Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice

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 t...

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Main Authors:	Zhang, Xiaoqing, Liu, Sibo, Li, Shentao, Du, Yuxuan, Dou, Yunpeng, Li, Zhanguo, Yuan, Huihui, Zhao, Wenming
Format:	Online
Language:	English
Published:	Hindawi Publishing Corporation 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436448/

id	pubmed-4436448
recordtype	oai_dc
spelling	pubmed-44364482015-06-14 Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice Zhang, Xiaoqing Liu, Sibo Li, Shentao Du, Yuxuan Dou, Yunpeng Li, Zhanguo Yuan, Huihui Zhao, Wenming Research Article 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. Hindawi Publishing Corporation 2015 2015-05-05 /pmc/articles/PMC4436448/ /pubmed/26075259 http://dx.doi.org/10.1155/2015/765490 Text en Copyright © 2015 Xiaoqing Zhang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhang, Xiaoqing Liu, Sibo Li, Shentao Du, Yuxuan Dou, Yunpeng Li, Zhanguo Yuan, Huihui Zhao, Wenming
spellingShingle	Zhang, Xiaoqing Liu, Sibo Li, Shentao Du, Yuxuan Dou, Yunpeng Li, Zhanguo Yuan, Huihui Zhao, Wenming Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
author_facet	Zhang, Xiaoqing Liu, Sibo Li, Shentao Du, Yuxuan Dou, Yunpeng Li, Zhanguo Yuan, Huihui Zhao, Wenming
author_sort	Zhang, Xiaoqing
title	Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
title_short	Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
title_full	Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
title_fullStr	Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
title_full_unstemmed	Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice
title_sort	designation of a novel dkk1 multiepitope dna vaccine and inhibition of bone loss in collagen-induced arthritic mice
description	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.
publisher	Hindawi Publishing Corporation
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436448/
_version_	1613225244533719040

Designation of a Novel DKK1 Multiepitope DNA Vaccine and Inhibition of Bone Loss in Collagen-Induced Arthritic Mice

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