Effect of angiotensin ii on chondrocyte degeneration and protection via differential usage of angiotensin ii receptors

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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 (AT1R) and type 2 (AT2R), two RAS components, are expressed in chondrocytes. How-ever, 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 AT1R blockade on chondrocyte proliferation and differentiation. Firstly, we observed that ANG II significantly sup-pressed cell proliferation and glycosaminoglycan content in rat chondrocytic RCS cells. Addition-ally, 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 AT1R antagonist, blocked the ANG II-induced decrease in CCN2 production and Acan expression in RCS cells. These findings suggest that AT1R blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, AT1R-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–AT1R axis.

Original languageEnglish
Article number9204
JournalInternational journal of molecular sciences
Volume22
Issue number17
DOIs
Publication statusPublished - Sep 1 2021
Externally publishedYes

Keywords

  • Angiotensin II
  • Angiotensin II type I receptor (AT1R)
  • Cellular communication network factor 2 (CCN2)
  • Losartan
  • Renin–angiotensin system (RAS)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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