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Molecules 2014, 19(8), 11628-11644; doi:10.3390/molecules190811628

Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice

1,2,†
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3,†
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1,2
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1,2
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1,2
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3,4
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1,2,3,5,* and 3,5,6,*
1
Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
2
BK21plus Program & Department of Smart Life-Care Convergence, Graduate School, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
3
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
4
Department of Radiology, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
5
Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
6
Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 9 July 2014 / Revised: 29 July 2014 / Accepted: 30 July 2014 / Published: 5 August 2014
(This article belongs to the Section Natural Products)
View Full-Text   |   Download PDF [3539 KB, uploaded 5 August 2014]   |  

Abstract

Aconitum pseudo-laeve var. erectum (APE) has been widely shown in herbal medicine to have a therapeutic effect on inflammatory conditions. However, there has been no evidence on whether the extract of APE is involved in the biological bone metabolism process, particularly osteoclast-mediated bone resorption. In this study, we confirmed that the administration of APE could restore normal skeletal conditions in a murine model of lipopolysaccharide (LPS)-induced bone loss via a decrease in the receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) ratio and osteoclast number. We then investigated the effect of APE on the RANKL-induced formation and function of osteoclasts to elucidate its underlying molecular mechanisms. APE suppressed the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells, as well as the bone-resorbing activity of mature osteoclasts. Furthermore, APE attenuated nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos without affecting any early signal pathway of osteoclastogenesis. Subsequently, APE significantly downregulated the expression of various genes exclusively expressed in osteoclasts. These results demonstrate that APE restores LPS-induced bone loss through a decrease of the serum RANKL/OPG ratio, and inhibits osteoclast differentiation and function, suggesting the promise of APE as a potential cure for various osteoclast-associated bone diseases. View Full-Text
Keywords: Aconitum pseudo-laeve var. erectum; osteoclast; bone; osteoporosis Aconitum pseudo-laeve var. erectum; osteoclast; bone; osteoporosis
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This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Baek, J.M.; Kim, J.-Y.; Cheon, Y.-H.; Park, S.-H.; Ahn, S.-J.; Yoon, K.-H.; Oh, J.; Lee, M.S. Aconitum pseudo-laeve var. erectum Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand-Induced Osteoclastogenesis via the c-Fos/nuclear Factor of Activated T-Cells, Cytoplasmic 1 Signaling Pathway and Prevents Lipopolysaccharide-Induced Bone Loss in Mice. Molecules 2014, 19, 11628-11644.

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