Alexander Kylie Anne, Raggatt Liza-Jane, Millard Susan, Batoon Lena, Chiu-Ku Wu Andy, Chang Ming-Kang, Hume David Arthur, Pettit Allison Robyn
The University of Queensland, Institute for Molecular Bioscience, St Lucia, Queensland, Australia.
The University of Queensland Centre for Clinical Research, Faculty of Medicine and Biomedical Sciences, Royal Brisbane Hospital, Herston, Queensland, Australia.
Immunol Cell Biol. 2017 Jan;95(1):7-16. doi: 10.1038/icb.2016.74. Epub 2016 Nov 15.
Better understanding of bone growth and regeneration mechanisms within periosteal tissues will improve understanding of bone physiology and pathology. Macrophage contributions to bone biology and repair have been established but specific investigation of periosteal macrophages has not been undertaken. We used an immunohistochemistry approach to characterize macrophages in growing murine bone and within activated periosteum induced in a mouse model of bone injury. Osteal tissue macrophages (osteomacs) and resident macrophages were distributed throughout resting periosteum. In tissues collected from 4-week-old mice, osteomacs were observed intimately associated with sites of periosteal diaphyseal and metaphyseal bone dynamics associated with normal growth. This included F4/80Mac-2 osteomac association with extended tracks of bone formation (modeling) on diphyseal periosteal surfaces. Although this recapitulated endosteal osteomac characteristics, there was subtle variance in the morphology and spatial organization of periosteal modeling-associated osteomacs, which likely reflects the greater structural complexity of periosteum. Osteomacs, resident macrophages and inflammatory macrophages (F4/80Mac-2) were associated with the complex bone dynamics occurring within the periosteum at the metaphyseal corticalization zone. These three macrophage subsets were also present within activated native periosteum after bone injury across a 9-day time course that spanned the inflammatory through remodeling bone healing phases. This included osteomac association with foci of endochondral ossification within the activated native periosteum. These observations confirm that osteomacs are key components of both osteal tissues, in spite of salient differences between endosteal and periosteal structure and that multiple macrophage subsets are involved in periosteal bone dynamics.
更好地了解骨膜组织内的骨生长和再生机制将有助于深化对骨生理学和病理学的认识。巨噬细胞对骨生物学和修复的作用已得到确认，但尚未对骨膜巨噬细胞进行具体研究。我们采用免疫组织化学方法，对生长中的小鼠骨骼以及骨损伤小鼠模型中激活的骨膜内的巨噬细胞进行表征。骨组织巨噬细胞（osteomacs）和驻留巨噬细胞分布于整个静止骨膜。在4周龄小鼠采集的组织中，观察到osteomacs与正常生长相关的骨干和干骺端骨膜骨动态部位密切相关。这包括F4/80Mac-2 osteomac与骨干骨膜表面骨形成（建模）的延伸轨迹相关联。尽管这概括了骨内膜osteomac的特征，但骨膜建模相关osteomacs的形态和空间组织存在细微差异，这可能反映了骨膜更大的结构复杂性。Osteomacs、驻留巨噬细胞和炎性巨噬细胞（F4/80Mac-2）与干骺端皮质化区域骨膜内发生的复杂骨动态相关。在跨越炎症到骨愈合重塑阶段的9天时间进程中，这三种巨噬细胞亚群也存在于骨损伤后激活的天然骨膜内。这包括osteomac与激活的天然骨膜内软骨内成骨灶相关联。这些观察结果证实，尽管骨内膜和骨膜结构存在显著差异，但osteomacs是两种骨组织的关键组成部分，并且多种巨噬细胞亚群参与骨膜骨动态。
