Impact of resveratrol on bone repair in rats exposed to cigarette smoke inhalation: histomorphometric and bone-related gene expression analysis

This study investigated the effect of resveratrol on bone healing and its influence on the gene expression of bone-related markers in rats exposed to cigarette smoke. Two calvarial defects were created in each of 60 rats, which were assigned equally (n = 20) to three groups: (1) resveratrol (10 mg/kg) + smoke exposure (SMK + RESV); (2) placebo + smoke exposure (SMK + PLA); or (3) placebo + no smoke exposure (NS + PLA). Substances were administered daily for 30 days following surgery. Smoke inhalation was started 7 days before surgery and continued for 30 days after surgery. One defect was processed for histomorphometric analysis and the other was used for mRNA quantification of bone-related gene expression by qPCR. The remaining defect was smaller in the SMK + RESV (2.27 ± 0.61 mm, P = 0.0003) and NS + PLA (2.17 ± 0.74 mm, P = 0.0005) groups than in the SMK + PLA group (3.12 ± 0.47 mm). Higher levels of Runx2 were observed in the NS + PLA group than in the smoke exposure groups (vs. SMK + PLA, P = 0002; vs. SMK + RESV, P = 0.052); levels of Lrp-5 were also higher in the no smoke exposure group (vs. SMK + RESV, P = 0.009; vs. SMK + PLA, P = 0.003). Resveratrol therapy decreased RANKL/OPG expression when compared to placebo (SMK + RESV vs. SMK + PLA, P = 0.017). Dkk1 levels were decreased in the SMK + RESV group when compared to the SMK + PLA (P = 0.006) and NS + PLA groups (P = 0.005). In conclusion, resveratrol optimizes the repair of critical-sized bone defects, up-regulating the gene expression of important bone remodelling markers in rats exposed to cigarette smoke inhalation.