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Osteoporosis International

Published in:

01-06-2011 | Original Article

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Authors: T. Kobayashi, S. Onodera, E. Kondo, H. Tohyama, H. Fujiki, A. Yokoyama, K. Yasuda

Published in: Osteoporosis International | Issue 6/2011

Abstract

Summary

This study investigated the role of macrophage migration inhibitory factor (MIF) in fracture repair using MIF gene-deficient mice (MIF KO). Fracture healing was delayed in MIF KO, and this was mainly due to the delay in the mineralization of osteoid within the fracture callus.

Introduction

We previously reported that the expression of macrophage migration inhibitory factor (MIF) was up-regulated during the fracture healing process in rats. However, its role in the pathophysiology of this process remained unclear. The aim of the present study was to clarify the role of MIF in the fracture healing process using MIF gene-deficient mice (MIF KO).

Methods

Bone repair in wild-type mice (WT) and MIF KO (n = 70, respectively) was investigated using a tibia fracture model. Radiographic, biomechanical, histological, bone histomorphometric, and molecular analyses were performed.

Results

Post-fracture biomechanical testing showed that maximum load and stiffness were significantly lower in MIF KO than in WT on day 42. However, similar levels were observed between the two groups on day 84. Bone histomorphometric analysis revealed significantly higher osteoid volume, a lower mineral apposition rate, and smaller numbers of osteoclasts in the MIF KO callus compared to the WT callus. The messenger ribonucleic acid expressions of matrix metalloproteinase (MMP)-2, membranous type 1-MMP, cathepsin K, and tissue nonspecific alkaline phosphatase were found to be significantly suppressed in the MIF KO callus.

Conclusion

The results of the present study suggest that delayed fracture healing in MIF KO was mainly attributable to a delay in osteoid mineralization.

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Title: Impaired fracture healing in macrophage migration inhibitory factor-deficient mice
Authors: T. Kobayashi
S. Onodera
E. Kondo
H. Tohyama
H. Fujiki
A. Yokoyama
K. Yasuda
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 6/2011
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-010-1385-0

At a glance: The STEP trials

Springer Medicine

Impaired fracture healing in macrophage migration inhibitory factor-deficient mice

Abstract

Summary

Introduction

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Summary

Introduction

Methods

Results

Conclusion

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