Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.
Interleukin-17A upregulates receptor activator of NF-kappaB on osteoclast precursors.
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DOI：
10.1186/ar2936
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发表时间：
2010
影响因子：
4.9
通讯作者：
Bowman EP
中科院分区：
文献类型：
--
作者：
Adamopoulos IE;Chao CC;Geissler R;Laface D;Blumenschein W;Iwakura Y;McClanahan T;Bowman EP
免疫系统和骨骼系统之间的相互作用从自身免疫性疾病(如类风湿性关节炎)中观察到的骨丢失中得到证明。在本文中，我们描述了免疫细胞因子IL-17A直接影响破骨细胞生成的新机制。从健康供者中分离人CD14+细胞，在牙本质切片和盖片上培养，并用IL-17A和/或核因子受体激活剂κB配体(RANKL)刺激。通过基因表达、流式细胞仪、抗酒石酸酸性磷酸酶染色、荧光和电子显微镜观察破骨细胞分化情况。应用微型计算机断层扫描和血清RANKL/骨保护素浓度研究野生型(Wt)和IL-17A-/-小鼠的生理性骨重建。用分离自IL-17A-/-和Wt小鼠的骨髓巨噬细胞进行功能性破骨细胞生成实验。IL-17A在体外上调人破骨细胞前体上的NF-κB受体激活剂，导致对RANKL信号、破骨细胞分化和骨丢失的敏感性增加。IL-17A-/-小鼠具有与Wt小鼠相似的生理性骨稳态，从这些小鼠分离的骨髓巨噬细胞发育出功能齐全的正常破骨细胞。总的来说，我们的数据表明，抗IL-17A治疗是治疗与自身免疫性疾病相关的骨丢失的选择性治疗靶点。
The interaction between the immune and skeletal systems is evidenced by the bone loss observed in autoimmune diseases such as rheumatoid arthritis. In this paper we describe a new mechanism by which the immune cytokine IL-17A directly affects osteoclastogenesis. Human CD14+ cells were isolated from healthy donors, cultured on dentine slices and coverslips and stimulated with IL-17A and/or receptor activator of NF-κB ligand (RANKL). Osteoclast differentiation was evaluated by gene expression, flow cytometry, tartrate-resistant acid phosphatase staining, fluorescence and electron microscopy. Physiologic bone remodelling was studied in wild-type (Wt) and IL-17A-/- mice using micro-computer tomography and serum RANKL/osteoprotegerin concentration. Functional osteoclastogenesis assays were performed using bone marrow macrophages isolated from IL-17A-/- and Wt mice. IL-17A upregulates the receptor activator for NF-κB receptor on human osteoclast precursors in vitro, leading to increased sensitivity to RANKL signalling, osteoclast differentiation and bone loss. IL-17A-/- mice have physiological bone homeostasis indistinguishable from Wt mice, and bone marrow macrophages isolated from these mice develop fully functional normal osteoclasts. Collectively our data demonstrate anti-IL-17A treatment as a selective therapeutic target for bone loss associated with autoimmune diseases.
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DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
通讯作者：
Suda T
影响因子：
20.3
作者：
Rivollier, A;Mazzorana, M;Servet-Delprat, C
通讯作者：
Servet-Delprat, C
DOI：
10.1016/j.bbrc.2006.09.076
发表时间：
2006-11-17
影响因子：
3.1
作者：
Adamopoulos, Iannis E.;Xia, Zhidao;Athanasou, Nicholas A.
通讯作者：
Athanasou, Nicholas A.
影响因子：
15.3
作者：
Kim, N;Kadono, Y;Choi, Y
通讯作者：
Choi, Y
影响因子：
6.7
作者：
Lubberts, E;Joosten, LAB;van den Berg, WB
通讯作者：
van den Berg, WB