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Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage.

Publication ,  Journal Article
Cernanec, J; Guilak, F; Weinberg, JB; Pisetsky, DS; Fermor, B
Published in: Arthritis Rheum
April 2002

OBJECTIVE: Articular cartilage is an avascular tissue that functions at a lower oxygen tension than do most tissues. With mobilization, arthritic joints may undergo cycles of hypoxia and reoxygenation. The goal of this study was to determine the effects of hypoxia and reoxygenation on cytokine-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production in articular cartilage. METHODS: Porcine cartilage explants were incubated at 37 degrees C for 72 hours in either 1% O(2) (hypoxia) or 20% O(2) (normoxia) in media supplemented with interleukin-1alpha (IL-1alpha) or tumor necrosis factor alpha (TNFalpha), with or without the NO synthase 2 (NOS2) selective inhibitor 1400W. Culture media were then removed and replaced with freshly prepared media and incubated for a further 24 hours in normoxia. RESULTS: NO levels were significantly higher in explants supplemented with IL-1alpha and TNFalpha compared with controls, in both hypoxia and normoxia. Compared with normoxia, hypoxia decreased IL-1alpha- and TNFalpha-induced NO production significantly. Reoxygenation of hypoxic explants resulted in sustained significant NO production in response to either cytokine. However, comparably high levels of NO production were not sustained in explants cultured continuously in normoxia. Although IL-1alpha alone did not significantly increase PGE(2) production, significant PGE(2) superinduction occurred in cartilage stimulated with IL-1alpha and the NOS2 inhibitor 1400W compared with stimulation with IL-1alpha alone in hypoxia, but not in normoxia. CONCLUSION: Oxygen tension significantly affects cytokine-induced proinflammatory mediator production in articular cartilage. Furthermore, hypoxia alters NO mediation of PGE(2) production. Hypoxia and reoxygenation can affect cytokine-induced proinflammatory mediator production, suggesting that oxygen tension may influence inflammation associated with cartilage injury and disease.

Duke Scholars

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

April 2002

Volume

46

Issue

4

Start / End Page

968 / 975

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Swine
  • Oxygen
  • Osteoarthritis
  • Nitric Oxide
  • Interleukin-1
  • Hypoxia
  • Female
  • Dinoprostone
  • Cells, Cultured
 

Citation

APA
Chicago
ICMJE
MLA
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Cernanec, J., Guilak, F., Weinberg, J. B., Pisetsky, D. S., & Fermor, B. (2002). Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage. Arthritis Rheum, 46(4), 968–975. https://doi.org/10.1002/art.10213
Cernanec, Julie, Farshid Guilak, J Brice Weinberg, David S. Pisetsky, and Beverley Fermor. “Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage.Arthritis Rheum 46, no. 4 (April 2002): 968–75. https://doi.org/10.1002/art.10213.
Cernanec J, Guilak F, Weinberg JB, Pisetsky DS, Fermor B. Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage. Arthritis Rheum. 2002 Apr;46(4):968–75.
Cernanec, Julie, et al. “Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage.Arthritis Rheum, vol. 46, no. 4, Apr. 2002, pp. 968–75. Pubmed, doi:10.1002/art.10213.
Cernanec J, Guilak F, Weinberg JB, Pisetsky DS, Fermor B. Influence of hypoxia and reoxygenation on cytokine-induced production of proinflammatory mediators in articular cartilage. Arthritis Rheum. 2002 Apr;46(4):968–975.
Journal cover image

Published In

Arthritis Rheum

DOI

ISSN

0004-3591

Publication Date

April 2002

Volume

46

Issue

4

Start / End Page

968 / 975

Location

United States

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Swine
  • Oxygen
  • Osteoarthritis
  • Nitric Oxide
  • Interleukin-1
  • Hypoxia
  • Female
  • Dinoprostone
  • Cells, Cultured