Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: A potential regulatory mechanism of valvular calcification

  • Authors:
    • Jens J. Kaden
    • Refika Kiliç
    • Aslihan Sarikoç
    • Siegfried Hagl
    • Siegfried Lang
    • Ursula Hoffmann
    • Martina Brueckmann
    • Martin Borggrefe
  • View Affiliations

  • Published online on: November 1, 2005     https://doi.org/10.3892/ijmm.16.5.869
  • Pages: 869-872
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Abstract

Valvular calcification during calcific aortic stenosis is associated with morphological features of bone formation and expression of various bone-associated proteins, which are both associated with marked leukocyte infiltration of the calcified valve areas. The pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) is abundantly present in areas of leukocyte infiltration in stenotic aortic valves. We therefore hypothesized that valvular calcification might be actively regulated by an inflammatory process involving TNF-α. Upon stimulation with TNF-α, human aortic valve myofibroblasts cultured under mineralizing conditions showed an increased formation of calcified, alkaline phosphatase (ALP)-enriched cell nodules, ALP activity, concentration of the bone-type ALP isoenzyme, and concentration of osteocalcin, all of which are markers of an osteoblast-like cellular phenotype. By electrophoretic mobility shift assay, DNA binding of the essential osteoblastic transcription factor Cbfa-1 was increased compared to untreated controls. These results support the concept that aortic valve calcification is associated with an osteoblast-like phenotype of local myofibroblasts. In addition, the data demonstrate direct mechanistic evidence that aortic valve calcification may be actively regulated by an inflammatory process involving TNF-α.

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November 2005
Volume 16 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Kaden JJ, Kiliç R, Sarikoç A, Hagl S, Lang S, Hoffmann U, Brueckmann M and Borggrefe M: Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: A potential regulatory mechanism of valvular calcification. Int J Mol Med 16: 869-872, 2005.
APA
Kaden, J.J., Kiliç, R., Sarikoç, A., Hagl, S., Lang, S., Hoffmann, U. ... Borggrefe, M. (2005). Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: A potential regulatory mechanism of valvular calcification. International Journal of Molecular Medicine, 16, 869-872. https://doi.org/10.3892/ijmm.16.5.869
MLA
Kaden, J. J., Kiliç, R., Sarikoç, A., Hagl, S., Lang, S., Hoffmann, U., Brueckmann, M., Borggrefe, M."Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: A potential regulatory mechanism of valvular calcification". International Journal of Molecular Medicine 16.5 (2005): 869-872.
Chicago
Kaden, J. J., Kiliç, R., Sarikoç, A., Hagl, S., Lang, S., Hoffmann, U., Brueckmann, M., Borggrefe, M."Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: A potential regulatory mechanism of valvular calcification". International Journal of Molecular Medicine 16, no. 5 (2005): 869-872. https://doi.org/10.3892/ijmm.16.5.869