Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
Effect of Angiotensin II on Bone Erosion and Systemic Bone Loss in Mice with Tumor Necrosis Factor-Mediated Arthritis
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DOI：
10.3390/ijms21114145
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发表时间：
2020-06-01
影响因子：
5.6
通讯作者：
Morita, Yoshitaka
中科院分区：
文献类型：
--
作者：
Akagi, Takahiko;Mukai, Tomoyuki;Morita, Yoshitaka
血管紧张素II （Angiotensin II, Ang II）是肾素-血管紧张素系统（renin-angiotensin system， RAS）的主要效应肽，调控心血管系统。据报道RAS也参与骨代谢。RAS成分的上调已在关节炎滑膜组织中显示，提示Ang II可能参与关节炎。因此，在本研究中，我们研究了Ang II在关节炎患者骨侵蚀和系统性骨质流失中的作用。通过渗透泵注入肿瘤坏死因子转基因（TNFtg）小鼠。Ang II输注对临床和组织学炎症的严重程度没有显著影响，但炎症关节的骨侵蚀明显增加。II型给药不影响胫骨或椎骨的骨量。为了抑制内源性Ang II，将Ang II型1受体（AT1R）缺陷小鼠与TNFtg小鼠杂交。AT1R基因缺失对炎症、骨质侵蚀或全身性骨质流失没有显著影响。这些结果表明，RAS的过度全身激活可能是进行性关节破坏的一个危险因素。我们的研究结果对炎性骨破坏的发病机制和类风湿性关节炎患者RAS抑制剂的临床应用具有重要意义。
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.