Bifurcation of osteoclasts and dendritic cells from common progenitors
Bifurcation of osteoclasts and dendritic cells from common progenitors
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DOI：
10.1182/blood.v98.8.2544
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发表时间：
2001-10-15
期刊：
影响因子：
20.3
通讯作者：
Suda, T
中科院分区：
文献类型：
--
作者：
Miyamoto, T;Ohneda, O;Suda, T
破骨细胞和树突状细胞来源于单核细胞/巨噬细胞前体细胞;然而，它们的谱系定型是如何调节的尚不清楚。本研究从单细胞水平探讨了破骨细胞和树突状细胞从共同的前体细胞分化的途径。由巨噬细胞集落刺激因子（M-CSF）和核因子-κ B配体（RANKL）或肿瘤坏死因子-α（TNF-α）的受体激活剂诱导的破骨细胞生成在分化早期通过添加粒细胞-巨噬细胞集落刺激因子（GM-CSF）或白细胞介素-3完全抑制。GM-CSF处理的细胞表达c-Fms和RANK以及低水平的CD 11 c和DEC 205，这在树突状细胞上检测到。添加GM-CSF还降低c-Fos和Fra-1的表达，这是抑制破骨细胞生成的重要事件。在转基因小鼠中通过逆转录病毒感染或诱导过表达c-Fos可以挽救破骨细胞分化的失败，即使在GM-CSF的存在下。相比之下，分化成树突状细胞被M-CSF抑制，表明M-CSF和GMCSF共同调节两种谱系的分化。当c-Fos在分化的早期阶段表达时，树突状细胞成熟也被抑制。总之，这些发现表明，c-Fos是破骨细胞和树突状细胞之间的谱系承诺的关键调解人。GM-CSF治疗后破骨细胞祖细胞的谱系确定通过调节c-Fos表达发挥作用。（血。2001;98：2544-2554）（C）2001由美国血液学学会。
Osteoclasts and dendritic cells are derived from monocyte/macrophage precursor cells; however, how their lineage commitment is regulated is unknown. This study investigated the differentiation pathways of osteoclasts and dendritic cells from common precursor cells at the single-cell level. Osteoclastogenesis induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappaB ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha) is completely inhibited by addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 at early stages of differentiation. GM-CSF-treated cells express both c-Fms and RANK and also low levels of CD11c and DEC205, which are detected on dendritic cells. Addition of GM-CSF also reduces expression of both c-Fos and Fra-1, which is an important event for inhibition of osteoclastogenesis. Overexpression of c-Fos by retroviral infection or induction in transgenic mice can rescue a failure in osteoclast differentiation even in the presence of GM-CSF. By contrast, differentiation into dendritic cells is inhibited by M-CSF, indicating that M-CSF and GMCSF reciprocally regulate the differentiation of both lineages. Dendritic cell maturation is also inhibited when c-Fos is expressed at an early stage of differentiation. Taken together, these findings suggest that c-Fos is a key mediator of the lineage commitment between osteoclasts and dendritic cells. The lineage determination of osteoclast progenitors seen following GM-CSF treatment functions through the regulation of c-Fos expression. (Blood. 2001;98:2544-2554) (C) 2001 by The American Society of Hematology.