Abstract
Angiotensin II (Ang II) is the main effector peptide of the renin-angiotensin system (RAS), which regulates the cardiovascular system. The RAS is reportedly also involved in bone metabolism. The upregulation of RAS components has been shown in arthritic synovial tissues, suggesting the potential involvement of Ang II in arthritis. Accordingly, in the present study, we investigated the role of Ang II in bone erosion and systemic bone loss in arthritis. Ang II was infused by osmotic pumps in tumor necrosis factor-transgenic (TNFtg) mice. Ang II infusion did not significantly affect the severity of clinical and histological inflammation, whereas bone erosion in the inflamed joints was significantly augmented. Ang II administration did not affect the bone mass of the tibia or vertebra. To suppress endogenous Ang II, Ang II type 1 receptor (AT1R)-deficient mice were crossed with TNFtg mice. Genetic deletion of AT1R did not significantly affect inflammation, bone erosion, or systemic bone loss. These results suggest that excessive systemic activation of the RAS can be a risk factor for progressive joint destruction. Our findings indicate an important implication for the pathogenesis of inflammatory bone destruction and for the clinical use of RAS inhibitors in patients with rheumatoid arthritis.
Highlights
Rheumatoid arthritis is a chronic inflammatory disorder that can cause painful swelling and bone erosion in the inflamed joints [1]
As a first step to explore the effect of Angiotensin II (Ang II) on arthritis, the expression of Agtr1a, encoding Ang II type 1 receptor (AT1R), in the joints was assessed by quantitative polymerase chain reaction
We sought to clarify the impact of excessive Ang II and inhibition of the endogenous renin-angiotensin system (RAS) on bone erosion and systemic bone loss in a tumor necrosis factor (TNF)-mediated arthritic condition
Summary
Rheumatoid arthritis is a chronic inflammatory disorder that can cause painful swelling and bone erosion in the inflamed joints [1]. The accumulation of joint damage results in long-lasting pain and deformity of the affected joints [2]. Persistent systemic inflammation in rheumatoid arthritis can cause tissue damage in organs such as the lungs, heart, eyes, and bone [3]. Increased inflammatory cytokines affect bone metabolism throughout the body and decrease bone mass and strength, leading to increased risks of osteoporosis and fracture [4]. Joint deformities impair activities of daily life and exacerbate osteoporosis in patients with rheumatoid arthritis. This highlights the importance of resolving joint damage and systemic bone loss issues in these patients
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