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Nitric oxide in osteoarthritis
R Studer1, D Jaffurs, M Stefanovic-Racic
1Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Osteoarthritis and Cartilage
|July 27, 1999
Summary
Activated chondrocytes produce nitric oxide (NO), a key factor in osteoarthritis (OA) pathogenesis. Endogenously produced NO inhibits cartilage matrix synthesis by interfering with growth factors.
Area of Science:
- Biochemistry
- Cell Biology
- Rheumatology
Background:
- Activated articular chondrocytes produce significant nitric oxide (NO).
- Nitric oxide (NO) is implicated in the pathogenesis of osteoarthritis (OA).
- Endogenously produced NO likely exerts local effects within cartilage due to its short half-life.
Purpose of the Study:
- To investigate the role of endogenously produced nitric oxide (NO) in regulating chondrocyte matrix synthesis.
- To determine if NO inhibits matrix synthesis independently of apoptosis.
- To explore the mechanism by which NO affects matrix production, particularly in response to growth factors.
Main Methods:
- Transduction of chondrocytes with the inducible nitric oxide synthase (iNOS or NOS-2) gene to achieve endogenous NO production.
- Assessment of matrix synthesis in response to IL-1 and IGF-1.
- Evaluation of cell viability to detect apoptosis or cell death.
- Measurement of TGF-beta(1) production.
Main Results:
- Endogenously produced NO by iNOS-expressing chondrocytes inhibited matrix synthesis.
- High levels of NO did not induce apoptosis or cell death.
- Nitric oxide (NO) inhibited TGF-beta(1) production in IL-1-treated cells.
- NO decreased matrix production in response to IGF-1.
Conclusions:
- Endogenously produced nitric oxide (NO) inhibits chondrocyte matrix synthesis.
- The inhibitory effect of NO on matrix production is not mediated by apoptosis.
- Nitric oxide (NO) may inhibit matrix synthesis by interfering with autocrine and paracrine signaling pathways, such as those involving TGF-beta(1) and IGF-1.