2. Academic Validation
  3. Angiotensin II inhibits osteogenic differentiation of isolated synoviocytes by increasing DKK-1 expression

Angiotensin II inhibits osteogenic differentiation of isolated synoviocytes by increasing DKK-1 expression

  • Int J Biochem Cell Biol. 2020 Apr;121:105703. doi: 10.1016/j.biocel.2020.105703.
Yongtao Zhang 1,  Huimin Ding 2,  Qichun Song 3,  Ze Wang 4,  Wanqing Yuan 1,  Yuanzhong Ren 1,  Zhiping Zhao 1,  Changyao Wang 5
Affiliations

Affiliations

  • 1 Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
  • 2 Department of Orthopedics, BenQ Medical Center, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, China.
  • 3 Department of Orthopedics, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China.
  • 4 Department of Emergency Medicine, Qingdao Haici Medical Treatment Group, Qingdao, 266000, Shandong, China.
  • 5 Department of Orthopedics, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China. Electronic address: drchangyaowang@163.com.
PMID: 32014499 DOI: 10.1016/j.biocel.2020.105703
Abstract

The renin-angiotensin system contributes to the pathogenesis of rheumatoid arthritis, but that the mechanism is unclear. This study aims to investigate the effect of angiotensin II (Ang II) on osteogenic differentiation of synoviocytes and the underlying mechanism. Ang II was showed to inhibite osteogenic differentiation of synoviocytes, which was mitigated by a Dickkopf-1 (DKK-1) inhibitor. DKK-1 was upregulated by Ang II, which was weakened by the Ang II type 1 receptor (AT1R) blocker, Reactive Oxygen Species (ROS) scavenger, and p38 inhibitor. Ang II increased the levels of AT1R, ROS, and NADPH Oxidase (NOX), and the upregulations were mitigated by the AT1R blocker or NOX inhibitor. Furthermore, Ang II activated the p38 pathway, which was blocked by the AT1R blocker, ROS scavenger, or siRNA-MKK3. In brief, these results indicate that Ang II upregulates NOX expression and ROS production via AT1R, activates the MKK3/p38 signaling, and in turn upregulates DKK-1 expression, participating in the inhibition of osteogenic differentiation of synoviocytes.

Keywords

Angiotensin II; Dickkopf-1; Osteogenic differentiation; Synoviocytes; p38 pathway.

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