期刊
BONE
卷 106, 期 -, 页码 78-89出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bone.2015.10.019
关键词
Delayed fracture healing; Macrophage depletion; Osteoimmunology; Endochondral ossification; M1 and M2 macrophage phenotype
资金
- Berlin Brandenburg Center for Regenerative Therapies (BCRT)
- DFG [SCHE 1594/SCHM 2977]
- IRI life sciences of the Humboldt-University
- Friede Springer Stiftung
In fracture healing, skeletal and immune system are closely interacting through common cell precursors and molecular mediators. It is thought that the initial inflammatory reaction, which involves migration of macrophages into the fracture area, has a major impact on the long term outcome of bone repair. Interestingly, macrophages reside during all stages of fracture healing. Thus, we hypothesized a critical role for macrophages in the subsequent phases of bone regeneration. This study examined the impact of in vivo induced macrophage reduction; using clodronate liposomes, on the different healing phases of bone repair in a murine model of a standard closed femoral fracture. A reduction in macrophages had no obvious effect on the early fracture healing phase, but resulted in a delayed hard callus formation, thus severely altering endochondral ossification. Clodronate treated animals clearly showed delayed bony consolidation of cartilage and enhanced periosteal bone formation. Therefore, we decided to backtrack macrophage distribution during fracture healing in non-treated mice, focusing on the identification of the M1 and M2 subsets. We observed that M2 macrophages were clearly prevalent during the ossification phase. Therefore enhancement of M2 phenotype in macrophages was investigated as a way to further bone healing. Induction. of M2 macrophages through interleukin 4 and 13 significantly enhanced bone formation during the 3 week investigation period. These cumulative data illustrate their so far unreported highly important role in endochondral ossification and the necessity of a fine balance in M1/M2 macrophage function, which appears mandatory to fracture healing and successful regeneration. (C) 2016 Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据