Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts.
Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts.
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DOI：
10.1186/ar2046
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发表时间：
2006
影响因子：
4.9
通讯作者：
Miyasaka N
中科院分区：
文献类型：
--
作者：
Komano Y;Nanki T;Hayashida K;Taniguchi K;Miyasaka N
破骨细胞介导的骨吸收增加会导致多种疾病，例如骨质疏松症和类风湿性关节炎（RA）中的骨侵蚀。破骨细胞源自单核细胞/巨噬细胞谱系，但确切的起源仍不清楚。在本研究中，我们发现纯化的 CD16- 人外周血单核细胞亚群（而非 CD16+ 单核细胞亚群）通过 NF-κB 配体受体激活剂 (RANKL) 与巨噬细胞集落刺激因子 (M-CSF) 的联合刺激，分化为破骨细胞。当用 RANKL + M-CSF 刺激时，整合素-β3 mRNA 和整合素-αvβ3 异二聚体仅在 CD16- 单核细胞上表达。通过靶向 β3 的小干扰 RNA 下调 β3 亚基表达，消除了 CD16-单核细胞亚群的破骨细胞生成。相比之下，CD16+单核细胞亚群比CD16-亚群表达更多的肿瘤坏死因子α和IL-6，并且通过RANKL刺激进一步增强。 RA滑膜组织检查显示CD16+和CD16-巨噬细胞聚集。我们的结果表明，外周血单核细胞由两个功能异质的亚群组成，对 RANKL 具有不同的反应。破骨细胞似乎起源于CD16-单核细胞，整合素β3对于破骨细胞生成是必需的。因此，阻断 CD16-单核细胞的积累和激活可能是一种有益的抗骨吸收治疗方法，尤其是对于 RA。
Increased bone resorption mediated by osteoclasts causes various diseases such as osteoporosis and bone erosion in rheumatoid arthritis (RA). Osteoclasts are derived from the monocyte/macrophage lineage, but the precise origin remains unclear. In the present study, we show that the purified CD16- human peripheral blood monocyte subset, but not the CD16+ monocyte subset, differentiates into osteoclast by stimulation with receptor activator of NF-κB ligand (RANKL) in combination with macrophage colony-stimulating factor (M-CSF). Integrin-β3 mRNA and the integrin-αvβ3 heterodimer were only expressed on CD16- monocytes, when they were stimulated with RANKL + M-CSF. Downregulation of β3-subunit expression by small interfering RNA targeting β3 abrogated osteoclastogenesis from the CD16- monocyte subset. In contrast, the CD16+ monocyte subset expressed larger amounts of tumor necrosis factor alpha and IL-6 than the CD16- subset, which was further enhanced by RANKL stimulation. Examination of RA synovial tissue showed accumulation of both CD16+ and CD16- macrophages. Our results suggest that peripheral blood monocytes consist of two functionally heterogeneous subsets with distinct responses to RANKL. Osteoclasts seem to originate from CD16- monocytes, and integrin β3 is necessary for osteoclastogenesis. Blockade of accumulation and activation of CD16- monocytes could therefore be a beneficial approach as an anti-bone resorptive therapy, especially for RA.
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DOI：
10.1186/ar149
发表时间：
2001
期刊：
Arthritis research
影响因子：
--
作者：
Hayashida K;Nanki T;Girschick H;Yavuz S;Ochi T;Lipsky PE
通讯作者：
Lipsky PE
影响因子：
4.8
作者：
Li, XT;Udagawa, N;Takahashi, N
通讯作者：
Takahashi, N
影响因子：
--
作者：
CHU, CQ;FIELD, M;MAINI, RN
通讯作者：
MAINI, RN
影响因子：
15.9
作者：
Engelman, VW;Nickols, GA;Teitelbaum, SL
通讯作者：
Teitelbaum, SL
影响因子：
4.8
作者：
FISHER, JE;CAULFIELD, MP;ROSENBLATT, M
通讯作者：
ROSENBLATT, M