Document Detail

Fracture Healing via Periosteal Callus Formation Requires Macrophages for Both Initiation and Progression of Early Endochondral Ossification.
MedLine Citation:
PMID:  25285719     Owner:  NLM     Status:  Publisher    
The distribution, phenotype, and requirement of macrophages for fracture-associated inflammation and/or early anabolic progression during endochondral callus formation were investigated. A murine femoral fracture model [internally fixed using a flexible plate (MouseFix)] was used to facilitate reproducible fracture reduction. IHC demonstrated that inflammatory macrophages (F4/80(+)Mac-2(+)) were localized with initiating chondrification centers and persisted within granulation tissue at the expanding soft callus front. They were also associated with key events during soft-to-hard callus transition. Resident macrophages (F4/80(+)Mac-2(neg)), including osteal macrophages, predominated in the maturing hard callus. Macrophage Fas-induced apoptosis transgenic mice were used to induce macrophage depletion in vivo in the femoral fracture model. Callus formation was completely abolished when macrophage depletion was initiated at the time of surgery and was significantly reduced when depletion was delayed to coincide with initiation of early anabolic phase. Treatment initiating 5 days after fracture with the pro-macrophage cytokine colony stimulating factor-1 significantly enhanced soft callus formation. The data support that inflammatory macrophages were required for initiation of fracture repair, whereas both inflammatory and resident macrophages promoted anabolic mechanisms during endochondral callus formation. Overall, macrophages make substantive and prolonged contributions to fracture healing and can be targeted as a therapeutic approach for enhancing repair mechanisms. Thus, macrophages represent a viable target for the development of pro-anabolic fracture treatments with a potentially broad therapeutic window.
Liza J Raggatt; Martin E Wullschleger; Kylie A Alexander; Andy C-K Wu; Susan M Millard; Simranpreet Kaur; Michelle L Maugham; Laura S Gregory; Roland Steck; Allison R Pettit
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-3
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-6     Completed Date:  -     Revised Date:  2014-10-7    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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