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Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway.

Publication ,  Journal Article
Fermor, B; Weinberg, JB; Pisetsky, DS; Misukonis, MA; Fink, C; Guilak, F
Published in: Osteoarthritis Cartilage
October 2002

OBJECTIVE: Biomechanical signals play important roles in regulating the homeostasis of articular cartilage, but under abnormal conditions may be a critical factor in the onset and progression of arthritis. Prostaglandin E(2) (PGE(2)) and nitric oxide (NO), derived from the enzymes cyclo-oxygenase 2 (COX2) and NO synthase 2 (NOS2), are inflammatory mediators that modulate numerous physiological and pathophysiological processes and are potentially important pharmacological targets in osteoarthritis. The goal of this study was to determine the effect of mechanical compression on PGE(2) production in the presence of selective NOS2 and COX2 inhibitors. METHODS: Articular cartilage explants harvested from 2-3-year-old pigs were subjected to intermittent compression at 0.5Hz over a range of stress magnitudes. PGE(2) and NO production into the media were determined in the presence and absence of the NOS2 inhibitor 1400W or the COX2 inhibitor NS398. COX2 protein levels were determined by immunoblot analysis. RESULTS: Mechanical compression significantly increased NO and PGE(2) synthesis in a manner that was dependent on the magnitude of stress. The selective COX2 inhibitor blocked compression-induced NO and PGE(2) production. Compression in the presence of 1400W further increased COX2 expression resulting in a 10-fold increase in PGE(2) production compared to uncompressed explants with 1400W and a 40-fold increase in PGE(2) compared to uncompressed explants without 1400W. CONCLUSION: Mechanical compression of articular cartilage increased COX2 and PGE(2) production through a NO-dependent pathway, and therefore pharmacological agents that target the NOS2 pathway in cartilage may have a significant influence on prostanoid production in the joint.

Duke Scholars

Published In

Osteoarthritis Cartilage

DOI

ISSN

1063-4584

Publication Date

October 2002

Volume

10

Issue

10

Start / End Page

792 / 798

Location

England

Related Subject Headings

  • Swine
  • Stress, Mechanical
  • Prostaglandin-Endoperoxide Synthases
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Isoenzymes
  • Immunoblotting
  • Female
  • Dinoprostone
 

Citation

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Chicago
ICMJE
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Fermor, B., Weinberg, J. B., Pisetsky, D. S., Misukonis, M. A., Fink, C., & Guilak, F. (2002). Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis Cartilage, 10(10), 792–798. https://doi.org/10.1053/joca.2002.0832
Fermor, B., J. B. Weinberg, D. S. Pisetsky, M. A. Misukonis, C. Fink, and F. Guilak. “Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway.Osteoarthritis Cartilage 10, no. 10 (October 2002): 792–98. https://doi.org/10.1053/joca.2002.0832.
Fermor B, Weinberg JB, Pisetsky DS, Misukonis MA, Fink C, Guilak F. Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis Cartilage. 2002 Oct;10(10):792–8.
Fermor, B., et al. “Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway.Osteoarthritis Cartilage, vol. 10, no. 10, Oct. 2002, pp. 792–98. Pubmed, doi:10.1053/joca.2002.0832.
Fermor B, Weinberg JB, Pisetsky DS, Misukonis MA, Fink C, Guilak F. Induction of cyclooxygenase-2 by mechanical stress through a nitric oxide-regulated pathway. Osteoarthritis Cartilage. 2002 Oct;10(10):792–798.
Journal cover image

Published In

Osteoarthritis Cartilage

DOI

ISSN

1063-4584

Publication Date

October 2002

Volume

10

Issue

10

Start / End Page

792 / 798

Location

England

Related Subject Headings

  • Swine
  • Stress, Mechanical
  • Prostaglandin-Endoperoxide Synthases
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase
  • Nitric Oxide
  • Isoenzymes
  • Immunoblotting
  • Female
  • Dinoprostone