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

Area of Science:

• Rheumatology
• Molecular Biology
• Cell Biology

Background:

• The renin-angiotensin system's role in rheumatoid arthritis (RA) pathogenesis is implicated but mechanistically unclear.
• Osteogenic differentiation of synoviocytes is crucial for joint integrity in RA.

Purpose of the Study:

• To investigate the impact of angiotensin II (Ang II) on synoviocyte osteogenic differentiation.
• To elucidate the molecular mechanisms underlying Ang II's effects in RA.

Main Methods:

• In vitro study using synoviocytes.
• Treatment with Ang II, AT1R blockers, ROS scavengers, NOX inhibitors, p38 inhibitors, and DKK-1 inhibitors.
• Analysis of AT1R, ROS, NADPH oxidase (NOX), p38 pathway activation, and DKK-1 expression.

Main Results:

• Ang II inhibited osteogenic differentiation of synoviocytes, an effect reversed by a DKK-1 inhibitor.
• Ang II upregulated DKK-1 expression via AT1R, reactive oxygen species (ROS), and p38 signaling.
• Ang II increased AT1R, ROS, and NOX levels, activating the MKK3/p38 pathway.

Conclusions:

• Ang II inhibits osteogenic differentiation in RA by upregulating NOX and ROS production through AT1R.
• Activation of the MKK3/p38 signaling pathway by Ang II leads to increased DKK-1 expression.
• The Ang II/AT1R/ROS/p38/DKK-1 axis is a key player in RA pathogenesis, affecting synoviocyte osteogenic differentiation.