Basic research to clarify the mechanism of delayed tooth eruption in cleidocranial dysplasia

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1) The cause of the Cleidocranial dysplasia (CCD), characterized by hypoplastic clavicle and cranial bones, is known as a gene mutation of RUNX2/CBFA1. Runx2/Cbfal is a mouse homolog of RUNX2/CBFA1 and heterozygous Runx2/Cbfa1 gene-deficient mice of this gene resembles to the bone abnormalities in CCD. CCD frequently accompanies supernumerary teeth and impaction and delayed eruption of teeth, however, these causes are yet not known. To clarify these points, teeth and periodontal tissues were examined in heterozygous mice. The number of teeth or the formation of cementum and periodontal ligament did not show difference between heterozygous and normal mice. However, the timing of tooth eruption into the oral cavity was significantly delayed in the former than in the latter. The osteoclast number located in the eruption pathway was significantly lower in the former., These observations suggest that impaired osteoclast recruitment due to the haploinsufficiency of RUNX2/CBFA1 as one of the cause of the delayed tooth eruption in CCD.2) The process of tooth eruption is divided into the eruption 'pathway formation and vertical tooth movement. We reported the contribution and function of parathyroid hormone-related protein (PTHrP) and RANKL in the former process. We also developed a novel culture system to assay the osteoclast formation and activation using the erupting teeth and periodontal tissues.3) Since the periodontal ligament (PDL) is known to play an important role during the tooth eruption, DNA microarray was carried out to compare the gene expression of PDL isolated from erupting and non-erupting teeth. Interestingly, the expression of CALBINDINi, which is also known to show high expression in the compression side of the PDL during the experimental tooth movement in rats, was dramatically higher in PDLs from erupting teeth than non-erupting teeth.