Related Experiment Videos
Nitric oxide: an important articular free radical
G A Murrell1, M M Doland, D Jang
1Laboratory for Soft Tissue Research, Hospital for Special Surgery, New York, NY 10021, USA.
The Journal of Bone and Joint Surgery. American Volume
|February 1, 1996
Summary
Chondrocytes are the main source of nitric oxide (NO) in joints during inflammation. This NO production can be inhibited by certain drugs, offering potential therapeutic targets for arthritis.
Area of Science:
- Biochemistry
- Immunology
- Rheumatology
Background:
- Nitric oxide (NO) is implicated in inflammatory joint diseases like rheumatoid arthritis and osteoarthrosis.
- Nitric oxide synthases (NOS) are enzymes responsible for NO production.
- Understanding NO sources in joints is crucial for developing targeted therapies.
Purpose of the Study:
- To identify the primary sources of nitric oxide (NO) in joint tissues.
- To investigate the potential inhibition of NO production by dexamethasone and methotrexate.
- To explore the role of chondrocytes and other joint cells in NO synthesis.
Main Methods:
- Analysis of nitrite (stable NO metabolite) release from human and bovine cartilage and chondrocyte cultures.
- Stimulation with inflammatory mediators: endotoxin, interleukin-1 beta, and tumor necrosis factor-alpha.
- Inhibition studies using NOS inhibitors (N omega-nitro-L-arginine methyl ester, aminoguanidine) and anti-inflammatory drugs (methotrexate, dexamethasone).
Main Results:
- Chondrocytes and cartilage explants produced significant nitrite upon stimulation, indicating inducible nitric oxide synthase (iNOS) activity.
- Nitrite production was dose- and time-dependent on inflammatory stimuli and inhibited by NOS inhibitors.
- High concentrations of methotrexate and dexamethasone inhibited iNOS in bovine chondrocytes.
- Menisci, synovial tissue, and ligaments showed minimal or no constitutive or inducible NO production.
Conclusions:
- Chondrocytes are the predominant source of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in inflamed or infected joints.
- Dexamethasone and methotrexate demonstrate inhibitory effects on NO production in chondrocytes.
- These findings highlight chondrocytes as key players in joint inflammation and potential targets for therapeutic intervention.