RUNX2 mutation inhibits the cellular senescence of dental follicle cells via ERK signalling pathway. 2024

LingLi Ji, and Jie Li, and Dandan Liu, and Yanchun Qiao, and Weiwei Zhao, and Yang Liu, and Shuguo Zheng
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.

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. 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.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002973 Cleidocranial Dysplasia Autosomal dominant syndrome in which there is delayed closing of the CRANIAL FONTANELLES; complete or partial absence of the collarbones (CLAVICLES); wide PUBIC SYMPHYSIS; short middle phalanges of the fifth fingers; and dental and vertebral anomalies. Cleidocranial Dysostosis,Dysostosis, Cleidocranial,Cleidocranial Digital Dysostosis,Marie-Sainton Syndrome,Scheuthauer-Marie-Sainton Syndrome,Cleidocranial Digital Dysostoses,Cleidocranial Dysostoses,Cleidocranial Dysplasias,Dysostoses, Cleidocranial,Dysostoses, Cleidocranial Digital,Dysostosis, Cleidocranial Digital,Dysplasia, Cleidocranial,Dysplasias, Cleidocranial,Marie Sainton Syndrome,Scheuthauer Marie Sainton Syndrome,Syndrome, Marie-Sainton,Syndrome, Scheuthauer-Marie-Sainton
D003795 Dental Sac Dense fibrous layer formed from mesodermal tissue that surrounds the epithelial enamel organ. The cells eventually migrate to the external surface of the newly formed root dentin and give rise to the cementoblasts that deposit cementum on the developing root, fibroblasts of the developing periodontal ligament, and osteoblasts of the developing alveolar bone. Dental Follicle,Dental Follicles,Dental Sacs,Follicle, Dental,Follicles, Dental,Sac, Dental,Sacs, Dental
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D016022 Case-Control Studies Comparisons that start with the identification of persons with the disease or outcome of interest and a control (comparison, referent) group without the disease or outcome of interest. The relationship of an attribute is examined by comparing both groups with regard to the frequency or levels of outcome over time. Case-Base Studies,Case-Comparison Studies,Case-Referent Studies,Matched Case-Control Studies,Nested Case-Control Studies,Case Control Studies,Case-Compeer Studies,Case-Referrent Studies,Case Base Studies,Case Comparison Studies,Case Control Study,Case Referent Studies,Case Referrent Studies,Case-Comparison Study,Case-Control Studies, Matched,Case-Control Studies, Nested,Case-Control Study,Case-Control Study, Matched,Case-Control Study, Nested,Case-Referent Study,Case-Referrent Study,Matched Case Control Studies,Matched Case-Control Study,Nested Case Control Studies,Nested Case-Control Study,Studies, Case Control,Studies, Case-Base,Studies, Case-Comparison,Studies, Case-Compeer,Studies, Case-Control,Studies, Case-Referent,Studies, Case-Referrent,Studies, Matched Case-Control,Studies, Nested Case-Control,Study, Case Control,Study, Case-Comparison,Study, Case-Control,Study, Case-Referent,Study, Case-Referrent,Study, Matched Case-Control,Study, Nested Case-Control
D016922 Cellular Senescence Process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing CELL DEATH. Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS. Aging, Cell,Cell Aging,Cell Senescence,Replicative Senescence,Senescence, Cellular,Senescence, Replicative,Cell Ageing,Cellular Ageing,Cellular Aging,Ageing, Cell,Ageing, Cellular,Aging, Cellular,Senescence, Cell
D049109 Cell Proliferation All of the processes involved in increasing CELL NUMBER including CELL DIVISION. Cell Growth in Number,Cellular Proliferation,Cell Multiplication,Cell Number Growth,Growth, Cell Number,Multiplication, Cell,Number Growth, Cell,Proliferation, Cell,Proliferation, Cellular
D050659 Core Binding Factor Alpha 1 Subunit A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION. AML3 Transcription Factor,Acute Myeloid Leukemia 3 Protein,CBFA-1 Protein,CBFA1 Protein,CBFalpha Runt Domain Transcription Factor 1,CBFalpha1 Protein,Osf2 Transcription Factor,PEBP2alphaA Protein,Runx2 Protein,SEF1 Protein,SL3-3 Enhancer Factor 1,CBFA 1 Protein,SL3 3 Enhancer Factor 1
D020935 MAP Kinase Signaling System An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade. MAP Kinase Cascade,MAP Kinase Module,MAP Kinase Signaling Cascade,MAP Kinase Signaling Pathway,MAP Kinase Signaling Pathways,ERK Pathway,ERK Signal Tranduction Pathway,ERK1 and ERK2 Pathway,ERK1-2 Pathway,JNK Pathway,JNK Signaling Pathway,MAP Kinase Modules,MAP Kinase Signaling Cascades,MEK-ERK Pathway,p38 Kinase Pathway,p38 Kinase Signaling Pathway,Cascade, MAP Kinase,ERK Pathways,ERK1 2 Pathway,ERK1-2 Pathways,JNK Pathways,JNK Signaling Pathways,Kinase Cascade, MAP,Kinase Pathway, p38,Kinase Pathways, p38,MAP Kinase Cascades,MEK ERK Pathway,MEK-ERK Pathways,Module, MAP Kinase,Pathway, ERK,Pathway, ERK1-2,Pathway, JNK,Pathway, JNK Signaling,Pathway, MEK-ERK,Pathway, p38 Kinase,Pathways, ERK,Pathways, ERK1-2,Pathways, JNK,Pathways, JNK Signaling,Pathways, MEK-ERK,Pathways, p38 Kinase,Signaling Pathway, JNK,Signaling Pathways, JNK,p38 Kinase Pathways

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