TY - JOUR
T1 - Effect of angiotensin II on bone erosion and systemic bone loss in mice with tumor necrosis factor-mediated arthritis
AU - Akagi, Takahiko
AU - Mukai, Tomoyuki
AU - Mito, Takafumi
AU - Kawahara, Kyoko
AU - Tsuji, Shoko
AU - Fujita, Shunichi
AU - Uchida, Haruhito A.
AU - Morita, Yoshitaka
N1 - Funding Information:
Funding: This work was supported by grants from JSPS KAKENHI (20K08814 and 17K09991 to Y.M.), Kawasaki Medical School (Research Project Grants; R01-060 and 30-051 to Y.M.), and UCB Japan (T.M., Tomoyuki Mukai).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - 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.
AB - 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.
KW - Angiotensin II
KW - Angiotensin II type 1 receptor
KW - Arthritis
KW - Bone erosion
KW - Inflammation
KW - Renin-angiotensin system
KW - Tumor necrosis factor
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U2 - 10.3390/ijms21114145
DO - 10.3390/ijms21114145
M3 - Article
C2 - 32532031
AN - SCOPUS:85086408712
SN - 1661-6596
VL - 21
SP - 1
EP - 19
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 11
M1 - 4145
ER -