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Cited by 527

The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.

Tumor Necrosis Factor-α Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway

Tintut, Yin, Patel, Jignesh, Parhami, Farhad, Demer, Linda L.·2000·Circulation

Abstract

Background —Vascular calcification is an ectopic calcification that commonly occurs in atherosclerosis. Because tumor necrosis factor-α (TNF-α), a pleiotropic cytokine found in atherosclerotic lesions, is also a regulator of bone formation, we investigated the role of TNF-α in in vitro vascular calcification. Methods and Results —A cloned subpopulation of bovine aortic smooth muscle cells previously shown capable of osteoblastic differentiation was treated with TNF-α, and osteoblastic differentiation and mineralization were assessed. Treatment of vascular cells with TNF-α for 3 days induced an osteoblast-like morphology. It also enhanced both activity and mRNA expression of alkaline phosphatase, an early marker of osteoblastic differentiation. Continuous treatment with TNF-α for 10 days enhanced matrix mineralization as measured by radiolabeled calcium incorporation in the matrix. Pretreatment of cells with a protein kinase A–specific inhibitor, KT5720, attenuated cell morphology, the alkaline phosphatase activity, and mineralization induced by TNF-α. Consistent with this, the intracellular cAMP level was elevated after TNF-α treatment. Electrophoretic mobility shift assay demonstrated that TNF-α enhanced DNA binding of osteoblast specific factor (Osf2), AP1, and CREB, transcription factors that are important for osteoblastic differentiation. Conclusions —These results suggest that TNF-α enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular cells through the cAMP pathway.

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Metadata

Authors
Tintut, Y., Patel, J., Parhami, F., & Demer, L. L.
Venue
Circulation
Published
2000-11-21
Volume
102
Issue
21
Pages
2636-2642
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W2170893247
Cited by
527
References
39
FWCI
9.49
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Tumor Necrosis Factor-α Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway. https://app.cochat.ai/papers/10.1161/01.cir.102.21.2636
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Tintut, Y., Patel, J., Parhami, F., & Demer, L. L. (2000). Tumor Necrosis Factor-α Promotes In Vitro Calcification of Vascular Cells via the cAMP Pathway. Circulation. https://doi.org/10.1161/01.cir.102.21.2636

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