Abstract
BackgroundRapid wound healing of oral soft tissue may reduce the opportunity of infection and discomfort of patients. Previous studies have demonstrated that enhancement of angiogenesis is an effective way to accelerate wound repair. In this study, to enhance angiogenesis and healing of palatal wounds, dimethyloxalylglycine (DMOG) was applied to a rat palatal wound model. DMOG is known to inhibit oxygen-dependent degradation of hypoxia inducible factor-1 alpha (HIF-1α), which can lead to up-regulation of angiogenesis markers, favoring wound repair. We also evaluated the effects of DMOG on cell migration and HIF-1α expression of rat palatal (RP) cells. Furthermore, mRNA and protein expression of vascular endothelial growth factor (VEGF) were analyzed in DMOG-treated RP cells.MethodsPrimary cultures of rat palatal (RP) cells were obtained from Sprague–Dawley (SD) rats. Effects of DMOG on cell viability and migration of RP cells were evaluated by using a formazan and culture insert, respectively. VEGF mRNA was observed by real-time PCR, and VEGF and HIF-1α proteins were detected by Western blotting. For the animal study, excisional wounds, 3 mm in diameter, were made at the central part of the palate of SD rats. DMOG with hyaluronic acid ointment was topically applied three times during 1 week, and then wound closures were quantitated photographically and histologically.ResultsDMOG was cytotoxic to RP cells at concentrations higher than 2 mM and did not affect cell migration at non-cytotoxic concentrations. mRNA and protein expression of VEGF were significantly stimulated by DMOG treatment. The protein level of HIF-1α was also stabilized in RP cells by DMOG. In the animal study, groups treated with 1 mg/ml DMOG showed an increase of rat palatal wound contractures.ConclusionsDMOG enhanced wound healing of rat palatal mucosa, which was likely due to the angiogenic effect of the agent.
Highlights
Rapid wound healing of oral soft tissue may reduce the opportunity of infection and discomfort of patients
We evaluated the effects of DMOG on cell migration and Hypoxia inducible factor-1 alpha (HIF-1α) expression of rat palatal (RP) cells
The cytotoxicity of DMOG was demonstrated at concentrations higher than 2 mM
Summary
Rapid wound healing of oral soft tissue may reduce the opportunity of infection and discomfort of patients. To enhance angiogenesis and healing of palatal wounds, dimethyloxalylglycine (DMOG) was applied to a rat palatal wound model. DMOG is known to inhibit oxygen-dependent degradation of hypoxia inducible factor-1 alpha (HIF-1α), which can lead to up-regulation of angiogenesis markers, favoring wound repair. Oral soft tissues are inevitably damaged during autogenous gingival grafting, periodontal surgery, or dental implant surgery. Recovery of soft tissue from injuries depends on wound size, location, condition of oral hygiene, and the level of immunity. Considering the importance of angiogenesis in wound healing, the application of angiogenic proteins and peptides to wounds is expected to expedite the repair of oral tissue damage if the molecules are properly delivered to the wound sites. Angiogenic small molecules which are chemically stable can be more appropriate for the harsh conditions of the oral cavity
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