Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis

被引:20
作者
Akagi, Takahiko [1 ]
Mukai, Tomoyuki [1 ]
Mito, Takafumi [1 ]
Kawahara, Kyoko [1 ]
Tsuji, Shoko [1 ]
Fujita, Shunichi [1 ]
Uchida, Haruhito A. [2 ]
Morita, Yoshitaka [1 ]
机构
[1] Kawasaki Med Sch, Dept Rheumatol, Kurashiki, Okayama 7010192, Japan
[2] Okayama Univ, Dept Chron Kidney Dis & Cardiovasc Dis, Grad Sch Med Dent & Pharmaceut Sci, Tsushima, Okayama 7000914, Japan
关键词
angiotensin II; arthritis; bone erosion; inflammation; tumor necrosis factor; renin-angiotensin system; angiotensin II type 1 receptor; ABDOMINAL AORTIC-ANEURYSMS; RHEUMATOID-ARTHRITIS; THERAPEUTIC TARGET; RECEPTOR; OSTEOPOROSIS; INVOLVEMENT; ACTIVATION; DIAGNOSIS;
D O I
10.3390/ijms21114145
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:1 / 19
页数:19
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