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学科主题: 临床医学
题名:
Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
作者: Zhang, Xiaoqing1,2; Liu, Sibo1; Li, Shentao1; Du, Yuxuan1; Dou, Yunpeng1; Li, Zhanguo3; Yuan, Huihui1; Zhao, Wenming1
刊名: BIOMED RESEARCH INTERNATIONAL
发表日期: 2015
DOI: 10.1155/2015/765490
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Medicine, Research & Experimental
研究领域[WOS]: Biotechnology & Applied Microbiology ; Research & Experimental Medicine
关键词[WOS]: RHEUMATOID-ARTHRITIS ; CLINICAL REMISSION ; IN-VIVO ; WNT ; DICKKOPF-1 ; THERAPY
英文摘要:

Dickkopf-1 (DKK1), a secretory inhibitor of canonical Wnt signaling, plays a critical role in certain bone loss diseases. Studies have shown that serum levels of DKK1 are significantly higher in rheumatoid arthritis (RA) patients and are correlated with the severity of the disease, which indicates the possibility that bone erosion in RA may be inhibited by neutralizing the biological activity of DKK1. In this study, we selected a panel of twelve peptides using the software DNASTAR 7.1 and screened high affinity and immunogenicity epitopes in vitro and in vivo assays. Furthermore, we optimized four B cell epitopes to design a novel DKK1 multiepitope DNA vaccine and evaluated its bone protective effects in collagen-induced arthritis (CIA), a mouse model of RA. High level expression of the designed vaccine was measured in supernatant of COS7 cells. In addition, intramuscular immunization of BALB/c mice with this vaccine was also highly expressed and sufficient to induce the production of long-term IgG, which neutralized natural DKK1 in vivo. Importantly, this vaccine significantly attenuated bone erosion in CIA mice compared with positive control mice. These results provide evidence for the development of a DNA vaccine targeted against DKK1 to attenuate bone erosion.

语种: 英语
所属项目编号: 2010CB529106 ; 31400767
项目资助者: State Key Development Program for Basic Research of China ; National Nature Science Foundations of China
WOS记录号: WOS:000354671700001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63040
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Capital Med Univ, Sch Basic Med Sci, Dept Immunol, Beijing 100069, Peoples R China
2.China Med Univ, Coll Med Sci, Dept Immunol, Shenyang 110122, Liaoning, Peoples R China
3.Peking Univ, Peoples Hosp, Clin Immunol Ctr, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China

Recommended Citation:
Zhang, Xiaoqing,Liu, Sibo,Li, Shentao,et al. Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice[J]. BIOMED RESEARCH INTERNATIONAL,2015.
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