title: RUNX2 mutation impairs bone remodelling of dental follicle cells and periodontal ligament cells in patients with cleidocranial dysplasia.
abstract: RUNX2 is an important osteo-specific factor with crucial functions in bone formation and remodelling as well as resorption of teeth. Heterozygous mutation of RUNX2 can cause cleidocranial dysplasia (CCD), a systemic disease with extensive skeletal dysplasia and abnormality of tooth growth. In our study, dental follicle cells (DFCs) and periodontal ligament cells (PDLCs) were isolated, cultured and identified from one patient with CCD and compared with normal controls. This CCD patient was confirmed to have a heterozygous frameshift mutation of RUNX2 (c.514delT, p.Ser172fs) in the previous study. The results showed that the proliferation abilities of DFCs and PDLCs were both disturbed by the RUNX2 mutation in the CCD patient compared with the normal control. A co-culture system of these cells with human peripheral blood mononuclear cells was then used to investigate the effect of RUNX2 mutation on osteoclastogenesis. We found that the RUNX2 mutation in CCD reduced the expression of osteoclast-related genes, such as RUNX2, CTR, CTSK, RANKL and OPG The ability of osteoclastogenesis in DFCs and PDLCs detected by tartrate-resistant acid phosphatase staining in the co-culture system was also reduced by the RUNX2 mutation compared with the normal control. These outcomes indicate that the RUNX2 mutation disturbs the modulatory effects of DFCs and PDLCs on the differentiation of osteoclasts and osteoblasts, thereby interfering with bone remodelling. These effects may contribute in part to the pathological manifestations of retention of primary teeth and delayed eruption of permanent teeth in patients with CCD.
authors: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China.
authors: Xiangyu
authors: X
authors: Sun
authors: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China.
authors: Xiaozhe
authors: X
authors: Wang
authors: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China.
authors: Chenying
authors: C
authors: Zhang
authors: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China.
authors: Yang
authors: Y
authors: Liu
authors: Department of Stomatology, Dongzhimen Hospital of Beijing University of Chinese Medicine, 5 Haiyuncang Lane, Dongcheng District, Beijing 100081, People's Republic of China.
authors: Xiang
authors: X
authors: Yang
authors: Outpatient Center of Peking University School and Hospital of Stomatology, A37 Xishiku Street, Xicheng District, Beijing 100081, People's Republic of China.
authors: Wenjuan
authors: W
authors: Yan
authors: Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China and.
authors: Zhongning
authors: Z
authors: Liu
authors: Central Laboratory, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China.
authors: Yixiang
authors: Y
authors: Wang
authors: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing 100081, People's Republic of China, zhengsg86@gmail.com.
authors: Shuguo
authors: S
authors: Zheng
mesh_terms: D016723:Bone Remodeling; D049109:Cell Proliferation; D002648:Child; D002973:Cleidocranial Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003795:Dental Sac / Q000503:physiopathology; D005260:Female; D016368:Frameshift Mutation; D005786:Gene Expression Regulation; D006579:Heterozygote; D006801:Humans; D010010:Osteoclasts / Q000378:metabolism* / Q000502:physiology; D010513:Periodontal Ligament / Q000503:physiopathology
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human