Inhibition of insulin-like growth factor-1 (IGF-1) expression by prolonged transforming growth factor-ß1 (TGF-ß1) administration suppresses osteoblast differentiation.

TGF-ß1 can regulate osteoblast differentiation not only positively but also negatively. However, the mechanisms of negative regulation are not well understood. We previously established the reproducible model for studying the suppression of osteoblast differentiation by repeated or high dose treatment with TGF-ß1, although single low dose TGF-ß1 strongly induced osteoblast differentiation. The mRNA expression and protein level of insulin-like growth factor-1 (IGF-1) were remarkably decreased by repeated TGF-ß1 administration in human periodontal ligament cells, human mesenchymal stem cells, and murine preosteoblast MC3T3-E1 cells. Repeated TGF-ß1 administration subsequently decreased alkaline phosphatase (ALP) activity and mRNA expression of osteoblast differentiation marker genes, such as RUNX2, ALP, and bone sialoprotein (BSP). Additionally, repeated administration significantly reduced the downstream signaling pathway of IGF-1, such as Akt phosphorylation in these cells. Surprisingly, exogenous and overexpressed IGF-1 recovered ALP activity and mRNA expression of osteoblast differentiation marker genes even with repeated TGF-ß1 administration. These facts indicate that the key mechanism of inhibition of osteoblast differentiation induced by repeated TGF-ß1 treatment is simply due to the down-regulation of IGF-1 expression. Inhibition of IGF-1 signaling using small interfering RNA (siRNA) against insulin receptor substrate-1 (IRS-1) suppressed mRNA expression of RUNX2, ALP, BSP, and IGF-1 even with single TGF-ß1 administration. This study showed that persistence of TGF-ß1 inhibited osteoblast differentiation via suppression of IGF-1 expression and subsequent down-regulation of the PI3K/Akt pathway. We think this fact could open the way to use IGF-1 as a treatment tool for bone regeneration in prolonged inflammatory disease.

Histological and immunohistochemical analyses of molar tooth germ in enamelin-deficient mouse.

Amelogenesis imperfecta (AI) is associated with mutations in a number of genes, including AMELX and ENAM. However, the precise mechanism leading to enamel malformation in different AI types remains to be elucidated. In the present study, we investigated morphological change in tooth germ obtained from ENAM-mutant mice (Enam(Rgsc521) homozygotes) as a model for human AI using histological and immunohistochemical methodologies. The results showed that ameloblasts detached from developing dentin and lost cell polarity in mutant mice at post-natal day 3. Cyst-like structures, including amelogenin-immunopositive materials, were observed between these detached cells and the dentin. No enamel-like structure, however, was observed in the cusp of the crown. These results suggest that enamelin acts as an adhesion molecule and is involved in ameloblast cell differentiation during the early stages of tooth development.

Awareness of malalignment and malocclusion in children and their guardians.

We conducted a survey on the awareness of abnormalities of dentition and occlusion in 1,904 children (0-15 years old) and their guardians (parents, grandmothers, grandfathers and siblings) on their initial visit to the Department of Pediatric Dentistry, Chiba Hospital, Tokyo Dental College. The location and type of abnormality for which the children and their guardians most commonly sought treatment were crowding of the upper and lower anterior teeth and inverted occlusion. The most common initial triggers for concern were "guardians noticed abnormalities themselves". It seems logical that where malocclusions that children and guardians can easily notice for themselves are present, they are likely to make an early visit to a clinic in the hope of improving the abnormality. We suggest that further effect is made to educate guardians of children with abnormalities of dentition and occlusion on the importance of obtaining treatment.

Clinical survey on type of restoration in deciduous teeth.

This study was conducted in 533 children with 1,634 treated teeth who visited the Pediatric Dentistry Department at the Chiba Hospital of Tokyo Dental College between January and December, 2003. Restorations on deciduous tooth were categorized by age of patient and tooth type. The following observations were made: Children aged 4 (17.9%) visited the clinic most frequently and this group had the highest number of deciduous restorations (21.3%). Among the 1,634 deciduous teeth restored, metal inlays were provided in 29.4% of total teeth restored, composite resin restorations in 27.2%, stainless-steel crowns in 25.7%, composite resin full crowns in 7.7%, glass-ionomer cement restorations in 6.6%, and amalgam restorations in 3.4%. By age, composite resin was most frequently used in children aged 1 to 3. In children aged 5 to 9, metal inlay was most frequently used. Those aged 4 received mostly stainless-steel crowns. Composite resin restorations were used mostly in anterior deciduous teeth, and metal inlays mostly in deciduous molars. Previous research indicated an increasing trend towards composite resin restorations and composite resin full crowns. The present study also confirmed such a trend. While the use of metal inlays and stainless-steel crowns tended to increase until 1987, the present study indicated a trend to decrease.