scholarly journals Osteoprotegerin protects against generalized bone loss in tumor necrosis factor-transgenic mice

2003 ◽  
Vol 48 (7) ◽  
pp. 2042-2051 ◽  
Author(s):  
Georg Schett ◽  
Kurt Redlich ◽  
Silvia Hayer ◽  
Jochen Zwerina ◽  
Brad Bolon ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Necrosis Factor

scholarly journals Transgenic Mice Expressing Soluble Tumor Necrosis Factor-Receptor Are Protected Against Bone Loss Caused by Estrogen Deficiency

1997 ◽  
Vol 52 (10) ◽  
pp. 629-630
Author(s):  
Patrick Ammann ◽  
Rene Rizzoli ◽  
Jean-Philippe Bonjour ◽  
Sandrine Bourrin ◽  
Jean-Marc Meyer ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Bone Loss ◽  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Estrogen Deficiency ◽  
Necrosis Factor

Pulmonary-specific expression of tumor necrosis factor-α alters surfactant lipid metabolism

2002 ◽  
Vol 282 (4) ◽  
pp. L735-L742 ◽  
Author(s):  
James L. Carroll ◽  
Diann M. McCoy ◽  
Stephen E. McGowan ◽  
Ronald G. Salome ◽  
Alan J. Ryan ◽  
...  
Keyword(s):  
Tumor Necrosis Factor ◽  
Transgenic Mice ◽  
Tumor Necrosis ◽  
Inflammatory Cells ◽  
Specific Expression ◽  
Tnf Α ◽  
Surfactant Secretion ◽  
Surfactant Lipid ◽  
Factor Α ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-α is a major cytokine implicated in inducing acute and chronic lung injury, conditions associated with surfactant phosphatidylcholine (PtdCho) deficiency. Acutely, TNF-α decreases PtdCho synthesis but stimulates surfactant secretion. To investigate chronic effects of TNF-α, we investigated PtdCho metabolism in a murine transgenic model exhibiting lung-specific TNF-α overexpression. Compared with controls, TNF-α transgenic mice exhibited a discordant pattern of PtdCho metabolism, with a decrease in PtdCho and disaturated PtdCho (DSPtdCho) content in the lung, but increased levels in alveolar lavage. Transgenics had lower activities and increased immunoreactive levels of cytidylyltransferase (CCT), a key PtdCho biosynthetic enzyme. Ceramide, a CCT inhibitor, was elevated, and linoleic acid, a CCT activator, was decreased in transgenics. Radiolabeling studies revealed that alveolar reuptake of DSPtdCho was significantly decreased in transgenic mice. These observations suggest that chronic expression of TNF-α results in a complex pattern of PtdCho metabolism where elevated lavage PtdCho may originate from alveolar inflammatory cells, decreased surfactant reuptake, or altered surfactant secretion. Reduced parenchymal PtdCho synthesis appears to be attributed to CCT enzyme that is physiologically inactivated by ceramide or by diminished availability of activating lipids.

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.

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