Differential roles of nitric oxide and oxygen radicals in chondrocytes affected by osteoarthritis and rheumatoid arthritis

2001 ◽  
Vol 101 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Ilaria MAZZETTI ◽  
Brunella GRIGOLO ◽  
Lia PULSATELLI ◽  
Paolo DOLZANI ◽  
Tania SILVESTRI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Cartilage Damage ◽  
Organ Donors ◽  
Oxygen Species ◽  
Radical Oxygen Species ◽  
Oxygen Intermediates

Osteoarthritis and rheumatoid arthritis are characterized by focal loss of cartilage due to an up-regulation of catabolic pathways, induced mainly by pro-inflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor α (TNFα). Since reactive oxygen species are also involved in this extracellular-matrix-degrading activity, we aimed to compare the chondrocyte oxidative status responsible for cartilage damage occurring in primarily degenerative (osteoarthritis) and inflammatory (rheumatoid arthritis) joint diseases. Human articular chondrocytes were isolated from patients with osteoarthritis or rheumatoid arthritis, or from multi-organ donors, and stimulated with IL-1β and/or TNFα. We evaluated the oxidative stress related to reactive nitrogen and oxygen intermediates, measuring NO2- as a stable end-product of nitric oxide generation and superoxide dismutase as an antioxidant enzyme induced by radical oxygen species. We found that cells from patients with osteoarthritis produced higher levels of NO2- than those from patients with rheumatoid arthritis. In addition, IL-1β was more potent than TNFα in inducing nitric oxide in both arthritides, and TNFα alone was almost ineffective in cells from rheumatoid arthritis patients. We also observed that the intracellular content of copper/zinc superoxide dismutase (Cu/ZnSOD) was always lower in rheumatoid arthritis chondrocytes than in those from multi-organ donors, whereas no differences were found in intracellular manganese SOD (MnSOD) or in supernatant Cu/ZnSOD and MnSOD levels. Moreover, intracellular MnSOD was up-regulated by cytokines in osteoarthritis chondrocytes. In conclusion, our results suggest that nitric oxide may play a major role in altering chondrocyte functions in osteoarthritis, whereas the harmful effects of radical oxygen species are more evident in chondrocytes from patients with rheumatoid arthritis, due to an oxidant/antioxidant imbalance.

scholarly journals Redox Status in Women with Rheumathoid Arthritis

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Aleksandra Vranic ◽  
Aleksandra Antovic ◽  
Nevena Draginic ◽  
Marijana Andjic ◽  
Marko Ravic ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Cartilage Damage ◽  
Thiobarbituric Acid ◽  
Antioxidant Defense System ◽  
Redox Status ◽  
Female Population

Abstract The aim of this study was to assess oxidative status and to set baseline characteristics for female population with established rheumatoid arthritis. Total of 42 patients with rheumatoid arthritis and 48 age- and sex-matched controls were included in the study. Clinical examination was performed and assessed disease activity. Peripheral blood samples were used for all the assays. The markers of oxidative stress were assessed, including plasma levels of index of lipid peroxidation - thiobarbituric acid reactive substances, hydrogen peroxide, superoxide anion radical, nitrites and activity of superoxide dismutase, catalase and reduced glutathione levels as antioxidant parameters. In the patients group, levels of hydrogen peroxide and index of lipid peroxidation were higher than in controls. Patients with rheumatoid arthritis had decreased superoxide dismutase and catalase activity compared to healthy subjects. Interestingly, controls had higher levels of nitrites compared to patients. Patients showed a marked increase in reactive oxygen species formation and lipid peroxidation as well as decrease in the activity of antioxidant defense system leading to oxidative stress which may contribute to tissue and cartilage damage and hence to the chronicity of the disease.

Nitric oxide level and superoxide dismutase activity in serum of patients with rheumatoid arthritis

2003 ◽  
Vol 15 (4) ◽  
pp. 429-434 ◽  
Author(s):  
Seyithan Taysi ◽  
Zuhal Umudum ◽  
Refik Ali Sari ◽  
Sevinc Kuskay ◽  
Nuri Bakan
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Superoxide Dismutase Activity ◽  
Nitric Oxide Level

scholarly journals Neuroprotective effects of thymoquinone against spinal cord ischemia-reperfusion injury by attenuation of inflammation, oxidative stress, and apoptosis

2016 ◽  
Vol 24 (6) ◽  
pp. 949-959 ◽  
Author(s):  
Emre Cemal Gökce ◽  
Ramazan Kahveci ◽  
Aysun Gökce ◽  
Berker Cemil ◽  
Nurkan Aksoy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Superoxide Dismutase ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Injury Group ◽  
Factor Α ◽  
Necrosis Factor

OBJECTIVE Ischemia-reperfusion (I/R) injury of the spinal cord following thoracoabdominal aortic surgery remains the most devastating complication, with a life-changing impact on the patient. Thymoquinone (TQ), the main constituent of the volatile oil from Nigella sativa seeds, is reported to possess strong antioxidant, antiinflammatory, and antiapoptotic properties. This study investigated the effects of TQ administration following I/R injury to the spinal cord. METHODS Thirty-two rats were randomly allocated into 4 groups. Group 1 underwent only laparotomy. For Group 2, aortic clip occlusion was introduced to produce I/R injury. Group 3 was given 30 mg/kg of methylprednisolone intraperitoneally immediately after the I/R injury. Group 4 was given 10 mg/kg of TQ intraperitoneally for 7 days before induction of spinal cord I/R injury, and administration was continued until the animal was euthanized. Locomotor function (Basso, Beattie, and Bresnahan scale and inclined plane test) was assessed at 24 hours postischemia. Spinal cord tissue samples were harvested to analyze tissue concentrations of malondialdehyde, nitric oxide, tumor necrosis factor–α, interleukin-1, superoxide dismutase, glutathione-peroxidase, catalase, and caspase-3. In addition, histological and ultrastructural evaluations were performed. RESULTS Thymoquinone treatment improved neurological outcome, which was supported by decreased levels of oxidative products (malondialdehyde and nitric oxide) and proinflammatory cytokines (tumor necrosis factor–α and interleukin-1), increased activities of antioxidant enzymes (superoxide dismutase, glutathione-peroxidase, and catalase), as well as reduction of motor neuron apoptosis. Light microscopy and electron microscopy results also showed preservation of tissue structure in the treatment group. CONCLUSIONS As shown by functional, biochemical, histological, and ultrastructural analysis, TQ exhibits an important protective effect against I/R injury of the spinal cord.

scholarly journals Antioxidants and fatty acids in the amelioration of rheumatoid arthritis and related disorders

2001 ◽  
Vol 85 (3) ◽  
pp. 251-269 ◽  
Author(s):  
L. Gail Darlington ◽  
Trevor W. Stone
Keyword(s):  
Rheumatoid Arthritis ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Fatty Acids ◽  
Free Radicals ◽  
Nitric Oxide Synthase ◽  
Prostaglandin E ◽  
Oxygen Species ◽  
Beneficial Effects ◽  
Oxide Synthase

The generation of reactive oxygen species (free radicals) is an important factor in the development and maintenance of rheumatoid arthritis in humans and animal models. One source of free radicals is nitric oxide produced within the synoviocytes and chondrocytes and giving rise to the highly toxic radical peroxynitrite. Several cytokines, including tumour necrosis factor-α (TNFα) are involved in the formation of free radicals, partly by increasing the activity of nitric oxide synthase. Indeed, nitric oxide may mediate some of the deleterious effects of cytokines on bone resorption. Aspirin, tetracyclines, steroids and methotrexate can suppress nitric oxide synthase. Dietary antioxidants include ascorbate and the tocopherols and beneficial effects of high doses have been reported especially in osteoarthritis. There is also evidence for beneficial effects of β-carotene and selenium, the latter being a component of the antioxidant enzyme glutathione peroxidase. The polyunsaturated fatty acids (PUFA) include then-3 compounds, some of which are precursors of eicosanoid synthesis, and then-6 group which can increase formation of the pro-inflammatory cytokines TNFα and interleukin-6, and of reactive oxygen species. Some prostaglandins, however, suppress cytokine formation, so thatn-3 PUFA often oppose the inflammatory effects of somen-6-PUFA. γ-linolenic acid (GLA) is a precursor of prostaglandin E1, a fact which may account for its reported ability to ameliorate arthritic symptoms. Fish oil supplements, rich inn-3 PUFA such as eicosapentaenoic acid have been claimed as beneficial in rheumatoid arthritis, possibly by suppression of the immune system and its cytokine repertoire. Some other oils of marine origin (e.g. from the green-lipped mussel) and a range of vegetable oils (e.g. olive oil and evening primrose oil) have indirect anti-inflammatory actions, probably mediated via prostaglandin E1. Overall, there is a growing scientific rationale for the use of dietary supplements as adjuncts in the treatment of inflammatory disorders such as rheumatoid arthritis and osteoarthritis.

scholarly journals Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giovanna Nalesso ◽  
Anne-Sophie Thorup ◽  
Suzanne Elizabeth Eldridge ◽  
Anna De Palma ◽  
Amanpreet Kaur ◽  
...  
Keyword(s):  
Medial Meniscus ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Cartilage Damage ◽  
Regenerative Processes ◽  
Cartilage Homeostasis ◽  
Calmodulin Kinase ◽  
Wnt Ligands ◽  
Pharmacological Blockade

AbstractWNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes.

Asiatic Acid Attenuates Osteoarthritis by Regulating NF-κB Signaling Pathway in Chondrocytes

2020 ◽  
Author(s):  
Zhengmeng Yang ◽  
Lu Feng ◽  
Xiaoting Zhang ◽  
Weiping Lin ◽  
Bin Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Articular Chondrocytes ◽  
Cartilage Damage ◽  
Luciferase Assay ◽  
No Production ◽  
Asiatic Acid ◽  
Dependent Manner ◽  
Cox 2 ◽  
Dose Dependent

Abstract Background: Natural small molecules have become more attractive as alternatives to non-steroidal anti-inflammatory drugs in osteoarthritis (OA) treatments. This study aims to investigate the effects of Asiatic acid (AA) on OA in chondrocytes and the surgery-induced OA animal model. Methods: Cytotoxicity of AA in primary rat articular chondrocytes was determined. Chondrocytes were pretreated with AA at the safe concentrations and subsequently treated with IL-1β. The production of inflammatory mediators including nitric oxide (NO), nitric oxide synthase (iNOS), as well as cyclooxygenase (COX)-2, and the expression of chondrogenic and hypertrophic markers including Sox 9, Aggrecan, Col 2a1, and matrix metalloproteinase-13 (MMP13) in the cells were measured. The effect of AA on nuclear factor-kappa B (NF-κB) signaling pathway was further determined by dual luciferase assay and western blot. The surgery-induced OA animals were treated with AA or saline for 6 weeks. The pathological changes in the affected joints were measured by micro-CT and histological analysis. Results: We found a broad safety spectrum of AA from 0 to 25 μM. A dose-dependent inhibitory effect of AA on NO production, as well as iNOS and COX-2 expression were found. Meanwhile, AA promoted chondrogenesis and inhibited hypertrophy in chondrocyte treated with IL-1β. In addition, AA inhibited NF-κB signaling pathway with a dose-dependent manner. Furthermore, results from animal study revealed that AA prevented articular cartilage damage as well as subchondral bone remodeling in the surgery-induced OA animal.

scholarly journals Cloning, characterization, and expression of a cDNA encoding an inducible nitric oxide synthase from the human chondrocyte

1993 ◽  
Vol 90 (23) ◽  
pp. 11419-11423 ◽  
Author(s):  
I G Charles ◽  
R M Palmer ◽  
M S Hickery ◽  
M T Bayliss ◽  
A P Chubb ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cdna Clone ◽  
Articular Chondrocytes ◽  
Interleukin 1 ◽  
Cell Types ◽  
No Synthase ◽  
Human Chondrocyte ◽  
Oxide Synthase ◽  
Different Cell Types ◽  
Inducible Nitric Oxide

Incubation of human articular chondrocytes with interleukin 1 beta results in the time-dependent expression of nitric oxide (NO) synthase. We report here the isolation of a cDNA clone which encodes a protein of 1153 amino acids with a molecular mass of 131,213 Da and a calculated isoelectric point of 7.9. CHO cells transfected with a plasmid harboring this cDNA clone expressed NO synthase activity that was inhibited by some L-arginine analogues. The deduced amino acid sequence of the human chondrocyte inducible NO synthase shows 51% identity and 68% similarity with the endothelial NO synthase and 54% identity and 70% similarity with the neuronal NO synthase. The similarity (88%) between the human chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage suggests that the inducible class of enzyme is conserved between different cell types and across species.

scholarly journals Cu,Zn Superoxide Dismutase of Mycobacterium tuberculosis Contributes to Survival in Activated Macrophages That Are Generating an Oxidative Burst

2001 ◽  
Vol 69 (8) ◽  
pp. 4980-4987 ◽  
Author(s):  
Debra L. Piddington ◽  
Ferric C. Fang ◽  
Tracey Laessig ◽  
Andrea M. Cooper ◽  
Ian M. Orme ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Mycobacterium Tuberculosis ◽  
Oxidative Burst ◽  
Reactive Oxygen ◽  
Binding Motif ◽  
Oxygen Species ◽  
Activated Macrophages ◽  
Oxygen Intermediates ◽  
Ifn Γ

ABSTRACT Macrophages produce reactive oxygen species and reactive nitrogen species that have potent antimicrobial activity. Resistance to killing by macrophages is critical to the virulence ofMycobacterium tuberculosis. M. tuberculosis has two genes encoding superoxide dismutase proteins, sodA andsodC. SodC is a Cu,Zn superoxide dismutase responsible for only a minor portion of the superoxide dismutase activity ofM. tuberculosis. However, SodC has a lipoprotein binding motif, which suggests that it may be anchored in the membrane to protect M. tuberculosis from reactive oxygen intermediates at the bacterial surface. To examine the role of the Cu,Zn superoxide dismutase in protecting M. tuberculosis from the toxic effects of exogenously generated reactive oxygen species, we constructed a null mutation in thesodC gene. In this report, we show that theM. tuberculosis sodC mutant is readily killed by superoxide generated externally, while the isogenic parentalM. tuberculosis is unaffected under these conditions. Furthermore, the sodC mutant has enhanced susceptibility to killing by gamma interferon (IFN-γ)-activated murine peritoneal macrophages producing oxidative burst products but is unaffected by macrophages not activated by IFN-γ or by macrophages from respiratory burst-deficient mice. These observations establish that the Cu,Zn superoxide dismutase contributes to the resistance of M. tuberculosisagainst oxidative burst products generated by activated macrophages.

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