Effect of Resveratrol on Critical-Sized Calvarial Defects of Diabetic Rats: Histometric and Gene Expression Analysis.

ABSTRACT

PURPOSE: This study investigated the influence of resveratrol (RESV) on the repair of bone critical defects in calvaria of animals with induced diabetes mellitus (DM). MATERIAL AND METHODS: One hundred rats were divided into 5 groups induced DM + RESV administration (DM + RESV; n = 20); induced DM plus placebo solution administration (DM + PLAC; n = 20); induced DM plus insulin therapy (DM + INS; n = 20); induced DM plus administration of RES and INS (DM + RESV + INS; n = 20); and nondiabetic controls (NDM; n = 20). DM was induced by intraperitoneal injection of streptozotocin 50 mg/kg 3 days before the surgical procedures. Two critical calvarial defects were created in each animal at the start of the study (day 0). Treatments were administered from day 0 to day 30 of the experiment, when animals were euthanized. One defect was processed for histometric analysis to measure closure of the bone defect. The tissue of the other defect was analyzed for quantification of bone morphogenetic protein-2 (BMP-2), osteopontin, osteoprotegerin, receptor activator of nuclear factor-κB ligand, runt-related transcription factor-2, osterix (Osx), ß-catenin, lipoprotein receptor-related protein-5, and dikkop-1 mRNA by quantitative polymerase chain reaction. RESULTS: Histometric results showed that the DM + RESV, DM + RESV + INS, and NDM groups exhibited greater closure of the bone defects compared with the PLAC- or INS-treated groups (P < .05). Diabetic animals treated with RESV plus INS showed higher levels of BMP-2 and Osx; Osx also was positively increased in animals treated with INS alone (P < .05). CONCLUSIONS: The use of RESV, regardless of the presence of INS, positively influenced bone repair in animals with induced DM. Further, the combination of INS plus RESV was necessary for the modulation of BMP-2 gene expression.