Background: TGF-␤1 positively and negatively regulates osteoblast differentiation. Results: Repeated TGF-␤1 negatively regulates osteoblast differentiation caused by inhibiting IGF-1 expression and Akt phosphorylation. Conclusion: Prolonged TGF-␤1 treatment inhibits osteoblast differentiation of mesenchymal stem cells via the suppression of the IGF-1 signaling pathway. Significance: IGF-1 administration may recover the suppression of osteogenesis and promotion of bone resorption due to chronic inflammation by TGF-␤1.

This study investigated the effect of various treatments with TGF-β1 in osteogenic differentiation of human periodontal ligament (HPDL) cells.HPDL cells were treated with single 1 ng/ml, 100 ng/ml or multiple (12-h intervals) 1 ng/ml TGF-β1. Alkaline phosphatase (ALP) activity was detected by ALP activity staining at 4 days. Phospho-Smad3 was detected by western blotting and transcription of osteogenic differentiation markers (RUNX2, ALPL, IBSP: bone sialoprotein, BGLAP: osteocalcin) were determined by real-time PCR at various culture periods. Cells were pretreated with or without SB505124, a TGF-β/Smad pathway inhibitor, for 1 h before 1 ng/ml TGF-β1 treatment at 12-h intervals. ALP activity and phosphorylated Smad3 were detected.Single treatment with 1 ng/ml TGF-β1 significantly induced Smad3 phosphorylation, subsequent ALP upregulation and transcription of osteogenic differentiation markers, compared to these inductions with 100 ng/ml TGF-β1 treatment. In multiple treatments with 1 ng/ml TGF-β1 at 12-h intervals, only the first treatment significantly induced Smad3 phosphorylation but not the succeeding treatments. Inductive effects of single 1 ng/ml TGF-β1 in osteogenic differentiation were almost completely abolished by multiple treatments. Furthermore, multiple treatments with 1 ng/ml TGF-β1 did not induce ALP activity although the TGF-β/Smad pathway was inhibited by SB505124.Single treatment with low dose TGF-β1 significantly induced osteogenic differentiation. Multiple treatments inhibited osteogenic differentiation despite inhibition of TGF-β/Smad pathway. These findings suggest that TGF-β1 both positively and negatively regulates osteogenic differentiation and the inhibitory effect may be mediated by the non-Smad signaling pathway in HPDL cells.

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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.

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.