Macrophages in bone fracture healing: Their essential role in endochondral ossification
Macrophages in bone fracture healing: Their essential role in endochondral ossification
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DOI：
10.1016/j.bone.2015.10.019
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发表时间：
2018-01-01
期刊：
影响因子：
4.1
通讯作者：
Schmidt-Bleek, Katharina
中科院分区：
文献类型：
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作者：
Schlundt, Claudia;El Khassawna, Thaqif;Schmidt-Bleek, Katharina
在骨折愈合过程中，骨骼和免疫系统通过共同的细胞前体和分子介质密切相互作用。据认为，最初的炎症反应，其中涉及迁移到骨折区的巨噬细胞，有一个重大影响的长期结果的骨修复。有趣的是，巨噬细胞存在于骨折愈合的所有阶段。因此，我们假设巨噬细胞在骨再生的后续阶段的关键作用。本研究探讨了体内诱导的巨噬细胞减少的影响;使用氯膦酸盐脂质体，在一个标准的闭合性股骨骨折的小鼠模型的骨修复的不同愈合阶段。巨噬细胞的减少对早期骨折愈合阶段没有明显影响，但导致硬骨痂形成延迟，从而严重改变了软骨内骨化。氯膦酸盐治疗的动物清楚地显示出软骨的延迟骨巩固和增强的骨膜骨形成。因此，我们决定回溯未治疗小鼠骨折愈合过程中巨噬细胞的分布，重点是M1和M2亚群的鉴定。我们观察到M2巨噬细胞在骨化阶段明显流行。因此，研究了巨噬细胞中M2表型的增强作为进一步骨愈合的一种方式。入职。M2巨噬细胞通过白细胞介素4和13显著增强骨形成在3周的研究期间。这些累积的数据说明了它们在软骨内骨化中迄今未报道的高度重要作用以及M1/M2巨噬细胞功能精细平衡的必要性，这似乎是骨折愈合和成功再生的必要条件。(C)2016由Elsevier Inc.出版
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.