Bisphosphonate inhibits the expression of cyclin A2 at the transcriptional level in normal human oral keratinocytes.

Nitrogen-containing bisphosphonates (N-BPs) are the most widely used anti-resorptive agents in the treatment of bone-related diseases. N-BPs inhibit bone resorption by specifically targeting osteoclasts, bone-resorbing cells. However, soft tissue toxicity, such as oral or gastrointestinal (GI) ulcerations has frequently been reported in N-BP users, suggesting that N-BPs may also directly target cells other than osteoclasts. Previously, we reported that BPs inhibit proliferation without inducing the apoptosis of normal human oral keratinocytes (NHOKs). However, the molecular mechanisms through which N-BPs inhibit the proliferation of NHOKs are not yet fully understood. In this study, we performed gene expression profiling in N-BP-treated NHOKs and identified cyclin A2 as one of the most commonly downregulated genes. When the NHOKs were treated with N-BPs, we found that the level of cyclin A2 was suppressed in a dose- and time-dependent manner. In addition, the protein level of cyclin A2 was also significantly lower in oral epithelial cells in N-BP-treated oral mucosal tissue constructs. Cyclin A2 promoter reporter assay revealed that N-BPs inhibited the luciferase activity, indicating that the inhibition of cyclin A2 expression occurs at the transcriptional level. Furthermore, N-BPs did not alter the expression of cyclin A2 in normal human oral fibroblasts (NHOFs), suggesting that the effect of N-BPs on cyclin A2 expression may be cell-type specific. Thus, the findings of our study demonstrate that the inhibition of NHOK proliferation by N-BPs is mediated, at least in part, by the suppression of cyclin A2 expression at the transcriptional level, which may explain the underlying mechanisms of soft tissue toxicity by N-BPs.

Clinical and Molecular Perspectives of Reparative Dentin Formation: Lessons Learned from Pulp-Capping Materials and the Emerging Roles of Calcium.

The long-term use of calcium hydroxide and the recent increase in the use of hydraulic calcium-silicate cements as direct pulp-capping materials provide important clues in terms of how reparative dentin may be induced to form a "biological seal" to protect the underlying pulp tissues. In this review article, we discuss clinical and molecular perspectives of reparative dentin formation based on evidence learned from the use of these pulp-capping materials. We also discuss the emerging role of calcium as an odontoinductive component in these pulp-capping materials.

Caries-preventive activity of fluoride-containing resin-based desensitizers.

OBJECTIVE: The purpose of this study was to evaluate the effects of different desensitizing agents on the prevention of root caries when applied to root surfaces. MATERIALS AND METHODS: Thirty human roots were sectioned into quarters with a 3 × 4 mm window. A desensitizer (VX, Clinpro™ XT Varnish; SP, Seal & Protect®; or PB, Clearfil™ Protect Bond) was applied to three of the quarters in each window. Teeth were stored separately in water for one day, 30 days, or 60 days. The remaining quarter, without the application of desensitizer, served as a control. After storage in water, all specimens were subjected to pH cycling. Scanning electron microscopy was used to observe the demineralization bands created on the subsurface layer. The weight percentages of fluorine (F), silica, and calcium (Ca) were determined using electron probe microanalysis to quantify the elemental distributions in the root dentin. The concentrations of F released during a pH cycling were measured. RESULTS: For the control group, the average lesion depth was 18.92 ± 5.42 µm, and the average Ca loss was 15.66% ± 6.80% in the superficial layer and 30.44% ± 9.61% in the subsurface layer. No Ca loss occurred in the desensitizer-treated groups. All desensitizing agents remained intact for at least 60 days. F levels were increased in the hybrid layer but not in the subhybrid area. Outward release of F diminished with time. CONCLUSION: The F-containing resin-based desensitizers protected exposed root surfaces from demineralization. F liberated from the desensitizers was detected only at minimal levels.