Cited by 740Osteoarthritis Treatment and MechanismsRedox biology and oxidative stressAntioxidant Activity and Oxidative Stress

The role of reactive oxygen species in homeostasis and degradation of cartilage

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Henrotin, Y.E, Bruckner, P, Pujol, J.-P.L·2003·Osteoarthritis and Cartilage

Abstract

Objectives The metabolism of cells in articular joint tissues in normal and pathological conditions is subject to a complex environmental control. In addition to soluble mediators such as cytokines and growth factors, as well as mechanical stimuli, reactive oxygen species (ROS) emerge as major factors in this regulation. ROS production has been found to increase in joint diseases, such as osteoarthritis and rheumatoid arthritis, but their role in joint diseases initiation and progression remains questionable.Method This review is focused on the role of ROS, mainly nitric oxide, peroxynitrite and superoxide anion radicals, in the signaling mechanisms implied in the main cellular functions, including synthesis and degradation of matrix components. The direct effects of ROS on cartilage matrix components as well as their inflammatory and immunomodulatory effects are also considered.Results Some intracellular signaling pathways are redox sensitive and ROS are involved in the regulation of the production of some biochemical factors involved in cartilage degradation and joint inflammation. Further, ROS may cause damage to all matrix components, either by a direct attack or indirectly by reducing matrix components synthesis, by inducing apoptosis or by activating latent metalloproteinases. Finally, we have highlighted the uncoupling effect of ROS on tissue remodeling and synovium inflammation, suggesting that antioxidant therapy could be helpful to treat structural changes but not to relieve symptoms.Conclusions This review of the literature supports the concept that ROS are not only deleterious agents involved in cartilage degradation, but that they also act as integral factors of intracellular signaling mechanisms. Further investigation is required to support the concept of antioxidant therapy in the management of joint diseases.

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  1. Moulton PJ, Goldring MB, Hancock JT. NADPHoxi- dase of chondrocytes contains an isoform of gp91phox subunit. Biochem J 1998;329:449-51.
  2. Henrotin Y, Deberg M, Christgau S, Henriksen D, Seidel L, Reginster J-Y. Type II collagen derived fragment (Coll2-1) is a new marker predictive of osteoarthritic progression. Osteoporos Int 2002;13: S17 (O21).
  3. Lo YYC, Conquer JA, Grinstein S, Cruz TF. Interleukin-1 induction of c-fos and collagenase expression in articular chondrocytes: involvement of reactive oxygen species. J Cell Biochem 1998;69: 19-29.
  4. Blanco FJ, Guitan R, Vasquez-Martul E, de Torro FJ, Galdo F. Osteoarthritis chondrocyte die by apoptosis: a possible pathway for osteoarthritis pathology. Arthritis Rheum 1998;41:284-9.
  5. Horton WE Jr, Feng L, Adam C. Chondrocyte apopto- sis in development, ageing and disease. Matrix Biol 1998;17:107-15.
  6. Hashimoto S, Takahashi K, Amiel D, Coutts RGD, Lotz M. Chondrocyte apoptosis and nitric oxide production during experimental induced osteoarthritis. Arthritis Rheum 1998;41:1266-74.
  7. Mathy-Hartert M, Martin G, Deby-Dupont G, Pujol JP, Reginster JY, Henrotin Y. Reactive oxygen species down-regulate pro-inflammatory gene expression by human chondrocytes. Inflamm Res 2003;52:111-8.
  8. Pelletier JP, Jovanovic D, Lascau-Coman V, Fernandes JC, Manning PT, Connor JR, et al. Selec- tive inhibition of inducible nitric oxide synthase reduces progression of experimental osteoarthritis in vivo. Arthritis Rheum 2000;43:1290-9.
  9. De Bandt M, Grossin M, Weber AJ, Chopin M, Elbim C, Pla M, et al. Suppression of arthritis and protection from bone destruction by treatment with TNP-470/ AGM-1470 in a transgenic mouse model of rheuma- toid arthritis. Arthritis Rheum 2000;43:2056-63.
  10. Greewald RA, Moy WW. Inhibition of collagen gelation by action of superoxide radicals. Arthritis Rheum 1979;22:251-9.
  11. Y. E. Henrotin et al.: Reactive oxygen species in cartilage degradation wild-type mice with unabated joint inflammation. Arthritis Rheum 1998;41:634-46.
  12. Veihelmann A, Landes J, Hofbauer A, Dorger M, Refior HJ, Messmer K, et al. Exacerbation of antigen- induced arthritis in inducible nitric oxide synthase- deficient mice. Arthritis Rheum 2001;44:1420-7.
  13. Milner JM, Elliott SF, Cawston TE. Activation of procol- lagenases is a key control point in cartilage collagen degradation. Interaction of serine and metallopro- teinases pathways. Arthritis Rheum 2001;44: 2084-96.
  14. Rowan AD, Koshy PJT, Shingleton WD, Degnan BA, Heath JK, Vernallis AB, et al. Synergic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum 2001;44:1620-32.

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Authors
Henrotin, Y. E., Bruckner, P., & Pujol, J.-P. L.
Affiliations
  • University of Liège (BE)
  • Université de Caen Normandie (FR)
Corresponding author
Henrotin, Y.E
Venue
Osteoarthritis and Cartilage
Publisher
Elsevier BV
Published
2003-10
Volume
11
Issue
10
Pages
747-755
ISSN
1063-4584 (ISSN-L)
OpenAlex
W2044924856
Cited by
740
References
82
Citations by year
2026: 15 · 2025: 29 · 2024: 30 · 2023: 35 · 2022: 34 · 2021: 37 · 2020: 39 · 2019: 35 · 2018: 45 · 2017: 36 · 2016: 32 · 2015: 33 · 2014: 35 · 2013: 34 · 2012: 45
FWCI
3.61
Type
journal article
Language
en
Open access
Locations
  • Osteoarthritis and Cartilage (publishedVersion)
  • PubMed (publishedVersion)
  • ORBi (University of Liège) (submittedVersion)
Funders
UCB Pharma
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Keywords
reactive oxygen species, cartilage degeneration, cartilage homeostasis, nitric oxide, peroxynitrite, superoxide, redox signaling, joint inflammation, synovium, matrix metalloproteinases, apoptosis, antioxidant therapy, osteoarthritis, rheumatoid arthritis
MeSH terms
Cartilage, Articular, Extracellular Matrix, Homeostasis, Humans, Osteoarthritis, Oxidation-Reduction, Synovial Membrane, Signal Transduction, Cytokines, Apoptosis, Reactive Oxygen Species, Chondrocytes, Metalloproteases

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