DOI: 10.1002/ame2.12116
Alcohol-induced Wnt signaling inhibition during bone fracture healing is normalized by intermittent parathyroid hormone
treatment
Esha M.Kapania1
Taylor J.Reif2
Aaron Tsumura3
Jonathan M.Eby4
John J.Callaci4
1.Internal Medicine-Pediatric Resident,Rush University Medical Center,Chicago,IL,USA2.Limb Lengthening and Complex Reconstruction Fellowship,Hospital for Special Surgery,New York,NY,USA3.Department of Orthopaedic Surgery and Rehabilitation,Loyola University Medical Center,Maywood,IL,USA4.Department of Orthopaedic Surgery and Rehabilitation,Loyola University Medical Center,Maywood,IL,USA;Alcohol Research Program (ARP),Loyola University Chicago Stritch School of Medicine,Maywood,IL,USA
摘要：Nearly half of orthopaedic trauma patients are intoxicated at the time of injury,and excess alcohol consumption increases the risk for fracture nonunion.Previous studies show alcohol disrupts fracture associated Wnt signaling required for nor-mal bone fracture repair.Intermittent parathyroid hormone (PTH) promotes bone growth through canonical Wnt signaling,however,no studies have investigated the effect of PTH on alcohol-inhibited bone fracture repair.Male C57BL/6 mice received two-3 day alcohol binges separated by 4 days before receiving a mid-shaft tibia frac-ture.Postoperatively,mice received PTH daily until euthanasia.Wnt/β-catenin sign-aling was analyzed at 9 days post-fracture.As previously observed,acute alcohol exposure resulted in a >2-fold decrease in total and the active form of β-catenin and a 2-fold increase in inactive β-catenin within the fracture callus.Intermittent PTH abrogated the effect of alcohol on β-catenin within the fracture callus.Upstream of β-catenin,alcohol-treated animals had a 2-fold decrease in total LRP6,the Wnt co-receptor,which was restored with PTH treatment.Alcohol nor PTH had any sig-nificant effect on GSK-3β.These data show that intermittent PTH following a tibia fracture restores normal expression of Wnt signaling proteins within the fracture callus of alcohol-treated mice.
机标关键词：
论文发表日期：2020-06-25
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：8( 200-207 )
英文信息