The Role Of Transmembrane Serine Protease Corin In Bone Development And Fracture Repair

Objective:Corin is a serine protease expressed in the developing bone,heart,pregnant uterus and kidney.It has been studied extensively that Corin is a critical regulator of vascular system and blood pressure.The physiological function of Corin in developming bone is still unknown.In this study,we want to test the role of Corin in bone development and the influence in the bone healing in the fracture model.Method:The newborn Wild-type and Corin knockout long bones were compared via Alcian blue and Alizarin red staining to determine the effect of Corin deficiency on bone development.The mRNAs of MMP13 and VEGF in tibial of newborn mice was analyzed by qPCR.A femur fracture model was introduce by a 3-point bengding method.At different points,the mice were anesthetized by X-ray radiography,micro-CT scanning and histological analyses.Result:The ossified regions of the long bone in Corin-/-mice were shorter than in WT mice.In Corin knockout mice,the expressions of MMP13 and VEGF,the marker of Hypertrophic chondrocyte,were reduced throughout the tibial(p<0.05).At 2,4 and 6 w post-surgery,the callus area were larger in the Corin-/-group(p<0.05).But by 8 w,the callus area was similar in two groups.As analyzed in reconstructed micro-CT scanning,the total bone volume was greater in WT mice at all time points.At 6 and 8 w,WT mice showed higher BV/TV ratio than in Corin-/-group(p<0.05).By histological analysis,the callus in the WT mice indicated a faster healing process in this group.Conclusion:In this study,we observed bone formation delay in Corin knockout mice.In mouse femoral fracture models,the absence of Corin can markedly postpone the bone healing process.