Enhanced Breakdown of Bovine Articular Cartilage Proteoglycans by Conditioned Synovial Medium in Vitro:<i>The Effect of Glucocorticoids and Protein Synthesis Inhibitors</i>

Klämfeldt, Agneta; Jones, Ian; McGuire, Mary B.

doi:10.3109/03009748209098196

Cited by 10 publications

(5 citation statements)

References 17 publications

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“…Furthermore, our study supports previous reports on oxygen-independent cartilage destruction evoked by neutrophils or conditioned synovial media in vitro. 50,51 We previously showed that endogenous IL-1 suppresses chondrocyte GAG synthesis and this contributes significantly to articular cartilage damage seen during experimental arthritis. 52 NO-mediated the suppression of GAG synthesis by during arthritis.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of NADPH Oxidase Components p47phox and gp91phox Caused Granulomatous Synovitis and Increased Connective Tissue Destruction in Experimental Arthritis Models

Loo¹,

Bennink²,

Arntz³

et al. 2003

The American Journal of Pathology

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Recent studies indicated that the nicotinamide dinucleotide phosphate oxidase (NADPH) oxidase-derived oxygen radicals plays a deleterious role in arthritis. To study this in more detail, gonarthritis was induced in NADPH oxidase-deficient mice. Mice received an intraarticular injection of either zymosan, to elicit an irritant-induced inflammation, or poly-L-lysine coupled lysozyme, to evoke an immune-complex mediated inflammation in passively immunized mice. In contrast to wild-type mice, arthritis elicited in both p47phox ؊/؊ and gp91 ؊/؊ mice showed more severe joint inflammation, which developed into a granulomatous synovitis. Treatment with either Zileuton or cobra venom factor showed that the chemokines LTB4 and complement C3 were not the driving force behind the aggravated inflammation in these mice. Arthritic NADPH oxidase-deficient mice showed irreversible cartilage damage as judged by the enhanced aggrecan VDIPEN expression, and chondrocyte death. Neutrophils and other myeloid cells produce superoxide as part of their bacterial killing. The nicotinamide dinucleotide phosphate (NADPH) oxidase multicomponent enzyme system catalyzes the production of superoxide and the active central role plays the transmembrane cytochrome b558 which is compromised of two subunits, gp91phox and p22phox. P47phox is the cytosolic component of NADPH oxidase complex that translocates to the membrane and associates with cytochrome b556 to form the active complex that catalyzes the reduction of oxygen to superoxide at the expense of NADPH.

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Section: Discussionmentioning

confidence: 99%

Deficiency of NADPH Oxidase Components p47phox and gp91phox Caused Granulomatous Synovitis and Increased Connective Tissue Destruction in Experimental Arthritis Models

Loo¹,

Bennink²,

Arntz³

et al. 2003

The American Journal of Pathology

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“…ROS can cleave collagen (5) and proteoglycans (6, 7), activate MMPs (8), and modulate signaling pathways (9), as well as alter cellular synthetic activity (10) and chondrocyte apoptosis (11). Because ROS are evanescent and difficult to measure directly in vivo, the evidence for their ability to produce damage in cartilage and for their association with arthritis is indirect.…”

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confidence: 99%

Extracellular superoxide dismutase and oxidant damage in osteoarthritis

Regan¹,

Flannelly²,

Bowler³

et al. 2005

Arthritis & Rheumatism

126

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Objective. To use human cartilage samples and a mouse model of osteoarthritis (OA) to determine whether extracellular superoxide dismutase (EC-SOD) is a constituent of cartilage and to evaluate whether there is a relationship between EC-SOD deficiency and OA.Methods. Samples of human cartilage were obtained from femoral heads at the time of joint replacement surgery for OA or femoral neck fracture. Samples of mouse tibial cartilage obtained from STR/ort mice and CBA control mice were compared at 5, 15, and 35 weeks of age. EC-SOD was measured by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry techniques. Real-time quantitative reverse transcription-polymerase chain reaction was used to measure messenger RNA for EC-SOD and for endothelial cell, neuronal, and inducible nitric oxide synthases. Nitrotyrosine formation was assayed by Western blotting in mouse cartilage and by fluorescence immunohistochemistry in human cartilage.Results. Human articular cartilage contained large amounts of EC-SOD (mean ؎ SEM 18.8 ؎ 3.8 ng/gm wet weight of cartilage). Cartilage from patients with OA had an ϳ4-fold lower level of EC-SOD compared with cartilage from patients with hip fracture. Young STR/ort mice had decreased levels of EC-SOD in tibial cartilage before histologic evidence of disease occurred, as well as significantly more nitrotyrosine formation at all ages studied.Conclusion. EC-SOD, the major scavenger of reactive oxygen species in extracellular spaces, is decreased in humans with OA and in an animal model of OA. Our findings suggest that inadequate control of reactive oxygen species plays a role in the pathophysiology of OA.

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“…et al., 1956;Lucy et al, 1961;Jubb & Fell, 1980), bacterial lipopolysaccharides (Jasin, 1984;Morales et al, 1984), and products of cultured synovial (Fell & Jubb, 1977;Dingle et al, 1979;Steinberg et al, 1979;Pilsworth & Saklatvala, 1983;Klamfeldt et al, 1982) and mononuclear cells (Saklatvala & Sarsfield, 1982;Jasin & Dingle, 1981).…”

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confidence: 99%

Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro

Tyler¹

1985

Biochemical Journal

146

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The degradation of proteoglycan was examined in cultured slices of pig articular cartilage. Pig leucocyte catabolin (10 ng/ml) was used to stimulate the chondrocytes and induce a 4-fold increase in the rate of proteoglycan loss from the matrix for 4 days. Material in the medium of both control and depleted cultures was mostly a degradation product of the aggregating proteoglycan. It was recovered as a very large molecule slightly smaller than the monomers extracted with 4M-guanidinium chloride and lacked a functional hyaluronate binding region. The size and charge were consistent with a very limited cleavage or conformational change of the core protein near the hyaluronate binding region releasing the C-terminal portion of the molecule intact from the aggregate. The 'clipped' monomer diffuses very rapidly through the matrix into the medium. The amount of proteoglycan extracted with 4M-guanidinium chloride decreased during culture from both the controls and depleted cartilage, and the average size of the molecules initially remained the same. However, the proportion of molecules with a smaller average size increased with time and was predominant in explants that had lost more than 70% of their proteoglycan. All of this material was able to form aggregates when mixed with hyaluronate, and glycosaminoglycans were the same size and charge as normal, indicating either that the core protein had been cleaved in many places or that larger molecules were preferentially released. A large proportion of the easily extracted and non-extractable proteoglycan remained in the partially depleted cartilage and the molecules were the same size and charge as those found in the controls. There was no evidence of detectable glycosidase activity and only very limited sulphatase activity. A similar rate of breakdown and final distribution pattern was found for newly synthesized proteoglycan. Increased amounts of latent neutral metalloproteinases and acid proteinase activities were present in the medium of depleted cartilage. These were not thought to be involved in the breakdown of proteoglycan. Increased release of proteoglycan ceased within 24h of removal of the catabolin, indicating that the effect was reversible and persisted only while the stimulus was present.

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Enhanced Breakdown of Bovine Articular Cartilage Proteoglycans by Conditioned Synovial Medium in Vitro:The Effect of Glucocorticoids and Protein Synthesis Inhibitors

Cited by 10 publications

References 17 publications

Deficiency of NADPH Oxidase Components p47phox and gp91phox Caused Granulomatous Synovitis and Increased Connective Tissue Destruction in Experimental Arthritis Models

Deficiency of NADPH Oxidase Components p47phox and gp91phox Caused Granulomatous Synovitis and Increased Connective Tissue Destruction in Experimental Arthritis Models

Extracellular superoxide dismutase and oxidant damage in osteoarthritis

Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro

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