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Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats

BACKGROUND: Metformin (MF) is a widely used biguanide oral hypoglycemic agent, which has obvious anti-inflammatory and immunomodulatory effects. However, the mechanism of MF on rheumatoid arthritis (RA) remains uncertain. In this study, we investigated the therapeutic effects of MF on collagen-induc...

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Autores principales: Fan, Kai-Jian, Wu, Jing, Wang, Qi-Shan, Xu, Bing-Xin, Zhao, Fu-Tao, Wang, Ting-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791269/
https://www.ncbi.nlm.nih.gov/pubmed/33437764
http://dx.doi.org/10.21037/atm-20-3042
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author Fan, Kai-Jian
Wu, Jing
Wang, Qi-Shan
Xu, Bing-Xin
Zhao, Fu-Tao
Wang, Ting-Yu
author_facet Fan, Kai-Jian
Wu, Jing
Wang, Qi-Shan
Xu, Bing-Xin
Zhao, Fu-Tao
Wang, Ting-Yu
author_sort Fan, Kai-Jian
collection PubMed
description BACKGROUND: Metformin (MF) is a widely used biguanide oral hypoglycemic agent, which has obvious anti-inflammatory and immunomodulatory effects. However, the mechanism of MF on rheumatoid arthritis (RA) remains uncertain. In this study, we investigated the therapeutic effects of MF on collagen-induced arthritis (CIA). METHODS: CIA was induced in rats by intradermal injection of a mixture of bovine type II collagen and incomplete Freund’s adjuvant (IFA) on day 0 and day 7 through the base of the tail. Intraperitoneal injection of MF (100 mg/kg) was given every 3 days, from day 14 for 3 weeks. The effects of MF on arthritis-induced systemic inflammation and synovitis were studied by pathological analysis of the knee joint and serological examination of peripheral blood in CIA rats. The bone protection effect of MF was studied by microscopic computed tomography (micro-CT) and histological analysis of the knee joint. The effects of MF on chondrocytes in CIA rats were studied by detecting the relevant pro-apoptotic mediators in the chondrocytes. RESULTS: After administration of MF in CIA rats, systemic inflammation and synovitis caused by arthritis were significantly suppressed. Histomorphometry and micro-CT analysis of the knee joint revealed that MF can protect bone by inhibiting the changes of trabecular bone in CIA rats. Histological analysis of the knee joint found that MF can inhibit osteoclast formation and degradation of the cartilage layer matrix. Detection of the relevant pro-apoptotic mediators in chondrocytes revealed that MF can significantly inhibit the apoptosis of chondrocytes in CIA rats. CONCLUSIONS: Our study showed that MF can inhibit systemic inflammation and synovitis and plays a role in bone protection by inhibiting cartilage layer matrix degradation, osteoclast formation, and chondrocyte apoptosis.
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spelling pubmed-77912692021-01-11 Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats Fan, Kai-Jian Wu, Jing Wang, Qi-Shan Xu, Bing-Xin Zhao, Fu-Tao Wang, Ting-Yu Ann Transl Med Original Article BACKGROUND: Metformin (MF) is a widely used biguanide oral hypoglycemic agent, which has obvious anti-inflammatory and immunomodulatory effects. However, the mechanism of MF on rheumatoid arthritis (RA) remains uncertain. In this study, we investigated the therapeutic effects of MF on collagen-induced arthritis (CIA). METHODS: CIA was induced in rats by intradermal injection of a mixture of bovine type II collagen and incomplete Freund’s adjuvant (IFA) on day 0 and day 7 through the base of the tail. Intraperitoneal injection of MF (100 mg/kg) was given every 3 days, from day 14 for 3 weeks. The effects of MF on arthritis-induced systemic inflammation and synovitis were studied by pathological analysis of the knee joint and serological examination of peripheral blood in CIA rats. The bone protection effect of MF was studied by microscopic computed tomography (micro-CT) and histological analysis of the knee joint. The effects of MF on chondrocytes in CIA rats were studied by detecting the relevant pro-apoptotic mediators in the chondrocytes. RESULTS: After administration of MF in CIA rats, systemic inflammation and synovitis caused by arthritis were significantly suppressed. Histomorphometry and micro-CT analysis of the knee joint revealed that MF can protect bone by inhibiting the changes of trabecular bone in CIA rats. Histological analysis of the knee joint found that MF can inhibit osteoclast formation and degradation of the cartilage layer matrix. Detection of the relevant pro-apoptotic mediators in chondrocytes revealed that MF can significantly inhibit the apoptosis of chondrocytes in CIA rats. CONCLUSIONS: Our study showed that MF can inhibit systemic inflammation and synovitis and plays a role in bone protection by inhibiting cartilage layer matrix degradation, osteoclast formation, and chondrocyte apoptosis. AME Publishing Company 2020-12 /pmc/articles/PMC7791269/ /pubmed/33437764 http://dx.doi.org/10.21037/atm-20-3042 Text en 2020 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Fan, Kai-Jian
Wu, Jing
Wang, Qi-Shan
Xu, Bing-Xin
Zhao, Fu-Tao
Wang, Ting-Yu
Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title_full Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title_fullStr Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title_full_unstemmed Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title_short Metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
title_sort metformin inhibits inflammation and bone destruction in collagen-induced arthritis in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791269/
https://www.ncbi.nlm.nih.gov/pubmed/33437764
http://dx.doi.org/10.21037/atm-20-3042
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