Endogenous PTH Deficiency Impairs Fracture Healing and Impedes the Fracture-Healing Efficacy of Exogenous PTH(1-34) 英文参考文献.docVIP

EndogenousPTHDeficiencyImpairsFractureHealing andImpedestheFracture-HealingEfficacyofExogenous PTH(1-34) YongxinRen1,3.,BoLiu1,2.,YuxuFeng1,3,LeiShu3,XiaojianCao1,AndrewKaraplis4,DavidGoltzman4, DengshunMiao3* 1Department of Orthopaedics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, China, 2Department of Orthopaedics, The Liyang People’s Hospital, Changzhou, China, 3The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China, 4DepartmentofMedicine,McGillUniversity,Montreal,Canada Abstract Background:AlthoughthecapacityofexogenousPTH1-34toenhancetherateofbonerepairiswellestablishedinanimal models,ourunderstandingofthemechanism(s)wherebyPTHinducesananabolicresponseduringskeletalrepairremains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenousPTHwouldinfluencethefracture-healingcapacityofexogenousPTH. Methodology/Principal Findings: Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth2/2) mice. Mice received daily injections of vehicle or of PTH1-34(80mg/kg)for1–4weekspost-fracture,andcallustissuepropertieswereanalyzedat1,2and4weekspost-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle- treated and PTH-treated Pth2/2 mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralizedcallusareas,bonycallusareas,osteoblastnumberandactivity,osteoclastnumberandsurfaceincallustissues wereallreducedinvehicle-treatedandPTH-treatedPth2/2 micecomparedtovehicle-treatedandPTH-treatedwild-type mice,butwereincreasedinPTH-treatedwild-typeandPth2/2micecomparedtovehicle-treatedwild-typeandPth2/2 mice. Conclusions/Significance:AbsenceofendogenousPTH1-84impedesbonefracturehealing.ExogenousPTH1-34canactin the absence of endo