1H-Nuclear Magnetic Resonance Studies of Human Synovial Fluid in Arthritic Disease States as An Aid to Confirming Metabolic Activity in the Synovial Cavity

Duffy, J. M.; Grimshaw, James; Guthrie, David J. S.; Mcnally, G. M.; Mollan, Rab; Spedding, P.L.; Trocha-Grimshaw, Jadwiga; Walker, Brian; Walsh, Erin P.

doi:10.1042/cs0850343

Cited by 23 publications

(18 citation statements)

References 6 publications

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“…Of those, we found that only HAS2 mRNA was expressed in bovine articular chondrocytes [15]. Increased concentrations of HA have been found at sites of chronic infl ammation [16], and the antioxidative effect of HA has recently been reported [17,18]. The purpose of the present study was to determine if hypoxia induces HA synthesis by chondrocytes, and, if so, whether the hypoxia-induced HA synthesis is regulated by NO.…”

Section: Introductionmentioning

confidence: 90%

Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide

et al. 2006

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Section: Introductionmentioning

confidence: 90%

Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide

et al. 2006

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“…Increased concentrations of HA have been found at sites of chronic inflammation (20,21), and when the size of this HA has been studied the molecular weight range has been found to include lower molecular weight species (22,23). Chronically inflamed tissues also contain elevated levels of the soluble, chemotactic cytokines known as chemokines (24 -31), many of which are major products of activated macrophages.…”

Section: Nitric Oxide (No ⅐ )mentioning

confidence: 99%

Hyaluronan Fragments Induce Nitric-oxide Synthase in Murine Macrophages through a Nuclear Factor κB-dependent Mechanism

McKee

Lowenstein

Horton

et al. 1997

Journal of Biological Chemistry

270

166

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Activated macrophages play a critical role in controlling chronic tissue inflammation through the release of a variety of mediators including cytokines, chemokines, growth factors, active lipids, reactive oxygen, and nitrogen species. The mechanisms that regulate macrophage activation in chronic inflammation are poorly understood. A hallmark of chronic inflammation is the turnover of extracellular matrix components, and recent work has suggested that interactions with the extracellular matrix can exert important influences on macrophage effector functions. We have examined the effect of low molecular weight fragments of the extracellular matrix glycosaminoglycan hyaluronan (HA) on the induction of nitric-oxide synthase (iNOS) in macrophages. We found that HA fragments induce iNOS mRNA, protein and activity alone, and markedly synergize with interferon-␥ to induce iNOS gene expression in murine macrophages. In addition, we found that resident tissue alveolar macrophages respond minimally, but inflammatory alveolar macrophages exhibit a marked induction in iNOS expression in response to HA fragments. Finally, we demonstrate that the mechanism of HA fragment-induced expression of iNOS requires activation of the transcriptional regulator nuclear factor B. These data support the hypothesis that HA may be an important regulator of macrophage activation at sites of chronic tissue inflammation. Nitric oxide (NO ⅐ )1 mediates a number of the host defense functions of activated macrophages, including antimicrobial and tumoricidal activity (1-7). NO ⅐ and its metabolites have also been implicated in the pathogenesis of the tissue damage associated with acute and chronic inflammation (8 -12). Macrophages generate NO ⅐ from the guanido moiety of L-arginine through a reaction catalyzed by the inducible form of nitricoxide synthase (2). In contrast to the constitutive, calcium-dependent form of the enzyme found in the central nervous system and endothelial cells, iNOS can be induced by numerous immune stimuli. Maximal, synergistic iNOS induction occurs in response to the combination of a priming stimulus, such as IFN␥, and a triggering stimulus, examples of which include LPS, tumor necrosis ␣, and interleukin-2 (6, 13, 14).Hallmarks of chronic inflammation include the accumulation of activated macrophages and of macrophage-derived mediators. However, the mechanisms of macrophage activation in this setting have not been clearly defined. The ECM undergoes increased degradation and turnover during inflammation, and fragments of ECM molecules have been found to possess biological activities distinct from their parent compounds (15-17). It has therefore been proposed that ECM fragments may be responsible for activating macrophages that infiltrate chronically inflamed tissues (18). We have recently demonstrated that fragments of the ECM component HA can bind to macrophages and induce the expression of a number of inflammatory genes (32), suggesting that HA fragments may be capable of activating macrophages at non-infectious sites of...

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“…Our results showed that the enhanced HA concentration with cyclic strain was due to an increase of HAS2 in the chondrocytes. Increased concentrations of HA have been found at sites of chronic inflammation (27), and lower molecular weight species of HA were exhibited in synovial fluid in arthritis (28). HA has numerous roles in the activation and modulation of the inflammatory response, including the antioxidant scavenging of ROS derived from polymorphonuclear leukocytes (29).…”

mentioning

confidence: 99%

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

Yamazaki¹,

Fukuda²,

Matsukawa³

et al. 2003

Arthritis & Rheumatism

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Objective. We have previously demonstrated that reactive oxygen species (ROS) are involved in cartilage degradation. Decreased size of hyaluronan (HA), the major macromolecule in synovial fluid, to which it imparts viscosity, is reported in patients with arthritis. The purpose of this study was to determine the alteration in the molecular weight range of HA as a result of mechanical deformation loaded on the chondrocytes, as well as the involvement of ROS in this action.Methods. ROS were generated via the oxidation of hypoxanthine by xanthine oxidase. Cyclic tensile stretch was loaded using a vacuum-operated instrument. Levels of HA were measured using a sandwich enzyme-binding assay. Superoxide dismutase (SOD) activity and ROS were measured using water-soluble tetrazolium and a chemiluminescent probe, respectively.Results. ROS depolymerized HA molecules. Cyclic tensile stretch depolymerized HA and induced ROS. SOD inhibited not only ROS induction but also HA depolymerization caused by the mechanical stress.Conclusion. ROS play an important role in mechanical stress-induced HA depolymerization.

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1H-Nuclear Magnetic Resonance Studies of Human Synovial Fluid in Arthritic Disease States as An Aid to Confirming Metabolic Activity in the Synovial Cavity

Cited by 23 publications

References 6 publications

Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide

Hypoxia-induced hyaluronan synthesis by articular chondrocytes: the role of nitric oxide

Hyaluronan Fragments Induce Nitric-oxide Synthase in Murine Macrophages through a Nuclear Factor κB-dependent Mechanism

Cyclic tensile stretch loaded on bovine chondrocytes causes depolymerization of hyaluronan: Involvement of reactive oxygen species

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