Yahara Yasuhito, Ma Xinyi, Gracia Liam, Alman Benjamin A
Department of Orthopaedic Surgery, Duke University School of Medicine, Durham, NC, United States.
Department of Orthopaedic Surgery, Faculty of Medicine, University of Toyama, Toyama, Japan.
Front Cell Dev Biol. 2021 Feb 4;9:622035. doi: 10.3389/fcell.2021.622035. eCollection 2021.
A third of the population sustains a bone fracture, and the pace of fracture healing slows with age. The slower pace of repair is responsible for the increased morbidity in older individuals who sustain a fracture. Bone healing progresses through overlapping phases, initiated by cells of the monocyte/macrophage lineage. The repair process ends with remodeling. This last phase is controlled by osteoclasts, which are bone-specific multinucleated cells also of the monocyte/macrophage lineage. The slower rate of healing in aging can be rejuvenated by macrophages from young animals, and secreted proteins from macrophage regulate undifferentiated mesenchymal cells to become bone-forming osteoblasts. Macrophages can derive from fetal erythromyeloid progenitors or from adult hematopoietic progenitors. Recent studies show that fetal erythromyeloid progenitors are responsible for the osteoclasts that form the space in bone for hematopoiesis and the fetal osteoclast precursors reside in the spleen postnatally, traveling through the blood to participate in fracture repair. Differences in secreted proteins between macrophages from old and young animals regulate the efficiency of osteoblast differentiation from undifferentiated mesenchymal precursor cells. Interestingly, during the remodeling phase osteoclasts can form from the fusion between monocyte/macrophage lineage cells from the fetal and postnatal precursor populations. Data from single cell RNA sequencing identifies specific markers for populations derived from the different precursor populations, a finding that can be used in future studies. Here, we review the diversity of macrophages and osteoclasts, and discuss recent finding about their developmental origin and functions, which provides novel insights into their roles in bone homeostasis and repair.
三分之一的人口会发生骨折，并且骨折愈合的速度会随着年龄增长而减慢。愈合速度减慢是导致骨折的老年个体发病率增加的原因。骨愈合通过重叠的阶段进行，由单核细胞/巨噬细胞谱系的细胞启动。修复过程以重塑结束。最后这个阶段由破骨细胞控制，破骨细胞是同样来自单核细胞/巨噬细胞谱系的骨特异性多核细胞。衰老过程中较慢的愈合速度可以通过幼龄动物的巨噬细胞恢复活力，并且巨噬细胞分泌的蛋白质可调节未分化的间充质细胞成为形成骨的成骨细胞。巨噬细胞可以来源于胎儿红髓祖细胞或成体造血祖细胞。最近的研究表明，胎儿红髓祖细胞负责形成骨髓造血空间的破骨细胞，并且胎儿破骨细胞前体在出生后存在于脾脏中，通过血液流动参与骨折修复。老年和幼年动物巨噬细胞分泌蛋白质的差异调节了未分化间充质前体细胞向成骨细胞分化的效率。有趣的是，在重塑阶段，破骨细胞可以由来自胎儿和出生后前体群体的单核细胞/巨噬细胞谱系细胞融合形成。单细胞RNA测序数据确定了来自不同前体群体的细胞群的特异性标志物，这一发现可用于未来的研究。在这里，我们综述了巨噬细胞和破骨细胞的多样性，并讨论了关于它们的发育起源和功能的最新发现，这为它们在骨稳态和修复中的作用提供了新的见解。
