Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts.

Physical forces play a critical role in the survival and proliferation of many cell types, including fibroblasts. Gingival fibroblasts are exposed to mechanical stress during mastication, orthodontic tooth movement, and wound healing following periodontal surgery. The aim of this study was to examine the effect of mechanical strain on human gingival fibroblasts (hGF). Cells were subjected to short-term (up to 60 min) and long-term (up to 48 hrs) 20% average elongation at 0.1 Hz. We monitored survival signaling by evaluating the phosphorylation status and localization of Forkhead box (FoxO) family members, which are mediators of apoptosis. We also examined strain-induced proliferation by measuring the level of proliferating cell nuclear antigen (PCNA). We observed that cyclic strain caused the phosphorylation and retention in the cytoplasm of FoxO family members. Moreover, mechanical strain resulted in increased ERK kinase phosphorylation and PCNA expression. In conclusion, cyclic strain delivers anti-apoptotic and proliferative stimuli to hGF.

Evaluation of maxillary sinus membrane response following elevation with the crestal osteotome technique in human cadavers.

Implant placement in the posterior maxilla often requires elevation of the sinus floor, which can be achieved through either the modified Caldwell-Luc or the crestal osteotome technique. The objectives of this study were to evaluate (a) the resistance to perforation of maxillary sinus membranes obtained from formaldehyde-fixed cadavers in vitro, (b) the frequency and extent of membrane perforations occurring after sinus floor elevation in cadavers using the crestal approach, and (c) the amount of membrane elevation (doming) that can be achieved using the crestal approach. Pretreatment of maxillary sinus membrane tissues with commonly used tissue softeners did not have a statistically significant effect on resistance to perforation. Maxillary sinus membranes were elevated 4 to 8 mm in formaldehyde-fixed cadavers using the osteotome technique; implants were placed. Of the 25 sites that received implants, only 6 showed perforations, as assessed by double-blind investigation after dissection of the lateral wall of the nose, allowing direct examination of the sinus cavity. Perforations were categorized as Class I (< or = 2 mm with exposure of the implant into the sinus cavity and loss of doming); Class II perforations (> or = 2 mm) were associated with proximity of the osteotomy site to the medial wall of the sinus or the presence of septae. These results indicated that the crestal osteotome approach compared favorably to the modified Caldwell-Luc technique as it relates to the frequency of maxillary sinus membrane perforations and the degree of achievable membrane elevation.

Combined treatment of periodontal disease and benign mucous membrane pemphigoid. Case report with 8 years maintenance.

BACKGROUND: Desquamative gingivitis may be the clinical manifestation of one of several systemic diseases. The clinical course of the disease can be complicated by plaque-associated periodontitis. However, there is no information currently available for the concurrent management of both conditions. CASE REPORT AND RESULTS: This paper presents the treatment and 8-year maintenance of a patient with periodontal disease and benign mucous membrane pemphigoid (BMMP). The first phase of treatment included oral hygiene instructions and local corticosteroid administration, followed by scaling and root planing. The patient's compliance and excellent response to therapy allowed for subsequent surgical pocket elimination and augmentation of the zone of keratinized tissue for prosthetic reasons. Over the following 8 years, the patient's periodontal condition remained stable even though periodontal maintenance was erratic. For the control of BMMP, intermittent administration of corticosteroids was necessary, without any significant local or systemic side effects. CONCLUSIONS: We suggest that combined treatment and long-term maintenance of BMMP and periodontitis are feasible under certain conditions and propose a clinical protocol for treatment which could serve as a guideline for similar conditions.

Nitric oxide acts in conjunction with proinflammatory cytokines to promote cell death in osteoblasts.

Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin-1 beta are known modulators of bone remodeling in vitro and in vivo. The same cytokines induce the production of nitric oxide (NO) in various cell types, including osteoblasts and osteoclasts, and NO has recently been implicated in the regulation of bone resorption. We investigated the relationship between NO levels and cell viability in MC3T3-E1, a well-characterized osteoblastic cell line. NO donors at high concentrations (> or = 0.5 mM) produce a significant cytotoxic effect over a 48 h period. Various combinations of the three cytokines strongly promote endogenous NO production, and high NO levels are correlated with the loss of cell viability. Although TNF-alpha produces NO-independent cytotoxicity, NO greatly enhances this cytotoxic effect. Human and mouse TNF-alpha differ in their cytotoxic effects, and human TNF-alpha induces lower levels of NO production. In cocultures of RAW 264.7 mouse macrophages stimulated with lipopolysaccharide and IFN-gamma, and untreated MC3T3-E1 osteoblasts, addition of anti-TNF-alpha antibody and inhibition of NO synthesis have additive, protective effects on osteoblast viability. NO cytotoxicity involves an apoptotic mechanism. Our results underline the importance of NO and TNF-alpha as cytotoxic mediators in the osseous microenvironment and might explain the observed deficiency of bone formation in inflammatory sites.

Cytokines induce nitric oxide production in mouse osteoblasts.

MC3T3-E1 mouse clonal osteogenic cells were incubated with interferon-gamma, interleukin-1 beta, tumor necrosis factor-alpha, and E. coli lipopolysaccharide. TNF alpha, IL-1 beta, and LPS caused a dose- and time-dependent increase of nitrite (NO2-), the stable metabolite of nitric oxide (NO), in conditioned media over 48 hours, while IFN gamma had a minimal effect. Different combinations of the same factors caused a synergistic enhancement of NO2- accumulation, except for IL-1 beta with LPS. The earliest detectable NO2- production was at 6-9 hours, with continued accumulation over 48 hours. NO2- production was inhibited dose-dependently by three arginine analogs known to be specific inhibitors of NO synthase, as well as by actinomycin D, cycloheximide, and dexamethasone; EGTA or indomethacin had a small inhibitory effect. It is concluded that osteoblast-like cells can be induced by proinflammatory cytokines and bacterial endotoxin to produce NO, which can play an important role in bone pathophysiology.

The role of cytokines in the pathogenesis of periodontal disease.

Recent advances in cellular and molecular biology have allowed investigators to better understand the mechanisms of inflammatory and immune responses in many infectious diseases. Soluble mediators produced by various inflammatory and structural cells, collectively called cytokines, have been shown to play a crucial role in the pathogenesis of most of these diseases, including periodontal disease. This paper globally reviews recently reported findings implicating cytokines in periodontal pathophysiology. Inflammatory mediators, such as interleukin-1, tumor necrosis factor-alpha, and interferon-gamma, known to regulate bone resorptive activity are present in diseased periodontal tissues. Similarly, metalloproteinases, which degrade extracellular matrix, have been shown to have increased activity in diseased sites, and enhanced levels of their inhibitors correlate with absence of disease activity. Finally, certain polypeptide growth factors originally known to play a role in wound healing are now shown to have a significant effect in inflammatory responses.