Nitric oxide sustains nuclear factor kappaB activation in cytokine-stimulated chondrocytes

Clancy, Robert M.; Gomez, Paul; Abramson, Steven B.

doi:10.1016/j.joca.2004.04.003

Cited by 80 publications

(62 citation statements)

References 23 publications

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“…The activation of p38 MAP kinase and NF-κB nuclear translocation by HA oligos are in common with the stimulation of NO due to treatment of cells with IL-1 (Badger et al, 1998;Clancy et al, 2004;Mendes et al, 2001). In this study we demonstrated that this similarity was not due to HA oligos -induced autocrine release of endogenous IL-1 (Fig.…”

Section: Discussionsupporting

confidence: 73%

“…Using a protein-DNA array screen and EMSA analyses we have also observed the induction of NF-κB in bovine articular chondrocytes treated with HA oligos as well as purified HA 6 (Ohno et al, 2005). Given that increased activity of NF-κB is closely associated with iNOS induction (Clancy, Gomez, & Abramson, 2004) these results suggest a possible mechanism for the increases in the iNOS and NO production following HA oligos stimulation. As well, HA oligos induced iNOS expression in BV-2 microglia mediated by a p38 MAP kinase-dependent pathway (Wang et al, 2004).…”

Section: Discussionmentioning

confidence: 67%

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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: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 67%

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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“…The reason for the slightly higher incidence in the AZD3582 375 mg and 750 mg twice a day groups than in the naproxen recipients is not known. Although inducible nitric oxide may alter cartilage metabolism by a number of possible mechanisms (29), the effects of exogenous nitric oxide or nitric oxide in the presence of NSAIDs (30) are not known; no evaluation of cartilage integrity was undertaken in this study.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the COX‐inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of Osteoarthritis of the knee

Schnitzer¹,

Kivitz²,

Lipetz³

et al. 2005

Arthritis & Rheumatism

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Objective. To compare the efficacy, safety, and tolerability of AZD3582 with that of rofecoxib, naproxen, and placebo in patients with osteoarthritis (OA) of the knee, and to define the dosage of AZD3582 (125 mg, 375 mg, and 750 mg twice a day) that is noninferior in efficacy to rofecoxib. Methods. A double-blind study of 672 patients with OA of the knee was conducted. Patients who experienced increased pain on withdrawal of analgesia were randomized to receive AZD3582 125 mg, 375 mg, or 750 mg twice a day; rofecoxib 25 mg once a day; naproxen 500 mg twice a day; or placebo for 6 weeks. Efficacy, tolerability, and safety were monitored throughout the study. The primary variable was the change in Western Ontario and McMaster Universities Osteoarthritis Index pain subscale from baseline to the mean of weeks 4 and 6, comparing AZD3582 with placebo for superiority and with rofecoxib for noninferiority using a predefined margin of 10 mm.

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“…In vivo, however, it is likely that TNF-α as one of catabolic cytokines is produced by cartilage in osteoarthritis that could function as effectors of chondrocyte apoptosis (Fernandes et al, 2002). Production of TNF-α results in high level of nitric oxide (NO), which in turn induces chondrocyte apoptosis (Clancy et al, 2004). Our previous study showed that T-2 toxin increased the production of TNF-α (Li et al, 2008).…”

Section: Rt-pcr Detection Of Bax Bcl-xl Bcl-2 P53 Fas and Caspasementioning

confidence: 99%

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

Chen

Cao

Chu

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To investigate the effects of T-2 toxin on expressions of Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 on human chondrocytes. Methods: Human chondrocytes were treated with T-2 toxin (1~20 ng/ml) for 5 d. Fas, p53 and other apoptosis-related proteins such as Bax, Bcl-2, Bcl-xL, caspase-3 were determined by Western blot analysis and their mRNA expressions were determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Increases in Fas, p53 and the pro-apoptotic factor Bax protein and mRNA expressions and a decrease of the anti-apoptotic factor Bcl-xL were observed in a dose-dependent manner after exposures to 1~20 ng/ml T-2 toxin, while the expression of the anti-apoptotic factor Bcl-2 was unchanged. Meanwhile, T-2 toxin could also up-regulate the expressions of both pro-caspase-3 and caspase-3 in a dose-dependent manner. Conclusion: These data suggest a possible underlying molecular mechanism for T-2 toxin to induce the apoptosis signaling pathway in human chondrocytes by regulation of apoptosis-related proteins.

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Nitric oxide sustains nuclear factor kappaB activation in cytokine-stimulated chondrocytes

Cited by 80 publications

References 23 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

Comparison of the COX‐inhibiting nitric oxide donator AZD3582 and rofecoxib in treating the signs and symptoms of Osteoarthritis of the knee

T-2 toxin-induced apoptosis involving Fas, p53, Bcl-xL, Bcl-2, Bax and caspase-3 signaling pathways in human chondrocytes

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