Clinical and radiographic findings and usefulness of computed tomographic assessment in two children with regional odontodysplasia.

Regional odontodysplasia is a rare, severe, and nonhereditary developmental disorder in tooth formation and involves epithelial and mesenchymal-derived dental tissue. On radiographs, affected teeth have an abnormal morphology, a hypoplastic crown, and only a faint outline of hard tissue, a condition termed "ghost teeth." We report clinical and radiographic findings from two children with regional odontodysplasia. Using computed tomography (CT), we calculated attenuation coefficients (i.e., Hounsfield units) for affected teeth and assessed the condition of dental follicles. To measure density, regions of interest were delimited and CT values were calculated. In our two patients, the CT values for enamel were lower in affected teeth than in sound teeth, while CT values for dentin were similar for affected and sound teeth. The average CT value for dental follicles in affected teeth was about 65 to 120, which suggests that dense fibrous connective tissues or hard tissue-like structures might be present in dental follicles. Analysis of CT values may be quite useful in the diagnosis and treatment of regional odontodysplasia.

Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation.

The periodontal ligament (PDL), a connective tissue located between the cementum of teeth and the alveolar bone of mandibula, plays a crucial role in the maintenance and regeneration of periodontal tissues. The PDL contains fibroblastic cells of a heterogeneous cell population, from which we have established several cell lines previously. To analyze characteristics unique for PDL at a molecular level, we performed cDNA microarray analysis of the PDL cells versus MC3T3-E1 osteoblastic cells. The analysis followed by validation by reverse transcription-polymerase chain reaction and immunochemical staining revealed that endoglin, which had been shown to associate with transforming growth factor (TGF)-beta and bone morphogenetic proteins (BMPs) as signaling modulators, was abundantly expressed in PDL cells but absent in osteoblastic cells. The knockdown of endoglin greatly suppressed the BMP-2-induced osteoblastic differentiation of PDL cells and subsequent mineralization. Interestingly, the endoglin knockdown did not alter the level of Smad-1/5/8 phosphorylation induced by BMP-2, while it suppressed the BMP-2-induced expression of Id1, a representative BMP-responsive gene. Therefore, it is conceivable that endoglin regulates the expression of BMP-2-responsive genes in PDL cells at some site downstream of Smad-1/5/8 phosphorylation. Alternatively, we found that Smad-2 as well as Smad-1/5/8 was phosphorylated by BMP-2 in the PDL cells, and that the BMP-2-induced Smad-2 phosphorylation was suppressed by the endoglin knockdown. These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells.

Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts.

Ligaments and tendons are comprised of tough yet flexible connective tissue. Little is known, however, about the precise characteristics of the cells in ligaments and tendons due to the absence of specific markers and cell lines. We recently reported a periodontal ligament cell line, PDL-L2, with suppressed Runx2/Osf2 transcriptional activity and an inability to form mineralized nodules. The present study demonstrates that the homeobox protein Msx2 is a key factor in suppressing those two functions. Msx2 colocalizes with Runx2/Osf2 and suppresses its activity cooperatively, acting with another corepressor, TLE1, as a complex to recruit histone deacetylase 1 activity. Reverse transcription-PCR and in situ hybridization demonstrated that Msx2 expression is higher in periodontal ligament and tendon cells than in osteoblasts. Stable reduction of Msx2 expression in PDL-L2 cells induces osteoblastic differentiation, thereby causing matrix mineralization. Conversely, stable, forced Msx2 expression in MC3T3-E1 cells prevented osteoblast differentiation and matrix mineralization. Msx2-induced suppression of osteoblast differentiation was repressed by bone morphogenetic protein 2. In addition, Msx2 was downregulated in a symptom- and calcification-dependent manner at the affected region in patients with ossification of the posterior longitudinal ligament. Our findings indicate that Msx2 plays a central role in preventing ligaments and tendons from mineralizing.