title: The role of periodontal ligament cells in delayed tooth eruption in patients with cleidocranial dysostosis.
abstract: OBJECTIVE
  The clinical appearance of patients with cleidocranial dysplasia (CCD), which is caused by mutations in the RUNX2 gene, is characterized by anomalies of the clavicles, thorax, spine, pelvis and extremities and by disturbances of the skull and tooth development. Of orthodontic relevance are multiple supernumerary teeth associated with delayed tooth eruption. The present investigation is based on the hypothesis that an altered phenotypic expression of periodontal ligament (PDL) cells from CCD patients and a reduced ability of those cells to support the differentiation of bone-resorbing osteoclasts might contribute to delayed tooth eruption.
  
  
  METHODS
  To test this hypothesis, PDL cells from healthy donors and from two patients with clinically and molecular biologically diagnosed CCD were characterized for the basal and induced mRNA expression of osteoblast marker genes. The physiological relevance of the findings for the differentiation of osteoclasts was examined in an osteoclast assay, as well as in a co-culture model of PDL cells and osteoclast precursors.
  
  
  RESULTS
  Both CCD patients displayed missense mutations of the RUNX2 gene. The in vitro experiments revealed an unaltered expression of RUNX2 mRNA, however especially in CCD patient 2 there was a reduced basal expression of mRNA for the key regulatory gene for bone remodeling RANKL. Furthermore, compared to the control cells from healthy donors, these factors were less inducible by stimulation of the cultures with 1alpha,25(OH)(2)D(3). In the osteoclast assays as well as in the co-culture experiments, PDL cells from the CCD patients showed a reduced capacity to induce the differentiation of active osteoclasts.
  
  
  CONCLUSIONS
  These data indicate that PDL cells from CCD patients express a less distinctive osteoblastic phenotype resulting in an impaired ability to support osteoclastogenesis which might, in part, account for the delayed tooth eruption that can be observed clinically.
authors: Department of Orthodontics, University of Bonn, Germany. s.lossdoerfer@gmx.de
authors: Stefan
authors: S
authors: Lossdörfer
authors: Bassel
authors: B
authors: Abou Jamra
authors: Birgit
authors: B
authors: Rath-Deschner
authors: Werner
authors: W
authors: Götz
authors: Rami
authors: R
authors: Abou Jamra
authors: Bert
authors: B
authors: Braumann
authors: Andreas
authors: A
authors: Jäger
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D002973:Cleidocranial Dysplasia / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000473:pathology*; D010513:Periodontal Ligament / Q000473:pathology* / Q000503:physiopathology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014078:Tooth Eruption; D014097:Tooth, Unerupted / Q000150:complications / Q000235:genetics* / Q000473:pathology*
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C493709:RUNX2 protein, human