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Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis

Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential inv...

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Autores principales: Akagi, Takahiko, Mukai, Tomoyuki, Mito, Takafumi, Kawahara, Kyoko, Tsuji, Shoko, Fujita, Shunichi, Uchida, Haruhito A., Morita, Yoshitaka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312645/
https://www.ncbi.nlm.nih.gov/pubmed/32532031
http://dx.doi.org/10.3390/ijms21114145
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author Akagi, Takahiko
Mukai, Tomoyuki
Mito, Takafumi
Kawahara, Kyoko
Tsuji, Shoko
Fujita, Shunichi
Uchida, Haruhito A.
Morita, Yoshitaka
author_facet Akagi, Takahiko
Mukai, Tomoyuki
Mito, Takafumi
Kawahara, Kyoko
Tsuji, Shoko
Fujita, Shunichi
Uchida, Haruhito A.
Morita, Yoshitaka
author_sort Akagi, Takahiko
collection PubMed
description Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.
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spelling pubmed-73126452020-06-26 Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis Akagi, Takahiko Mukai, Tomoyuki Mito, Takafumi Kawahara, Kyoko Tsuji, Shoko Fujita, Shunichi Uchida, Haruhito A. Morita, Yoshitaka Int J Mol Sci Article Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis. MDPI 2020-06-10 /pmc/articles/PMC7312645/ /pubmed/32532031 http://dx.doi.org/10.3390/ijms21114145 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Akagi, Takahiko
Mukai, Tomoyuki
Mito, Takafumi
Kawahara, Kyoko
Tsuji, Shoko
Fujita, Shunichi
Uchida, Haruhito A.
Morita, Yoshitaka
Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title_full Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title_fullStr Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title_full_unstemmed Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title_short Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
title_sort effect of angiotensin ii on bone erosion and systemic bone loss in mice with tumor necrosis factor-mediated arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312645/
https://www.ncbi.nlm.nih.gov/pubmed/32532031
http://dx.doi.org/10.3390/ijms21114145
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