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

2020 ◽  
Vol 21 (11) ◽  
pp. 4145 ◽  
Author(s):  
Takahiko Akagi ◽  
Tomoyuki Mukai ◽  
Takafumi Mito ◽  
Kyoko Kawahara ◽  
Shoko Tsuji ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Tumor Necrosis ◽  
Bone Erosion ◽  
Joint Destruction ◽  
Bone Destruction ◽  
Ang Ii ◽  
Necrosis Factor ◽  
Systemic Bone Loss

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.

scholarly journals Zoledronic acid protects against local and systemic bone loss in tumor necrosis factor-mediated arthritis

2004 ◽  
Vol 50 (7) ◽  
pp. 2327-2337 ◽  
Author(s):  
Petra Herrak ◽  
Birgit Görtz ◽  
Silvia Hayer ◽  
Kurt Redlich ◽  
Erika Reiter ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Tumor Necrosis ◽  
Necrosis Factor ◽  
Systemic Bone Loss

scholarly journals Tumor necrosis factor-α potentiates the effects of angiotensin II on subfornical organ neurons

2018 ◽  
Vol 315 (3) ◽  
pp. R425-R433 ◽  
Author(s):  
Nick J. Simpson ◽  
Alastair V. Ferguson
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Subfornical Organ ◽  
Ang Ii ◽  
Tnf Α ◽  
Intracellular Ca ◽  
Factor Α ◽  
Necrosis Factor

Inflammation is thought to play a fundamental role in the pathophysiology of hypertension and heart failure, although the mechanisms for this remain unclear. Proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), influence the subfornical organ (SFO) to modulate sympathetic activity and blood pressure. The pressor effects of TNF-α in the SFO are partially mediated by angiotensin II (ANG II) receptor type 1 (AT1R), and TNF-α is known to potentiate ANG II-induced hypertension. However, the cellular mechanism of the interaction between TNF-α and ANG II/AT1R signaling remains unknown. In the present study, we performed Ca2+ imaging on dissociated SFO neurons in vitro from male Sprague-Dawley rats to determine whether TNF-α modulates ANG II-induced increases in intracellular Ca2+ in SFO neurons. We first established that a proportion of SFO neurons respond to ANG II, an effect that required AT1R signaling and extracellular Ca2+. We then tested the hypothesis that TNF-α may modulate the effects of ANG II on SFO neurons by examining the effects of TNF-α treatment on the ANG II-induced rise in intracellular Ca2+. We discovered that TNF-α potentiated the ANG II-induced rise in intracellular Ca2+, an effect that was dependent on the duration of TNF-α treatment. Finally, we determined that this potentiation of ANG II-induced Ca2+ activity relied on tetrodotoxin-sensitive voltage-gated Na+ (vgNa+) channels. These data suggest that the potentiation of ANG II/AT1R activity by TNF-α in SFO neurons results from the previously demonstrated ability of this cytokine to modulate the activation threshold of vgNa+ currents.

Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotensin II in rat aorta

1996 ◽  
Vol 80 (6) ◽  
pp. 1891-1897 ◽  
Author(s):  
E. Vicaut ◽  
C. Rasetti ◽  
N. Baudry
Keyword(s):  
Angiotensin Ii ◽  
Tumor Necrosis Factor ◽  
Receptor Agonist ◽  
Tumor Necrosis ◽  
Interleukin 1 ◽  
Thromboxane A2 ◽  
Short Exposure ◽  
Ang Ii ◽  
Thromboxane A2 Receptor ◽  
Necrosis Factor

To better understand the different steps in the changes occurring in vascular reactivity during sepsis, we studied the effects of a short exposure to tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the contraction in response to angiotensin II (ANG II). The contraction elicited by ANG II was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 25 ng/ml TNF or to 5 or 20 ng/ml IL-1. This contraction was not significantly changed by TNF but was 109 +/- 23 and 190 +/- 38% greater than in control rings after 5 and 20 ng/ml IL-1, respectively. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that IL-1 interferes with this modulation. We found that the IL-1-induced increase in contraction in response to ANG II was completely inhibited by 10(-5) M of the cyclooxygenase inhibitor indomethacin and also by 10(-5) M of the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548. Note, however, that in rings exposed to IL-1 the contraction in response to the thromboxane A2-receptor agonist U-46619 was not significantly different from the contraction in unexposed rings. Furthermore, no loss was observed in either the vasodilator response to 10(-9)-10(-4) M of the endothelium-dependent-receptor agonist acetylcholine or in the receptor-independent contraction induced by 60 mM K+. We conclude that short exposure to IL-1, but not to TNF, produces a specific increase in the vasoconstrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This increase might result from an IL-1-induced shift in favor of constrictor prostanoids in the balance of the dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.

scholarly journals Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis

2002 ◽  
Vol 196 (1) ◽  
pp. 77-85 ◽  
Author(s):  
Hong Ji ◽  
Allison Pettit ◽  
Koichiro Ohmura ◽  
Adriana Ortiz-Lopez ◽  
Veronique Duchatelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Inflammatory Cytokines ◽  
Inflammatory Arthritis ◽  
Tumor Necrosis ◽  
Environmental Changes ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Tnf Α ◽  
Necrosis Factor

In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)–α was also required, although seemingly less critically than IL-1, because a proportion of TNF-α–deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFα for bone destruction. The variability in the requirement for TNF-α, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

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