Nitric oxide and proteoglycan turnover in rabbit articular cartilage

M. Stefanovic-Racic, M. O. Mollers, L. A. Miller, Christopher H Evans

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Articular chondrocytes are known to synthesize large amounts of nitric oxide in response to exposure to interleukin-1, but the role of this radical in proteoglycan turnover remains controversial. In this study, we used two different inhibitors of nitric oxide synthase, N(G)-methyl-L-arginine and thiocitrulline, to study the effects of nitric oxide on the synthesis and breakdown of proteoglycan in rabbit articular cartilage. Synthesis of nitric oxide by cartilage slices in response to treatment with interleukin-1 and a partially purified mixture of synovial cytokines known as chondrocyte- activating factors peaked during the first 2 days of culture and then fell to low levels, despite daily replenishment with fresh medium and cytokines to the cultures. The production of nitric oxide was completely inhibited by N(G)-methyl-L-arginine and thiocitrulline. Interleukin-1 and the chondrocyte- activating factors inhibited proteoglycan synthesis and accelerated proteoglycan breakdown in the slices of cartilage. Both nitric oxide synthase inhibitors substantially counteracted the suppression of proteoglycan synthesis but exacerbated proteoglycan catabolism occurring in response to interleukin-1 and the chondrocyte-activating factors. The accelerated catabolism was associated with increased levels of matrix metalloproteinases in the conditioned medium. This dual effect of nitric oxide complicates decision making with regard to the possible clinical applications of nitric oxide agonists or antagonists in diseases of cartilage.

Original languageEnglish (US)
Pages (from-to)442-449
Number of pages8
JournalJournal of Orthopaedic Research
Volume15
Issue number3
DOIs
StatePublished - May 1997
Externally publishedYes

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Articular Cartilage
Proteoglycans
Nitric Oxide
Chondrocytes
Rabbits
Interleukin-1
Nitric Oxide Synthase
Cartilage
Arginine
Cartilage Diseases
Cytokines
Conditioned Culture Medium
Matrix Metalloproteinases
Decision Making
Joints

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

Nitric oxide and proteoglycan turnover in rabbit articular cartilage. / Stefanovic-Racic, M.; Mollers, M. O.; Miller, L. A.; Evans, Christopher H.

In: Journal of Orthopaedic Research, Vol. 15, No. 3, 05.1997, p. 442-449.

Research output: Contribution to journalArticle

Stefanovic-Racic, M. ; Mollers, M. O. ; Miller, L. A. ; Evans, Christopher H. / Nitric oxide and proteoglycan turnover in rabbit articular cartilage. In: Journal of Orthopaedic Research. 1997 ; Vol. 15, No. 3. pp. 442-449.
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