Osteal Macrophages Promote In Vivo Intramembranous Bone Healing in a Mouse Tibial Injury Model
Osteal Macrophages Promote In Vivo Intramembranous Bone Healing in a Mouse Tibial Injury Model
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DOI：
10.1002/jbmr.354
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发表时间：
2011-07-01
影响因子：
6.2
通讯作者：
Pettit, Allison R.
中科院分区：
文献类型：
--
作者：
Alexander, Kylie A.;Chang, Ming K.;Pettit, Allison R.
骨衬组织含有一群称为骨瘤的常驻巨噬细胞，它们在体内与成骨细胞相互作用并在体外控制矿化。使用小鼠胫骨损伤模型研究了骨瘤在骨修复中的作用，该模型主要通过膜内骨化愈合，并在稳定性骨折修复的所有主要阶段进展。免疫组织化学研究显示，至少两种巨噬细胞群，F4/80（+）Mac-2（-/低）TRACP（-）骨瘤和F4/80（+）Mac-2（hi）TRACP（-）炎性巨噬细胞，存在于骨损伤部位，并持续整个愈合时间过程。通过定量免疫组织学和显微计算机断层扫描评估，在胫骨损伤模型中，骨瘤细胞/巨噬细胞（使用Mafia转基因小鼠模型或氯膦酸盐脂质体递送）或破骨细胞（重组骨保护素治疗）的体内消耗确定了骨瘤细胞是1型胶原（+）（CT 1（+））基质沉积和骨矿化所必需的。相反，给予巨噬细胞生长因子集落刺激因子1（CSF-1）显著增加了损伤部位的骨瘤/巨噬细胞数量，同时增加了新的CT 1（+）基质沉积和矿化。本研究确立了骨瘤作为膜内骨愈合的参与者和作为主要合成代谢骨治疗的靶点。(C)2011年美国骨与矿物质研究学会。
Bone-lining tissues contain a population of resident macrophages termed osteomacs that interact with osteoblasts in vivo and control mineralization in vitro. The role of osteomacs in bone repair was investigated using a mouse tibial bone injury model that heals primarily through intramembranous ossification and progresses through all major phases of stabilized fracture repair. Immunohistochemical studies revealed that at least two macrophage populations, F4/80(+)Mac-2(-/low)TRACP(-) osteomacs and F4/80(+)Mac-2(hi)TRACP(-) inflammatory macrophages, were present within the bone injury site and persisted throughout the healing time course. In vivo depletion of osteomacs/macrophages (either using the Mafia transgenic mouse model or clodronate liposome delivery) or osteoclasts (recombinant osteoprotegerin treatment) established that osteomacs were required for deposition of collagen type 1(+) (CT1(+)) matrix and bone mineralization in the tibial injury model, as assessed by quantitative immunohistology and micro-computed tomography. Conversely, administration of the macrophage growth factor colony-stimulating factor 1 (CSF-1) increased the number of osteomacs/macrophages at the injury site significantly with a concurrent increase in new CT1(+) matrix deposition and enhanced mineralization. This study establishes osteomacs as participants in intramembranous bone healing and as targets for primary anabolic bone therapies. (C) 2011 American Society for Bone and Mineral Research.