title: Abnormal differentiation of dental pulp cells in cleidocranial dysplasia.
abstract: Cleidocranial dysplasia (CCD) is a skeletal dysplasia caused by heterozygous mutations of RUNX2, a gene that is essential for the mineralization of bone and tooth. We isolated primary dental pulp cells from a 10-y-old patient and tested their proliferative capacity, alkaline phosphatase activity, and ability to form mineralized nodules, in comparison with those from 7 healthy children. All these measures were reduced in primary dental pulp cells from the CCD patient. The expression of the osteoblast/odontoblast-associated genes RUNX2, ALP, OCN, and DSPP was also found to be significantly decreased in the primary dental pulp cells of the CCD patient. The osteoclast-related markers TRAP, CTSK, CTR, and MMP9 were decreased in primary dental pulp cells cocultured with human peripheral blood mononuclear cells. Moreover, the expression of RANKL and the ratio of RANKL/OPG were both reduced in the cells from the CCD patient, indicating that the RUNX2 mutation interfered with the bone-remodeling pathway and decreased the capacity of primary dental pulp cells to support osteoclast differentiation. These effects may be partly responsible for the defects in tooth development and the retention of primary teeth that is typical of CCD.
authors.affiliation: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China Department of Pediatric Dentistry, the First Division, Peking University School and Hospital of Stomatology, Xicheng District, Beijing, China.
authors.forename: W J
authors.initials: WJ
authors.lastname: Yan
authors.affiliation: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Department of Stomatology, Dongzhimen Hospital Beijing University of Chinese Medicine, Dongcheng District, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Prosthodontics, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
authors.forename: Z N
authors.initials: ZN
authors.lastname: Liu
authors.affiliation: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Wang
authors.affiliation: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
authors.forename: X Y
authors.initials: XY
authors.lastname: Sun
authors.affiliation: Central Laboratory, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Wang
authors.affiliation: Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, Haidian District, Beijing, China zhengsg86@gmail.com kqwangyx@gmail.com.
authors.forename: S G
authors.initials: SG
authors.lastname: Zheng
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D000469:Alkaline Phosphatase / Q000032:analysis; D016723:Bone Remodeling / Q000502:physiology; D002113:Calcification, Physiologic / Q000502:physiology; D056657:Cathepsin K / Q000032:analysis; D027682:Cation Transport Proteins / Q000032:analysis; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002973:Cleidocranial Dysplasia / Q000235:genetics / Q000473:pathology*; D018920:Coculture Techniques; D050659:Core Binding Factor Alpha 1 Subunit / Q000032:analysis / Q000235:genetics; D003782:Dental Pulp / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D007527:Isoenzymes / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D009804:Odontoblasts / Q000473:pathology; D010006:Osteoblasts / Q000473:pathology; D015675:Osteocalcin / Q000032:analysis; D010010:Osteoclasts / Q000473:pathology; D053244:Osteoprotegerin / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis; D053245:RANK Ligand / Q000032:analysis; D012795:Sialoglycoproteins / Q000032:analysis; D000071681:Tartrate-Resistant Acid Phosphatase; D000099311:Dentin Sialophosphoprotein
chemical_list: D000135:Acid Phosphatase; D000469:Alkaline Phosphatase; D056657:Cathepsin K; D027682:Cation Transport Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; D007527:Isoenzymes; D020780:Matrix Metalloproteinase 9; D015675:Osteocalcin; D053244:Osteoprotegerin; D010750:Phosphoproteins; D053245:RANK Ligand; D012795:Sialoglycoproteins; D000071681:Tartrate-Resistant Acid Phosphatase; D000099311:Dentin Sialophosphoprotein; C493709:RUNX2 protein, human; C505688:TNFSF11 protein, human; C534130:CTSK protein, human; C579270:MMP9 protein, human
keywords: bone remodeling/regeneration; cell biology; craniofacial anomalies; craniofacial biology/genetics; osteoclasts; osteogenesis