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Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes local bone erosion and systemic osteoporosis. Harpagoside (HAR), an iridoid glycoside, has various pharmacological effects on pain, arthritis, and inflammation. Our previous study suggests that HAR is more...

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Autores principales: Kim, Ju-Young, Cheon, Yoon-Hee, Ahn, Sung-Jun, Kwak, Sung Chul, Chung, Chong Hyuk, Lee, Chang Hoon, Lee, Myeung Su
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364518/
https://www.ncbi.nlm.nih.gov/pubmed/35948905
http://dx.doi.org/10.1186/s12906-022-03694-y
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author Kim, Ju-Young
Cheon, Yoon-Hee
Ahn, Sung-Jun
Kwak, Sung Chul
Chung, Chong Hyuk
Lee, Chang Hoon
Lee, Myeung Su
author_facet Kim, Ju-Young
Cheon, Yoon-Hee
Ahn, Sung-Jun
Kwak, Sung Chul
Chung, Chong Hyuk
Lee, Chang Hoon
Lee, Myeung Su
author_sort Kim, Ju-Young
collection PubMed
description BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes local bone erosion and systemic osteoporosis. Harpagoside (HAR), an iridoid glycoside, has various pharmacological effects on pain, arthritis, and inflammation. Our previous study suggests that HAR is more deeply involved in the mechanism of bone loss caused by inflammatory stimuli than hormonal changes. Here, we identified the local and systemic bone loss inhibitory effects of HAR on RA and its intracellular mechanisms using a type 2 collagen-induced arthritis (CIA) mouse model. METHODS: The anti-osteoporosis and anti-arthritic effects of HAR were evaluated on bone marrow macrophage in vitro and CIA in mice in vivo by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, micro-CT and histopathological assessments, and cell-based assay. RESULTS: HAR markedly reduced the clinical score and incidence rate of CIA in both the prevention and therapy groups. Histological analysis demonstrated that HAR locally ameliorated the destruction of bone and cartilage and the formation of pannus. In this process, HAR decreased the expression of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in the serum of CIA mice. Additionally, HAR downregulated the expression of receptor activator of nuclear factor-κB ligand and upregulated that of osteoprotegerin. HAR suppressed systemic bone loss by inhibiting osteoclast differentiation and osteoclast marker gene expression in a CIA mouse model. CONCLUSIONS: Taken together, these findings show the beneficial effect of HAR on local symptoms and systemic bone erosion triggered by inflammatory arthritis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03694-y.
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spelling pubmed-93645182022-08-11 Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice Kim, Ju-Young Cheon, Yoon-Hee Ahn, Sung-Jun Kwak, Sung Chul Chung, Chong Hyuk Lee, Chang Hoon Lee, Myeung Su BMC Complement Med Ther Research BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes local bone erosion and systemic osteoporosis. Harpagoside (HAR), an iridoid glycoside, has various pharmacological effects on pain, arthritis, and inflammation. Our previous study suggests that HAR is more deeply involved in the mechanism of bone loss caused by inflammatory stimuli than hormonal changes. Here, we identified the local and systemic bone loss inhibitory effects of HAR on RA and its intracellular mechanisms using a type 2 collagen-induced arthritis (CIA) mouse model. METHODS: The anti-osteoporosis and anti-arthritic effects of HAR were evaluated on bone marrow macrophage in vitro and CIA in mice in vivo by obtaining clinical scores, measuring hind paw thickness and inflammatory cytokine levels, micro-CT and histopathological assessments, and cell-based assay. RESULTS: HAR markedly reduced the clinical score and incidence rate of CIA in both the prevention and therapy groups. Histological analysis demonstrated that HAR locally ameliorated the destruction of bone and cartilage and the formation of pannus. In this process, HAR decreased the expression of inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-6, and IL-1β in the serum of CIA mice. Additionally, HAR downregulated the expression of receptor activator of nuclear factor-κB ligand and upregulated that of osteoprotegerin. HAR suppressed systemic bone loss by inhibiting osteoclast differentiation and osteoclast marker gene expression in a CIA mouse model. CONCLUSIONS: Taken together, these findings show the beneficial effect of HAR on local symptoms and systemic bone erosion triggered by inflammatory arthritis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12906-022-03694-y. BioMed Central 2022-08-10 /pmc/articles/PMC9364518/ /pubmed/35948905 http://dx.doi.org/10.1186/s12906-022-03694-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kim, Ju-Young
Cheon, Yoon-Hee
Ahn, Sung-Jun
Kwak, Sung Chul
Chung, Chong Hyuk
Lee, Chang Hoon
Lee, Myeung Su
Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title_full Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title_fullStr Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title_full_unstemmed Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title_short Harpagoside attenuates local bone Erosion and systemic osteoporosis in collagen-induced arthritis in mice
title_sort harpagoside attenuates local bone erosion and systemic osteoporosis in collagen-induced arthritis in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364518/
https://www.ncbi.nlm.nih.gov/pubmed/35948905
http://dx.doi.org/10.1186/s12906-022-03694-y
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