Macrophages are requisite for angiogenesis of type H vessels during bone regeneration in mice.
Macrophages are requisite for angiogenesis of type H vessels during bone regeneration in mice.
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DOI：
10.1016/j.bone.2021.116200
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发表时间：
2021-09
期刊：
影响因子：
4.1
通讯作者：
Y. Kohara;R. Kitazawa;Ryuma Haraguchi;Yuuki Imai;S. Kitazawa
中科院分区：
文献类型：
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作者：
Y. Kohara;R. Kitazawa;Ryuma Haraguchi;Yuuki Imai;S. Kitazawa
巨噬细胞是破骨细胞的祖细胞，也是骨代谢的调节因子。巨噬细胞不仅在生理条件下介导成骨细胞的骨形成，而且在骨折后也介导骨再生。然而，巨噬细胞调控骨形成和再生的机制仍不清楚。在这里，我们证明了脂质体包封的氯膦酸盐（Clod-lip）注射小鼠模型与由钻孔损伤和吞噬巨噬细胞的有针对性的消耗诱导的皮质骨缺损表现出受损的血管生成的H型血管，耦合血管生成和骨生成。此外，我们还通过RNA-seq分析鉴定了Tgfbi（编码TGFBI）、Plau（编码uPA）和Tgfb 1（编码TGF-β1）为巨噬细胞分泌的介导血管生成和创伤愈合的因子的基因。通过qRT-PCR测定，相关mRNA在骨细胞中的骨髓源性巨噬细胞中高度表达。最后，我们公开了用uPA抑制剂或TGF-β受体I、受体II抑制剂治疗损伤后的骨再生，证实了uPA和TGF-β1在骨再生过程中的重要性。我们的研究结果揭示了一种新的机制，骨再生介导的巨噬细胞。
Macrophages are progenitors of osteoclasts as well as regulators of bone metabolism. Macrophages mediate not only bone formation by osteoblasts under physiological conditions, but also bone regeneration after fracture. The mechanisms of macrophages regulation of bone formation and regeneration remain unclear, however. Here, we demonstrate that the liposome-encapsulated Clodronate (Clod-lip) injected mouse model with cortical bone defect induced by drill-hole injury and targeted depletion of phagocytic macrophages exhibits impaired angiogenesis of type H vessels that couple angiogenesis and osteogenesis. Moreover, we identifyTgfbi(encoding TGFBI),Plau(encoding uPA) andTgfb1(encoding TGF-β1), through RNA-seq analysis, as genes of macrophage-secreted factors mediating angiogenesis and wound healing. The relevant mRNA was highly expressed in bone marrow-derived macrophages among bone cells, as determined through qRT-PCR. Finally, we disclose that treatment with uPA inhibitor or TGF-β receptor I, receptor II inhibitor impairs bone regeneration after injury, confirming the importance of uPA and TGF-β1 during bone regeneration. Our findings reveal a novel mechanism of bone regeneration mediated by macrophages.