CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair
CD169+ macrophages are critical for osteoblast maintenance and promote intramembranous and endochondral ossification during bone repair
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DOI：
10.1016/j.biomaterials.2017.10.033
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发表时间：
2019-03-01
期刊：
影响因子：
14
通讯作者：
Pettit, Allison Robyn
中科院分区：
文献类型：
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作者：
Batoon, Lena;Millard, Susan Marie;Pettit, Allison Robyn
骨巨噬细胞（骨瘤）有助于骨稳态和再生。为了进一步区分破骨细胞的功能，破骨细胞有许多共同的标志物和生长因子的要求，我们开发了一种快速，无酶的骨瘤富集方案，允许通过流式细胞术表征最低限度操作的骨瘤。骨瘤与破骨细胞在Siglec 1（CD 169）的表达方面不同。使用CD 169-白喉毒素（DT）受体（DTR）敲入模型证实了这种区别。DT处理的幼稚CD 169-DTR小鼠导致选择性和惊人的骨瘤损失，而破骨细胞和骨小梁面积不受影响。与先前报道的营养相互作用一致，骨瘤损失伴随着成骨细胞的伴随和成比例的显著减少。在通过膜内（胫骨损伤）或软骨内（股骨内板骨折模型）骨化愈合的两种骨损伤模型中评估CD 169（+）巨噬细胞耗竭的影响。在这两种模型中，CD 169（+）巨噬细胞，包括osteomac耗竭损害骨修复。重要的是，DT治疗CD 169-DTR小鼠不影响破骨细胞的频率在任何一个模型。在股骨骨折模型中，骨痂形成的程度与骨痂内存留的F4/80（+）巨噬细胞数量相关。总之，这些观察结果提供了令人信服的支持，即CD 169（+）骨细胞，独立于破骨细胞，在骨稳态和修复过程中为成骨细胞提供重要的促合成代谢支持。(C)2017爱思唯尔有限公司版权所有
Osteal macrophages (osteomacs) contribute to bone homeostasis and regeneration. To further distinguish their functions from osteoclasts, which share many markers and growth factor requirements, we developed a rapid, enzyme-free osteomac enrichment protocol that permitted characterization of minimally manipulated osteomacs by flow cytometry. Osteomacs differ from osteoclasts in expression of Siglec1 (CD169). This distinction was confirmed using the CD169-diphtheria toxin (DT) receptor (DTR) knock-in model. DT treatment of naive CD169-DTR mice resulted in selective and striking loss of osteomacs, whilst osteoclasts and trabecular bone area were unaffected. Consistent with a previously reported trophic interaction, osteomac loss was accompanied by a concomitant and proportionately striking reduction in osteoblasts. The impact of CD169(+) macrophage depletion was assessed in two models of bone injury that heal via either intramembranous (tibial injury) or endochondral (internally plated femoral fracture model) ossification. In both models, CD169(+) macrophage, including osteomac depletion compromised bone repair. Importantly, DT treatment in CD169-DTR mice did not affect osteoclast frequency in either model. In the femoral fracture model, the magnitude of callus formation correlated with the number of F4/80(+) macrophages that persisted within the callus. Overall these observations provide compelling support that CD169(+) osteomacs, independent of osteoclasts, provide vital pro-anabolic support to osteoblasts during both bone homeostasis and repair. (C) 2017 Elsevier Ltd. All rights reserved.