ID | 62437 |
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Author |
Nishida, Takashi
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Akashi, Sho
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Takigawa, Masaharu
Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Kubota, Satoshi
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
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Abstract | The renin-angiotensin system (RAS) controls not only systemic functions, such as blood pressure, but also local tissue-specific events. Previous studies have shown that angiotensin II receptor type 1 (AT(1)R) and type 2 (AT(2)R), two RAS components, are expressed in chondrocytes. However, the angiotensin II (ANG II) effects exerted through these receptors on chondrocyte metabolism are not fully understood. In this study, we investigated the effects of ANG II and AT(1)R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly suppressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Additionally, ANG II decreased CCN2, which is an anabolic factor for chondrocytes, via increased MMP9. In Agtr1a-deficient RCS cells generated by the CRISPR-Cas9 system, Ccn2 and Aggrecan (Acan) expression increased. Losartan, an AT(1)R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT(1)R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT(1)R-positive cells, which were localized on the surface of the articular cartilage of 7-month-old mice expanded throughout the articular cartilage with aging. These findings suggest that ANG II regulates age-related cartilage degeneration through the ANG II-AT(1)R axis.
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Keywords | angiotensin II
cellular communication network factor 2 (CCN2)
renin-angiotensin system (RAS)
losartan
angiotensin II type I receptor (AT(1)R)
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Published Date | 2021-08-25
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Publication Title |
International Journal of Molecular Sciences
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Volume | volume22
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Issue | issue17
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Publisher | MDPI
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Start Page | 9204
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ISSN | 1422-0067
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | © 2021 by the authors.
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File Version | publisher
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Related Url | isVersionOf https://doi.org/10.3390/ijms22179204
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License | https://creativecommons.org/licenses/by/4.0/
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Citation | Nishida, T.; Akashi, S.; Takigawa, M.; Kubota, S. Effect of Angiotensin II on Chondrocyte Degeneration and Protection via Differential Usage of Angiotensin II Receptors. Int. J. Mol. Sci. 2021, 22, 9204. https://doi.org/10.3390/ ijms22179204
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Funder Name |
Japan Society for the Promotion of Science
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助成番号 | 17K11641
20K09889
21H03105
19H03817
JP20K20611
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Open Access (Publisher) |
OA
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