Nitric oxide and inflammatory mediators in the perpetuation of osteoarthritis
Abstract
Articular chondrocyte production of nitric oxide (NO) and other inflammatory mediators, such as eicosanoids and cytokines, are increased in human osteoarthritis. The excessive production of nitric oxide inhibits matrix synthesis and promotes its degradation. Furthermore, by reacting with oxidants such as superoxide anion, nitric oxide promotes cellular injury and renders the chondrocyte susceptible to cytokine-induced apoptosis. PGE(2) exerts anabolic and catabolic effects on chondrocytes, depending on the microenvironment and physiologic condition. The increased expression of inducible NOS (iNOS) and cyclo-oxygenase-2 (COX-2) in OA chondrocytes is largely due to the increased expression of pro-inflammatory cytokines, particularly IL-1, which act in an autocrine/paracrine fashion to perpetuate a catabolic state that leads to progressive destruction of articular cartilage. The initiating factors for the production of inflammatory mediators include altered biomechanical forces; their continued production may be augmented by an increase in extracellular matrix proteins acting through ligation of surface integrins.
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Articular cartilage of patients with osteoarthritis shows features of senescence, including increased nitric oxide and pro-inflammatory cytokines, p16, activated DNA damage response, ROS secretion and SA-β-Gal activity.
“Articular cartilage of patients with OA shows features of senescence, including increased expression of nitric oxide, pro-inflammatory cytokines, particularly IL-1β [8]; p16 [9]; activated DNA damage response; ROS secretion and SA-β-Gal activity [10].”
From Fibrates as drugs with senolytic and autophagic activity for osteoarthritis therapy (2019) · cites this paper as [8]
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- Authors
- Abramson, S. B., Attur, M., Amin, A. R., & Clancy, R.
- Affiliations
- NYU Langone Health (US)
- Venue
- Current Rheumatology Reports
- Published
- 2001-12
- Volume
- 3
- Issue
- 6
- Pages
- 535-541
- ISSN
- 1523-3774 (ISSN-L)
- 1534-6307
- OpenAlex
- W2081577257
- Cited by
- 261
- References
- 63
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 9 · 2020: 18 · 2019: 15 · 2018: 14 · 2017: 13 · 2016: 15 · 2015: 10 · 2014: 12 · 2013: 13 · 2012: 12
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Rheumatology Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Keywords
- osteoarthritis, nitric oxide, articular chondrocytes, inflammatory mediators, inducible nitric oxide synthase, cyclooxygenase-2, prostaglandin E2, interleukin-1, inflammatory cytokines, apoptosis, cartilage degeneration, extracellular matrix, integrins, biomechanical forces, autocrine and paracrine signaling
- MeSH terms
- Cartilage, Articular, Humans, Nitric Oxide, Osteoarthritis, Cytokines, Inflammation Mediators, Nitric Oxide Synthase, Nitric Oxide Synthase Type II
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