title: 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.
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.
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. phone8418@hanmail.net.
authors.forename: Jong Min
authors.initials: JM
authors.lastname: Baek
authors.affiliation: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. kimjy1014@gmail.com.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. hanleuni@naver.com.
authors.forename: Yoon-Hee
authors.initials: YH
authors.lastname: Cheon
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. beryls@wku.ac.kr.
authors.forename: Sun-Hyang
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. asj0427@naver.com.
authors.forename: Sung-Jun
authors.initials: SJ
authors.lastname: Ahn
authors.affiliation: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. khy1646@wku.ac.kr.
authors.forename: Kwon-Ha
authors.initials: KH
authors.lastname: Yoon
authors.affiliation: Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. jmoh@wku.ac.kr.
authors.forename: Jaemin
authors.initials: J
authors.lastname: Oh
authors.affiliation: Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. ckhlms@wku.ac.kr.
authors.forename: Myeung Su
authors.initials: MS
authors.lastname: Lee
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D031841:Aconitum / Q000737:chemistry*; D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000071681:Tartrate-Resistant Acid Phosphatase; D055114:X-Ray Microtomography
chemical_list: D007527:Isoenzymes; D008070:Lipopolysaccharides; D050778:NFATC Transcription Factors; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase
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