Nitric oxide and proteoglycan turnover in rabbit articular cartilage

Stefanović-Račić, Maja; Möllers, Mareike; Miller, Lauren A.; Evans, Chris

doi:10.1002/jor.1100150318

Cited by 94 publications

(90 citation statements)

References 24 publications

(2 reference statements)

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“…Perhaps NO is responsible in part for the insensitivity of OA or aging chondrocytes to IGF-1, making that cartilage more susceptible to damage or lack of repair. However, the protective effect of NO with respect to catabolism of proteoglycan in articular cartilage has also been proposed (Stefanovic-Racic, Morales, Taskiran, McIntyre, & Evans, 1996).…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes

Iacob

Knudson

2006

The International Journal of Biochemistry & Cell Biology

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Chondrocyte CD44 receptors anchor hyaluronan to the cell surface, enabling the assembly and retention of proteoglycan aggregates in the pericellular matrix. Hyaluronan-CD44 interactions also provide signaling important for maintaining cartilage homeostasis. Disruption of chondrocyte-hyaluronan contact alters CD44 occupancy, initiating alternative signaling cascades. Treatment with hyaluronan oligosaccharides is one approach to uncouple CD44 receptors from its native ligand, hyaluronan. In bovine articular chondrocytes, treatment with hyaluronan oligosaccharides or purified hyaluronan hexasaccharides induced the production of nitric oxide that mirrored nitric oxide production following interleukin-1 treatment. In contrast, 120 and 1260 kDa hyaluronan did not induce production of nitric oxide. Human chondrocytes responded similarly to treatment with hyaluronan or hyaluronan oligosaccharides. Nitric oxide production from chondrocytes was mediated by activation of the inducible nitric oxide synthase, as confirmed by mRNA expression and inhibition of nitric oxide production by diphenyleneiodonium. Cotreatment of chondrocytes with hyaluronan oligosaccharides and interleukin-1 did not demonstrate additive effects. Blocking interleukin-1 receptors with an antagonist did not abolish the production of nitric oxide induced by treatment with hyaluronan oligosaccharides. Moreover, only COS-7 following transfection with a pCD44, not the CD44-null parental cells, responded to treatment with hyaluronan oligosaccharides by releasing nitric oxide. This study demonstrates a novel signaling potential by hyaluronan fragments, in lieu of endogenous hyaluronan-chondrocyte interactions, resulting in the activation of inducible nitric oxide synthase.

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Section: Discussionmentioning

confidence: 99%

Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes

Iacob

Knudson

2006

The International Journal of Biochemistry & Cell Biology

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“…IL-1 exerts strong catabolic effects on cartilage extracellular matrix synthesis (29,38,43,49). These effects are associated with increased production of nitric oxide (NO), a product of NO synthase (NOS) (14,31,37,42,51).…”

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confidence: 99%

Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide

Shin¹,

Fermor²,

Weinberg³

et al. 2003

Journal of Applied Physiology

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. Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide. J Appl Physiol 95: 308-313, 2003. First published March 28, 2003 10.1152/ japplphysiol.00131.2003The meniscus is an intra-articular fibrocartilaginous structure that serves essential biomechanical roles in the knee. With injury or arthritis, the meniscus may be exposed to significant changes in its biochemical and biomechanical environments that likely contribute to the progression of joint disease. The goal of this study was to examine the influence of mechanical stress on matrix turnover in the meniscus in the presence of interleukin-1 (IL-1) and to determine the role of nitric oxide (NO) in these processes. Explants of porcine menisci were subjected to dynamic compressive stresses at 0.1 MPa for 24 h at 0.5 Hz with 1 ng/ml IL-1, and the synthesis of total protein, proteoglycan, and NO was measured. The effects of a nitric oxide synthase 2 (NOS2) inhibitor were determined. Dynamic compression significantly increased protein and proteoglycan synthesis by 68 and 58%, respectively, compared with uncompressed explants. This stimulatory effect of mechanical stress was prevented by the presence of IL-1 but was restored by specifically inhibiting NOS2. Release of proteoglycans into the medium was increased by IL-1 or mechanical compression and further enhanced by IL-1 and compression together. Stimulation of proteoglycan release in response to compression was dependent on NOS2 regardless of the presence of IL-1. These finding suggest that IL-1 may modulate the effects of mechanical stress on extracellular matrix turnover through a pathway that is dependent on NO.

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“…The localization of iNOS protein in fibrotic areas rather than in inflammatory cell aggregates suggests that the expression of iNOS is a secondary event which may be involved in tissue remodelling or scar formation. Although NO has been shown to be involved in pathways that lead to the generation of cartilage-and matrix-degrading enzymes [29,30], there are reports suggesting that NO may also have protective functions by inhibiting catabolic effects of IL-1 on cartilage [31], by suppressing lymphocyte proliferation [32][33][34] and by inhibition of MHC class II expression [35]. In various experimental animal models of arthritis, increased iNOS transcripts or protein have been noted, and in many instances inhibition of NOS activity by chemical compounds has been shown to reduce the severity of arthritis (reviewed in [36]).…”

Section: Discussionmentioning

confidence: 99%

Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus

Lechner

Schütte

Bodungen

et al. 1999

Clinical and Experimental Immunology

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SUMMARYWe have studied the expression of the inducible form of nitric oxide synthase (iNOS) in joints of goats infected with the caprine arthritis encephalitis virus (CAEV). Nitric oxide generated by iNOS is thought to play an important role in the pathogenesis of various types of arthritis, especially rheumatoid arthritis (RA) in humans. Surprisingly, iNOS immunoreactivity was found only in joints of long-term infected goats with severe clinical arthritis, whereas-despite the presence of high numbers of inflammatory cells in the synovial tissue-no iNOS immunoreactivity was detected in mildly arthritic and in shortterm experimentally infected goats. Most iNOS-positive cells expressed neither MHC class II nor CD68, which suggests that they were fibroblast-like synoviocytes. In situ hybridization studies showed that there was no correlation between iNOS immunoreactivity and detectable virus expression in the joint. In addition, infection of macrophages in vitro-the major host cells of CAEV in vivo-did not lead to increased iNOS mRNA expression. In response to stimulation, similar levels of iNOS expression were observed in infected and in uninfected macrophages. These findings suggest that the expression of iNOS is a feature of late-stage chronic arthritis and is not involved in the development of the inflammatory lesions. Both the lack of co-localization of iNOS protein and viral transcripts in the joint and the finding that CAEV does not stimulate the expression of iNOS in vitro further suggest that iNOS is not directly induced by the virus or the anti-viral immune response in the joint, that it may well, however, be involved in tissue remodelling or scar formation.

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Nitric oxide and proteoglycan turnover in rabbit articular cartilage

Cited by 94 publications

References 24 publications

Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes

Hyaluronan fragments activate nitric oxide synthase and the production of nitric oxide by articular chondrocytes

Regulation of matrix turnover in meniscal explants: role of mechanical stress, interleukin-1, and nitric oxide

Inducible nitric oxide synthase is expressed in joints of goats in the late stage of infection with caprine arthritis encephalitis virus

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