Search

The discoidin domain receptors, DDR1 and DDR2, are nonintegrin collagen receptors and tyrosine kinases. DDRs regulate cell functions, and their extracellular domains affect collagen fibrillogenesis and mineralization. Based on the collagenous nature of dentoalveolar tissues, we hypothesized that DDR1 plays an important role in dentoalveolar development and function. Radiography, micro-computed tomography (micro-CT), histology, histomorphometry, in situ hybridization (ISH), immunohistochemistry (IHC), and transmission electron microscopy (TEM) were used to analyze Ddr1 knockout ( Ddr1 -/- ) mice and wild-type (WT) controls at 1, 2, and 9 mo, and ISH and quantitative polymerase chain reaction (qPCR) were employed to assess Ddr1 / DDR1 messenger RNA expression in mouse and human tissues. Radiographic images showed normal molars but abnormal mandibular condyles, as well as alveolar bone loss in Ddr1 -/- mice versus WT controls at 9 mo. Histological, histomorphometric, micro-CT, and TEM analyses indicated no differences in enamel or dentin Ddr1 -/- versus WT molars. Total volumes (TVs) and bone volumes (BVs) of subchondral and ramus bone of Ddr1 -/- versus WT condyles were increased and bone volume fraction (BV/TV) was reduced at 1 and 9 mo. There were no differences in alveolar bone volume at 1 mo, but at 9 mo, severe periodontal defects and significant alveolar bone loss (14%; P  < 0.0001) were evident in Ddr1 -/- versus WT mandibles. Histology, ISH, and IHC revealed disrupted junctional epithelium, connective tissue destruction, bacterial invasion, increased neutrophil infiltration, upregulation of cytokines including macrophage colony-stimulating factor, and 3-fold increased osteoclast numbers ( P  < 0.05) in Ddr1 -/- versus WT periodontia at 9 mo. In normal mouse tissues, ISH and qPCR revealed Ddr1 expression in basal cell layers of the oral epithelia and in immune cells. We confirmed a similar expression pattern in human oral epithelium by ISH and qPCR. We propose that DDR1 plays an important role in periodontal homeostasis and that absence of DDR1 predisposes mice to periodontal breakdown.

Clonidine has recently been used as a pre-operative medication and sedative/anxiolytic drug. Its extended duration of action makes it suitable for longer procedures. In this randomized, crossover, placebo-controlled clinical trial, we characterized the effects of oral clonidine pre-treatment on intravenous diazepam/meperidine sedation using the bi-spectral index (BIS) in 13 participants. Clonidine significantly increased the numbers of BIS-depressed readings and percent memory loss during sedation, while reducing total diazepam and post-operative analgesic dosages by 44% and 55%, respectively. Systolic, diastolic, and mean arterial blood pressures, as well as pulse rates, were reduced. Respiratory rate, oxygen saturation, end-tidal CO(2), and recovery from sedation were unchanged. Participants, surgeons, and sedationists preferred clonidine over the placebo. Clonidine pre-treatment increased and prolonged sedation and amnesia and stabilized vital signs while significantly decreasing diazepam and post-operative analgesic usage. These results suggest that pre-operative clonidine administration could be a useful supplement to intravenous sedation for dental procedures of long duration.

Papillon-Lefèvre syndrome (PLS), palmoplantar hyperkeratosis with periodontitis, has been genetically characterized. However, suspected associated immune dysfunctions remain elusive. The purpose of this study was to evaluate peripheral blood lymphocyte levels and natural killer (NK) cell cytotoxicity in PLS. Twenty patients and 20 healthy controls were examined. Peripheral blood lymphocytes were analyzed by flow cytometry for surface markers. NK cell cytotoxicity against K562 cells was determined by means of a 51Cr release assay. White blood cell differential and proportions of B-, T-, T-helper, T-suppressor, and NK cells revealed only sporadic borderline variations from control values. In contrast, NK cell cytotoxicity was consistently and severely depressed (32-53% of control values) in all patients. To the best of our knowledge, this newly described impairment of NK cell cytotoxic function is the first consistent immune dysfunction reported in PLS. This suggests that the impaired NK cell cytotoxicity might contribute to the pathogenesis of PLS-associated periodontitis.

Evidence indicates that incisor crown form correlates with clinical periodontal features. It was hypothesized that incisor crown form may explain subject differences in gingivitis expression. The present experimental gingivitis study aimed to assess the effect of incisor crown form on plaque accumulation and gingival inflammation, and on individual susceptibility to plaque-induced gingivitis. Eighty-five periodontally healthy subjects were evaluated. A negative correlation was found between incisor crown width/crown length ratio and bleeding score (p = 0.045). From the 85 subjects, two groups of subjects with either 'long-narrow' or 'short-wide' incisor form were identified. The 'long-narrow' group had a significantly higher bleeding score than the 'short-wide' group (p = 0.014). No significant differences were found in the incisor crown width/crown length ratio between previously identified 'high responder' and 'low responder' subjects (Trombelli et al., 2004a). In conclusion, incisor crown form appears to affect the bleeding response of inflamed gingival tissues, while it exerts no influence on explaining differences in individuals' susceptibility to plaque-induced gingivitis.

Interleukin-10 regulates pro-inflammatory cytokines, including those implicated in alveolar bone resorption. We hypothesized that lack of interleukin-10 leads to increased alveolar bone resorption. Male interleukin-10(-/-) mice, on 129/SvEv and C57BL/6J background, were compared with age-, sex-, and strain-matched interleukin-10(+/+) controls for alveolar bone loss. Immunoblotting was used for analysis of serum reactivity against bacteria associated with colitis and periodontitis. Interleukin-10(-/-) mice had significantly greater alveolar bone loss than interleukin-10(+/+) mice (p = 0.006). The 30-40% greater alveolar bone loss in interleukin-10(-/-) mice was evident in both strains, with C57BL/6J interleukin-10(-/-) mice exhibiting the most bone loss. Immunoblotting revealed distinct interleukin-10(-/-) serum reactivity against Bacteroides vulgatus, B. fragilis, Prevotella intermedia, and, to a lesser extent, against B. forsythus. The results of the present study suggest that lack of interleukin-10 leads to accelerated alveolar bone loss.