Regulation Of Adipogenesis By Grape Seed Procyanidin Extract:Implications In Obesity-impaired Fracture Healing

Impaired fracture healing or fracture nonunion is a growing concern for orthopedic surgeons.Diaphyseal nonunions in the closed tibia fracture and femur fracture are estimated to occur 4.5-8%after modern intramedullary nailing,which is even higher in open fractures.Obesity is known to be significant independent risk factors for impaired or delayed fracture healing.With nearly 34%of the US population being obese,and this number is projected to climb significantly in the coming decade,the incidence of obesity impaired fracture healing will achieve more concerns.There is a high socioeconomic burden for fracture nonunions driven mainly by indirect costs.Despite these sobering statistics,the basis for delayed healing in obesity is not determined and begs investigation for the purpose of better therapeutic strategies.Literatures showed that fracture callus adiposity is a key phenotype in obesity impaired fracture delayed healing.Procyanidins have been studied heavily due to their benefits for cancer,cardiovascular disease,type 2 diabetes,and ulcerative colitis.In this present study,we found that grape seed procyanidins extract could inhibits adipogenesis of 3T3-L1 cells by targeting PPARy and this effect is mediated,at least partially,by microRNA-483-5p.Our animal studies demonstrated that,compared with the mice fed with low fat diet,tibia fracture healing,which was tested by X-ray,microCT and biomechanical test,is impaired by fed with high fat diet.Our histological studies proven that there is fracture callus adiposity in the mice fed with high fat diet as well.Intriguingly,after feeding them with high fat diet and grape seed procyanidins extract at the same time,our results of X-ray,microCT and biomechanical test showed that there is no significant difference compared with the mice fed with low fat diet.Histological results showed there is significant less adiposity as well.Taken together,our results revealed that grape seed procyanidins extract could inhibit the adipogenesis during callus formation by targeting PPARy,which is mediated by microRNA-130b.Grape seed procyanidins extract is therefore a promising candidate for preventing of obesity impaired fracture healings.