MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.
MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha.
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MyD88 而不是 TRIF 对于脂多糖、二酰基脂肽和 IL-1α 诱导的破骨细胞生成至关重要。
DOI：
10.1084/jem.20040689
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发表时间：
2004-09-06
影响因子：
15.3
通讯作者：
Udagawa, N
中科院分区：
文献类型：
--
作者：
Sato, N;Takahashi, N;Suda, K;Nakamura, M;Yimaki, M;Ninomiya, T;Kobayashi, Y;Takada, H;Shibata, K;Yamamoto, M;Takeda, K;Akira, S;Noguchi, T;Udagawa, N
髓样分化因子88（MyD 88）在Toll/白细胞介素（IL）-1受体家族的信号传导中起重要作用。含有Toll-IL-1受体结构域的衔接子诱导干扰素-β（TRIF）介导的信号参与脂多糖（LPS）诱导的MyD 88非依赖性途径。使用MyD 88缺陷（MyD 88-/-）小鼠和TRIF缺陷（TRIF-/-）小鼠，我们研究了MyD 88和TRIF在破骨细胞分化和功能中的作用。LPS、二酰基脂肽和IL-1α刺激TRIF−/−小鼠成骨细胞和造血细胞共培养物中的破骨细胞生成，但不刺激MyD 88 −/−小鼠。这些因子刺激TRIF−/−成骨细胞中的核因子-κB配体mRNA表达的受体激活因子，但不刺激MyD 88 −/−成骨细胞。LPS刺激TRIF−/−成骨细胞产生IL-6，但不刺激TRIF−/−巨噬细胞。LPS和IL-1α增强TRIF−/−破骨细胞的存活，但不增强MyD 88 −/−破骨细胞的存活。由于破骨细胞缺乏Toll样受体（TLR）6，二酰基脂肽不能支持破骨细胞的存活。巨噬细胞同时表达TRIF和TRIF相关的衔接分子（TRAM）mRNA，而成骨细胞和破骨细胞仅表达TRIF mRNA。骨组织形态计量学显示，MyD 88 −/−小鼠表现出骨量减少，骨吸收和骨形成减少。这些结果表明，MyD 88介导的信号是必不可少的破骨细胞的生成和功能诱导的IL-1和TLR配体，MyD 88是生理上参与骨转换。
Myeloid differentiation factor 88 (MyD88) plays essential roles in the signaling of the Toll/interleukin (IL)-1 receptor family. Toll–IL-1 receptor domain-containing adaptor inducing interferon-β (TRIF)-mediated signals are involved in lipopolysaccharide (LPS)-induced MyD88-independent pathways. Using MyD88-deficient (MyD88−/−) mice and TRIF-deficient (TRIF−/−) mice, we examined roles of MyD88 and TRIF in osteoclast differentiation and function. LPS, diacyl lipopeptide, and IL-1α stimulated osteoclastogenesis in cocultures of osteoblasts and hemopoietic cells obtained from TRIF−/− mice, but not MyD88−/− mice. These factors stimulated receptor activator of nuclear factor-κB ligand mRNA expression in TRIF−/− osteoblasts, but not MyD88−/− osteoblasts. LPS stimulated IL-6 production in TRIF−/− osteoblasts, but not TRIF−/− macrophages. LPS and IL-1α enhanced the survival of TRIF−/− osteoclasts, but not MyD88−/− osteoclasts. Diacyl lipopeptide did not support the survival of osteoclasts because of the lack of Toll-like receptor (TLR)6 in osteoclasts. Macrophages expressed both TRIF and TRIF-related adaptor molecule (TRAM) mRNA, whereas osteoblasts and osteoclasts expressed only TRIF mRNA. Bone histomorphometry showed that MyD88−/− mice exhibited osteopenia with reduced bone resorption and formation. These results suggest that the MyD88-mediated signal is essential for the osteoclastogenesis and function induced by IL-1 and TLR ligands, and that MyD88 is physiologically involved in bone turnover.
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通讯作者：
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