A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL

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	A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL
	Qian, Hongyan ; Yuan, Huihui ; Wang, Jun ; Du, Yuxuan ; Zhang, Xulong ; Sun, Ying ; Li, Zhanguo ; Zhao, Wenming ; Wang J(王军)
刊名	http://dx.doi.org/10.1016/j.intimp.2014.03.017
	2014
关键词	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	State Key Development Program for Basic Research of China [2010CB529106]; National Nature Science Foundation of China [31370936]; 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
出版者	ELSEVIER SCIENCE BV
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/93606]
专题	医学院－已发表论文
推荐引用方式 GB/T 7714	Qian, Hongyan,Yuan, Huihui,Wang, Jun,et al. A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL[J]. http://dx.doi.org/10.1016/j.intimp.2014.03.017,2014.
APA	Qian, Hongyan.,Yuan, Huihui.,Wang, Jun.,Du, Yuxuan.,Zhang, Xulong.,...&王军.(2014).A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL.http://dx.doi.org/10.1016/j.intimp.2014.03.017.
MLA	Qian, Hongyan,et al."A monoclonal antibody ameliorates local inflammation and osteoporosis by targeting TNF-alpha and RANKL".http://dx.doi.org/10.1016/j.intimp.2014.03.017 (2014).