Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto, Ontario, Canada.
Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
J Bone Miner Res. 2015 Jun;30(6):1090-102. doi: 10.1002/jbmr.2422.
Macrophages are activated in inflammation and during early phases of repair processes. Interestingly, they are also present in bone during development, but their function during this process is unclear. Here, we explore the function of macrophages in bone development, growth, and repair using transgenic mice to constitutively or conditionally deplete macrophages. Depletion of macrophages led to early skeletal growth retardation and progressive osteoporosis. By 3 months of age, macrophage-deficient mice displayed a 25% reduction in bone mineral density and a 70% reduction in the number of trabecular bone compared to control littermates. Despite depletion of macrophages, functional osteoclasts were still present in bones, lining trabecular bone and the endosteal surface of the cortical bone. Furthermore, ablation of macrophages led to a 60% reduction in the number of bone marrow mesenchymal progenitor cells and a decrease in the ability of these cells to differentiate to osteoblasts. When macrophages were depleted during fracture repair, bone union was impaired. Calluses from macrophage-deficient animals were smaller, and contained less bone and more fibrotic tissue deposition. Taken together, this shows that macrophages are crucial for maintaining bone homeostasis and promoting fracture repair by enhancing the differentiation of mesenchymal progenitors.
巨噬细胞在炎症和修复过程的早期被激活。有趣的是，它们在骨骼发育过程中也存在，但它们在此过程中的功能尚不清楚。在这里，我们使用转基因小鼠来持续或条件性地耗尽巨噬细胞，以探索巨噬细胞在骨骼发育、生长和修复中的功能。巨噬细胞的耗竭导致早期骨骼生长迟缓，并逐渐发展为骨质疏松症。到 3 个月大时，与对照组相比，巨噬细胞缺陷小鼠的骨密度降低了 25%，小梁骨数量减少了 70%。尽管耗尽了巨噬细胞，但骨骼中仍存在功能正常的破骨细胞，这些细胞排列在小梁骨和皮质骨的内骨表面。此外，巨噬细胞的耗竭导致骨髓间充质祖细胞数量减少 60%，并且这些细胞向成骨细胞分化的能力降低。在骨折修复过程中耗尽巨噬细胞时，骨愈合受到损害。来自巨噬细胞缺陷动物的骨痂较小，含有较少的骨和更多的纤维组织沉积。总之，这些结果表明巨噬细胞对于维持骨骼内稳态和促进骨折修复至关重要，其作用是通过增强间充质祖细胞的分化来实现的。
