Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8525, Japan.
Int J Mol Sci. 2021 Aug 25;22(17):9204. doi: 10.3390/ijms22179204.
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 (ATR) and type 2 (ATR), 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 ATR 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 -deficient RCS cells generated by the CRISPR-Cas9 system, and () expression increased. Losartan, an ATR antagonist, blocked the ANG II-induced decrease in CCN2 production and expression in RCS cells. These findings suggest that ATR blockade reduces ANG II-induced chondrocyte degeneration. Interestingly, ATR-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-ATR axis.
肾素-血管紧张素系统（RAS）不仅控制着血压等全身功能，还控制着局部组织特异性事件。先前的研究表明，血管紧张素 II 受体 1（ATR1）和 2（ATR2），RAS 的两个组成部分，在软骨细胞中表达。然而，通过这些受体发挥的血管紧张素 II（ANG II）对软骨细胞代谢的影响尚不完全清楚。在这项研究中，我们研究了 ANG II 和 ATR 阻断对软骨细胞增殖和分化的影响。首先，我们观察到 ANG II 显著抑制大鼠软骨细胞 RCS 细胞的增殖和糖胺聚糖含量。此外，ANG II 通过增加 MMP9 降低了 CCN2，这是软骨细胞的合成代谢因子。在通过 CRISPR-Cas9 系统生成的缺乏 的 RCS 细胞中， 和 的表达增加。ATR 拮抗剂氯沙坦阻断了 ANG II 诱导的 RCS 细胞中 CCN2 产生和 的表达减少。这些发现表明 ATR 阻断可减少 ANG II 诱导的软骨细胞退化。有趣的是，ATR 阳性细胞定位于 7 月龄小鼠关节软骨表面，随着年龄的增长在整个关节软骨中扩展。这些发现表明，ANG II 通过 ANG II-ATR 轴调节与年龄相关的软骨退化。
