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学科主题: 临床医学
题名:
A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL
作者: Qian, Hongyan1,2; Yuan, Huihui1; Wang, Jun1,3; Du, Yuxuan1; Zhang, Xulong1; Sun, Ying1; Li, Zhanguo4; Zhao, Wenming1
关键词: Monoclonal antibody ; Tumor necrosis factor-alpha(TNIF-alpha) ; Receptor activator of nuclear factor-kappa B ligand (RANKL) ; Acute inflammation ; Osteoporosis
刊名: INTERNATIONAL IMMUNOPHARMACOLOGY
发表日期: 2014-06-01
DOI: 10.1016/j.intimp.2014.03.017
卷: 20, 期:2, 页:370-376
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Immunology ; Pharmacology & Pharmacy
研究领域[WOS]: Immunology ; Pharmacology & Pharmacy
关键词[WOS]: KAPPA-B LIGAND ; NECROSIS-FACTOR-ALPHA ; INDUCED BONE LOSS ; COLLAGEN-INDUCED ARTHRITIS ; OSTEOCLAST DIFFERENTIATION ; RHEUMATOID-ARTHRITIS ; RECEPTOR ACTIVATOR ; PAW EDEMA ; DENOSUMAB ; MICE
英文摘要:

This study aimed to generate a monoclonal antibody (mAb) targeting both tumor necrosis factor-a (TNF-alpha) and receptor activator of NF-kappa B ligand (RANKL) and to evaluate the therapeutic effects of this antibody on acute inflammation and osteoporosis. We used hybridoma techniques to generate potential mAbs and enzymelinked immunosorbent assay (ELISA) to determine their specificity. Crystal violet staining was performed to measure the effective dose of the candidate mAbs. The neutralizing effect of the mAbs was evaluated by TNF-alpha mediated cytotoxicity and RANKL-induced osteoclastogenesis assays. We further assessed the therapeutic effect of the mAbs in BALB/c mice with carrageenan-induced acute inflammation and ovariectomy-induced osteoporosis. We successfully generated an IgG1 isotype mAb that recognizes human TNF-alpha and RANKL, which we named 8G12. The 50% effective dose of 8G12 was approximately 1 mu g/mL. L929 cells treated with 8G12 exhibited decreased levels of apoptosis (20.04% compared to 63.28% in the positive controls). In addition, treatment with 8G12 inhibited osteoclastogenesis in a dose-dependent manner in vitro. Carrageenan-induced paw edema was significantly reduced in the 8G12-treated mice compared to the positive controls. Treatment with 8G12 also reduced the number of infiltrating leukocytes by more than 50%. The 8G12 treatment not only prevented bone loss but also increased the number, thickness and volume of trabeculae and reduced trabecular separation in ovariectomized mice. Our data suggest that the 8G12 effectively neutralizes the bioactivity of TNF-alpha and RANKL, ameliorating osteoporosis and inflammation. We therefore propose that 8G12 could be a candidate for generating therapeutic antibodies for treating inflammatory bone diseases. (C) 2014 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2010CB529106 ; 31370936
项目资助者: State Key Development Program for Basic Research of China ; National Nature Science Foundation of China
WOS记录号: WOS:000336463800014
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51638
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.Xiamen Univ, Affiliated Hosp 1, Dept Rheumatol & Clin Immunol, Xiamen 361003, Fujian, Peoples R China
3.Inner Mongolia Med Univ, Sch Basic Med Sci, Dept Pathogeny Biol & Immunol, Hohhot 010110, Inner Mongolia, Peoples R China
4.Peking Univ, Peoples Hosp, Clin Immunol Ctr, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China

Recommended Citation:
Qian, Hongyan,Yuan, Huihui,Wang, Jun,et al. A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL[J]. INTERNATIONAL IMMUNOPHARMACOLOGY,2014,20(2):370-376.
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