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 Aug 05; 19(8):11628-44.M

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.

Links

Publisher Full Text

ncbi.nlm.nih.gov

mdpi.com

PMC Free PDF

Authors+Show Affiliations

Baek JM

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. phone8418@hanmail.net.

Kim JY

Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. kimjy1014@gmail.com.

Cheon YH

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. hanleuni@naver.com.

Park SH

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. beryls@wku.ac.kr.

Ahn SJ

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. asj0427@naver.com.

Yoon KH

Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. khy1646@wku.ac.kr.

Oh J

Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. jmoh@wku.ac.kr.

Lee MS

Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. ckhlms@wku.ac.kr.

MeSH

Acid PhosphataseAconitumAnimalsBone ResorptionBone and BonesGene Expression RegulationIsoenzymesLipopolysaccharidesMacrophagesMaleMiceNFATC Transcription FactorsOsteoclastsPlant ExtractsProto-Oncogene Proteins c-fosRANK LigandSignal TransductionTartrate-Resistant Acid PhosphataseX-Ray Microtomography

Pub Type(s)

Journal Article

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25100255

Citation

Baek, Jong Min, et al. "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 (Basel, Switzerland), vol. 19, no. 8, 2014, pp. 11628-44.

Baek JM, Kim JY, Cheon YH, et al. 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(8):11628-44.

Baek, J. M., Kim, J. Y., Cheon, Y. H., Park, S. H., Ahn, S. J., Yoon, K. H., Oh, J., & Lee, M. S. (2014). 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 (Basel, Switzerland), 19(8), 11628-44. https://doi.org/10.3390/molecules190811628

Baek JM, et al. 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 Aug 5;19(8):11628-44. PubMed PMID: 25100255.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - 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. AU - Baek,Jong Min, AU - Kim,Ju-Young, AU - Cheon,Yoon-Hee, AU - Park,Sun-Hyang, AU - Ahn,Sung-Jun, AU - Yoon,Kwon-Ha, AU - Oh,Jaemin, AU - Lee,Myeung Su, Y1 - 2014/08/05/ PY - 2014/07/09/received PY - 2014/07/29/revised PY - 2014/07/30/accepted PY - 2014/8/8/entrez PY - 2014/8/8/pubmed PY - 2015/4/1/medline SP - 11628 EP - 44 JF - Molecules (Basel, Switzerland) JO - Molecules VL - 19 IS - 8 N2 - 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. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/25100255/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_ L2 - https://www.mdpi.com/resolver?pii=molecules190811628 DB - PRIME DP - Unbound Medicine ER -

Tags