title: Effects of dimethyloxalylglycine on wound healing of palatal mucosa in a rat model.
abstract: BACKGROUND
  Rapid 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.
  
  
  METHODS
  Primary 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.
  
  
  RESULTS
  DMOG 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.
  
  
  CONCLUSIONS
  DMOG enhanced wound healing of rat palatal mucosa, which was likely due to the angiogenic effect of the agent.
authors.affiliation: Department of Dental Biomaterials Science and Dental Research Institute, College of Dentistry, Seoul National University, 28 Yeonkun-dong, Chongro-ku, Seoul, 110-749, South Korea. lydia654321@hotmail.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Dental Biomaterials Science and Dental Research Institute, College of Dentistry, Seoul National University, 28 Yeonkun-dong, Chongro-ku, Seoul, 110-749, South Korea. pipichul@snu.ac.kr.
authors.forename: Hee Chul
authors.initials: HC
authors.lastname: Park
authors.affiliation: Department of Dental Biomaterials Science and Dental Research Institute, College of Dentistry, Seoul National University, 28 Yeonkun-dong, Chongro-ku, Seoul, 110-749, South Korea. kaist3414@hanmail.net.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Son
authors.affiliation: Department of Dental Biomaterials Science and Dental Research Institute, College of Dentistry, Seoul National University, 28 Yeonkun-dong, Chongro-ku, Seoul, 110-749, South Korea. yanghc@snu.ac.kr.
authors.forename: Hyeong-Cheol
authors.initials: HC
authors.lastname: Yang
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000627:therapeutic use*; D042501:Angiogenic Proteins / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006820:Hyaluronic Acid / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects; D008297:Male; D023421:Models, Animal; D009061:Mouth Mucosa / Q000187:drug effects / Q000293:injuries*; D010159:Palate / Q000187:drug effects / Q000293:injuries*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000600:Amino Acids, Dicarboxylic; D042501:Angiogenic Proteins; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D006820:Hyaluronic Acid; C040947:oxalylglycine