康对照者的牙囊。进行衰老相关β-半乳糖苷酶（SA-β-gal）染色、Ki 67染色、细胞周期测定以及衰老相关基因和蛋白表达测定以评估DFC衰老。Western blotting检测丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路的激活情况，探讨RUNX 2调控DFCs衰老的分子机制。结果RUNX 2基因突变抑制了CCD患者DFC细胞的衰老。Ki 67染色显示突变体RUNX 2促进DFCs增殖，细胞周期分析显示健康对照来源的DFCs阻滞于G1期。RUNX 2突变显著下调衰老相关基因和蛋白的表达。RUNX 2突变抑制ERK信号通路激活，ERK抑制剂降低健康对照来源的DFC衰老，ERK激活剂促进CCD患者来源的DFC衰老。结论RUNX 2基因突变通过ERK信号通路延缓牙胚成纤维细胞的衰老，可能是CCD患者恒牙萌出延迟的原因之一。
OBJECTIVE The aim of this study was to explore the regulatory effect of RUNX2 mutation on dental follicle cells (DFCs) senescence and clarify the underlying mechanism. This study aimed to explore the basis for a novel mechanism of delayed permanent tooth eruption in cleidocranial dysplasia (CCD) patients. MATERIALS AND METHODS Dental follicles were collected from a CCD patient and healthy controls. Senescence-associated β-galactosidase (SA-β-gal) staining, Ki67 staining, cell cycle assays, and senescence-related gene and protein expression assays were performed to assess DFCs senescence. Western blotting was performed to detect the activation of mitogen-activated protein kinase (MAPK) signalling pathways, and the molecular mechanism underlying RUNX2 regulating in DFCs senescence was explored. RESULTS RUNX2 mutation inhibited the cellular senescence of DFCs from the CCD patient compared with healthy controls. Ki67 staining showed that mutant RUNX2 promoted DFCs proliferation, and cell cycle assays revealed that the healthy control-derived DFCs arrested at G1 phase. RUNX2 mutation significantly downregulated senescence-associated gene and protein expression. RUNX2 mutation suppressed ERK signalling pathway activation, an ERK inhibitor decreased healthy control-derived DFCs senescence, and an ERK activator promoted CCD patient-derived DFCs senescence. CONCLUSIONS RUNX2 mutation delayed DFCs senescence through the ERK signalling pathway, which may be responsible for delayed permanent tooth eruption in CCD patients.