RANKL-induced M1 macrophages are involved in bone formation.

RANKL-induced M1 macrophages are involved in bone formation.
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DOI:
10.1038/boneres.2017.19
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发表时间:
2017
期刊:
影响因子:
12.7
通讯作者:
Xiao Y
Xiao Y
中科院分区:
医学1区
文献类型:
--
作者:
Huang R;Wang X;Zhou Y;Xiao Y

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M1巨噬细胞的活化可以通过用脂多糖(LPS)和干扰素-γ(IFN-γ)刺激它们来实现。然而,M1可以在没有任何病理刺激的生理条件下被发现。本研究旨在了解RANKL诱导的M1巨噬细胞与病理诱导的巨噬细胞相比参与骨形成。采用Fischer大鼠,观察正常和损伤股骨髁内巨噬细胞的分布。用LPS+IFN-γ和RANKL激活骨髓源性巨噬细胞(BMDM),以实现体外M1激活。通过逆转录-定量聚合酶链反应(RT-qPCR)和荧光激活细胞分选(FACS)测定与炎症、破骨细胞生成、血管生成和迁移相关的基因表达。组织巨噬细胞在不同的骨区域表现出不同的表达模式。在体内发现RANKL与诱导型一氧化氮合酶阳性(iNOS+)细胞非常接近,表明RANKL表达与iNOS+细胞之间存在相关性,尤其是在骨小梁中。与病理诱导的巨噬细胞相比,RANKL诱导的巨噬细胞显示出不同的细胞因子分泌特征。破骨细胞和M1巨噬细胞在骨愈合过程中均在第7天达到峰值。RANKL可激活M1样巨噬细胞,其性质与LPS+IFN-γ诱导的巨噬细胞不同。这些RANKL激活的M1巨噬细胞积极参与骨形成。
The activation of M1 macrophages can be achieved by stimulating them with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). However, M1 can be found under physiological conditions without any pathological stimuli. This study aimed to understand the involvement of RANKL-induced M1 macrophages in bone formation compared with pathologically induced macrophages. Fischer rats were used to investigate macrophage distribution in normal and injured femoral condyles in vivo. Bone marrow-derived macrophages (BMDMs) were activated with LPS+IFN-γ and RANKL to achieve M1 activation in vitro. Gene expression related to inflammation, osteoclastogenesis, angiogenesis, and migration was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and fluorescence-activated cell sorting (FACS). Tissue macrophages showed distinct expression patterns at different bone regions. RANKL was found in close proximity to inducible nitric oxide synthase-positive (iNOS+) cells in vivo, suggesting an association between RANKL expression and iNOS+ cells, especially in trabecular bone. RANKL-induced macrophages showed a different cytokine secretion profile compared with pathologically induced macrophages. Both osteoclasts and M1 macrophages peaked on day 7 during bone healing. RANKL could trigger M1-like macrophages with properties that were different from those of LPS+IFN-γ-induced macrophages. These RANKL-activated M1 macrophages were actively involved in bone formation.
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