The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins
The inhibitory effect of interleukin-10 on mouse osteoclast formation involves novel tyrosine-phosphorylated proteins
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DOI：
10.1359/jbmr.2000.15.5.911
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发表时间：
2000-05-01
影响因子：
6.2
通讯作者：
Pike, JW
中科院分区：
文献类型：
--
作者：
Hong, MH;Williams, H;Pike, JW
白细胞介素-10（IL-10）可抑制大鼠和小鼠体内破骨细胞（OC）的形成，但其抑制作用的机制尚不清楚。本研究利用小鼠骨髓细胞与原代成骨细胞（POB）共培养系统，对IL-10的潜在靶细胞及IL-10活化途径的组分进行了研究。IL-10处理以剂量依赖的方式消除OC分化，这种抑制作用与细胞增殖和分化的阶段无关，表明IL-10可能作用于参与OC形成的多种基因，IL-10特异性地消除了富集的骨髓来源的单核细胞（BMM）而不是成骨细胞产生IL-6，IL-10处理还刺激BMM中的蛋白质与IL-10反应元件的结合，而在成骨细胞中没有诱导这种激活。另一种抑制因子（IFN-γ）刺激酪氨酸磷酸化蛋白与单核细胞和成骨细胞中的IL-10反应元件结合，这些数据表明BMM是IL-10作用的直接靶点，重要的是，白细胞介素特异性沉淀证实IL-10处理强烈增加BMM中88、85和70 kDa酪氨酸磷酸化蛋白。总之，这些数据表明IL-10通过直接作用于造血OC前体抑制小鼠OC形成，通过一种新的信号转导和激活途径。
Interleukin-10 (IL-10) inhibits osteoclast (OC) formation in rat and mouse systems, However, little is known concerning the mechanism of this inhibitory effect, Using a coculture system of mouse bone marrow cells and primary osteoblastic cells (POB), we evaluated the potential target cells for IL-IO and components of the IL-10 activating pathway, In the coculture system, IL-10 treatment abolished OC differentiation in a dose-dependent manner, This inhibitory effect occurred regardless of the stage of cellular proliferation and differentiation, suggesting that IL-10 may act on a variety of genes participating in OC formation, IL-10 specifically abrogated the production of IL-6 by enriched bone marrow-derived mononuclear cells (BMM) but not by osteoblastic cells, IL-10 treatment also stimulated the binding of a protein in the BMM to an IL-10 response element, whereas no such activation was induced in osteoblastic cells, In contrast, interferon gamma (IFN-gamma), another inhibitory factor, stimulated tyrosine-phosphorylated proteins to bind to an IL-10 response element in both monocytes and osteoblastic cells, These data suggest that the BMM are the direct target of IL-10 action, Importantly, oligonucleotide-specific precipitation confirmed that IL-10 treatment strongly augmented 88, 85, and 70 kDa tyrosine-phosphorylated proteins in BMM, Taken together, these data show that IL-10 inhibits mouse OC formation by acting directly on hemopoietic OC precursor, through a novel signal transduction and activation pathway.