Ji LingLi, Li Jie, Liu Dandan, Qiao Yanchun, Zhao Weiwei, Liu Yang, Zheng Shuguo
Department of Preventive Dentistry, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, PR China.
Oral Dis. 2024 Apr;30(3):1337-1349. doi: 10.1111/odi.14607. Epub 2023 May 8.
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.
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.
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.
RUNX2 mutation delayed DFCs senescence through the ERK signalling pathway, which may be responsible for delayed permanent tooth eruption in CCD patients.
本研究旨在探讨RUNX2突变对牙囊细胞（DFCs）衰老的调控作用，并阐明其潜在机制。本研究旨在探寻锁骨颅骨发育不全（CCD）患者恒牙萌出延迟新机制的依据。
从一名CCD患者和健康对照者处收集牙囊。进行衰老相关β-半乳糖苷酶（SA-β-gal）染色、Ki67染色、细胞周期分析以及衰老相关基因和蛋白表达分析，以评估DFCs衰老情况。采用蛋白质印迹法检测丝裂原活化蛋白激酶（MAPK）信号通路的激活情况，探讨RUNX2调控DFCs衰老的分子机制。
与健康对照相比，RUNX2突变抑制了CCD患者DFCs的细胞衰老。Ki67染色显示突变型RUNX2促进DFCs增殖，细胞周期分析表明健康对照来源的DFCs停滞于G1期。RUNX2突变显著下调衰老相关基因和蛋白的表达。RUNX2突变抑制ERK信号通路激活，ERK抑制剂可降低健康对照来源的DFCs衰老，而ERK激活剂可促进CCD患者来源的DFCs衰老。
RUNX2突变通过ERK信号通路延迟DFCs衰老，这可能是CCD患者恒牙萌出延迟的原因。
