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Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis

BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs...

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Autores principales: Yin, Mengxing, Zhou, Dezhi, Jia, Fu, Su, Xiaosan, Li, Xiufang, Sun, Ruifen, Li, Junmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242983/
https://www.ncbi.nlm.nih.gov/pubmed/37277810
http://dx.doi.org/10.1186/s13018-023-03778-6
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author Yin, Mengxing
Zhou, Dezhi
Jia, Fu
Su, Xiaosan
Li, Xiufang
Sun, Ruifen
Li, Junmin
author_facet Yin, Mengxing
Zhou, Dezhi
Jia, Fu
Su, Xiaosan
Li, Xiufang
Sun, Ruifen
Li, Junmin
author_sort Yin, Mengxing
collection PubMed
description BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs with fewer side effects. The theory of traditional Chinese medicine suggests that YGJ has therapeutic effect on GIOP, but it has not been explained. Therefore, this study aims to explore the protective effect of YGJ on GIOP mouse models and elucidate the underlying mechanism through LC–MS-based metabolomics analysis. METHODS: The general condition of 8 week age male C57BL/6J mice was recorded after 8 weeks of treatment with dexamethasone (DEX) and YGJ. Bone-related parameters and bone morphology were determined by Micro-CT. HE staining was used to observe the pathological changes of bone tissue. Serum levels of bone metabolism markers were detected by ELISA. Liver metabolomics analysis was conducted to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it. RESULTS: After treatment, YGJ significantly reversed the weight loss caused by DEX; increase the number of bone trabecular in ROI region, significantly improve the bone-related parameters of GIOP mice, and increase the levels of alkaline phosphatase and osteocalcin. In the study of metabolic mechanism, YGJ reversed 24 potential markers in GIOP mice. These included cortisol, 3-hydroxybutyric acid, taurine, esculin and uric acid, which are closely associated with osteoporosis. Topological analysis results showed that YGJ had the most significant effect on taurine and hypotaurine metabolism, with − log10 (P) > 2.0 and Impact > 0.4. CONCLUSIONS: Yi-Guan-Jian decoction can increase bone density and improve bone microstructure by regulating the levels of alkaline phosphatase and osteocalcin and reverse bone loss in GIOP mouse model. The underlying metabolic mechanism may be related to taurine and hypotaurine metabolic pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03778-6.
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spelling pubmed-102429832023-06-07 Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis Yin, Mengxing Zhou, Dezhi Jia, Fu Su, Xiaosan Li, Xiufang Sun, Ruifen Li, Junmin J Orthop Surg Res Research Article BACKGROUND: Glucocorticoid-induced osteoporosis (GIOP) is a disease in which long-term use of glucocorticoid causes bone loss, deterioration of bone microstructure and fracture. Currently, clinical drugs targeting this disease have certain side effects. There is still a need to find effective drugs with fewer side effects. The theory of traditional Chinese medicine suggests that YGJ has therapeutic effect on GIOP, but it has not been explained. Therefore, this study aims to explore the protective effect of YGJ on GIOP mouse models and elucidate the underlying mechanism through LC–MS-based metabolomics analysis. METHODS: The general condition of 8 week age male C57BL/6J mice was recorded after 8 weeks of treatment with dexamethasone (DEX) and YGJ. Bone-related parameters and bone morphology were determined by Micro-CT. HE staining was used to observe the pathological changes of bone tissue. Serum levels of bone metabolism markers were detected by ELISA. Liver metabolomics analysis was conducted to search for the significant markers of anti-GIOP of YGJ and the metabolic pathway affecting it. RESULTS: After treatment, YGJ significantly reversed the weight loss caused by DEX; increase the number of bone trabecular in ROI region, significantly improve the bone-related parameters of GIOP mice, and increase the levels of alkaline phosphatase and osteocalcin. In the study of metabolic mechanism, YGJ reversed 24 potential markers in GIOP mice. These included cortisol, 3-hydroxybutyric acid, taurine, esculin and uric acid, which are closely associated with osteoporosis. Topological analysis results showed that YGJ had the most significant effect on taurine and hypotaurine metabolism, with − log10 (P) > 2.0 and Impact > 0.4. CONCLUSIONS: Yi-Guan-Jian decoction can increase bone density and improve bone microstructure by regulating the levels of alkaline phosphatase and osteocalcin and reverse bone loss in GIOP mouse model. The underlying metabolic mechanism may be related to taurine and hypotaurine metabolic pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13018-023-03778-6. BioMed Central 2023-06-05 /pmc/articles/PMC10242983/ /pubmed/37277810 http://dx.doi.org/10.1186/s13018-023-03778-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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 Article
Yin, Mengxing
Zhou, Dezhi
Jia, Fu
Su, Xiaosan
Li, Xiufang
Sun, Ruifen
Li, Junmin
Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title_full Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title_fullStr Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title_full_unstemmed Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title_short Metabolomics analysis of the potential mechanism of Yi-Guan-Jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
title_sort metabolomics analysis of the potential mechanism of yi-guan-jian decoction to reverse bone loss in glucocorticoid-induced osteoporosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10242983/
https://www.ncbi.nlm.nih.gov/pubmed/37277810
http://dx.doi.org/10.1186/s13018-023-03778-6
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