In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1.

Thomas, D. P. Page; King, Brett; Stephens, Trent D.; Dingle, J. T.

doi:10.1136/ard.50.2.75

Cited by 84 publications

(48 citation statements)

References 6 publications

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“…However, when Dec-RVKR-CH 2 Cl was added on day 7 of culture or even on days 7, 9, and 11, collagen release was not significantly reduced. This demonstrates that the target of Dec-RVKR-CH 2 Cl is present at the beginning of the culture period. In contrast, the addition of ␣ 1 PI on day 0 of culture to cartilage stimulated to resorb did not block collagen release.…”

Section: Resultsmentioning

confidence: 68%

“…The addition of Dec-RVKR-CH 2 Cl to bovine nasal cartilage explant cultures that had been stimulated to resorb with IL-1␣ and OSM produced a dosedependent reduction in the release of collagen fragments ( Figure 1). This inhibition was statistically significant at concentrations Ն65 M. The higher concentration 2 Cl to resorbing bovine nasal cartilage. Bovine nasal cartilage discs were cultured in medium with or without interleukin-1␣/oncostatin M (IL-1␣/OSM) and with or without Dec-RVKR-CH 2 Cl.…”

Section: Resultsmentioning

confidence: 88%

“…In experimental cartilage models, chondrocytes respond to proinflammatory cytokines such as interleukin-1 (IL-1), resulting in the breakdown of the ECM. Degradation of proteoglycan is rapid and reversible (2); however, the breakdown of collagen is slow and is thought to be essentially irreversible (3).…”

mentioning

confidence: 99%

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Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Milner¹,

Rowan²,

Sf³

et al. 2003

Arthritis & Rheumatism

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Objective. To investigate the role of furin-like enzymes in the proteolytic cascades leading to cartilage breakdown and to examine which collagenase(s) contribute to collagen degradation.Methods. Bovine nasal cartilage was stimulated to resorb with the addition of interleukin-1␣ (IL-1␣)/ oncostatin M (OSM) in the presence or absence of a furin inhibitor, Dec-RVKR-CH 2 Cl, or selective matrix metalloproteinase 1 (MMP-1) inhibitors. Collagen and proteoglycan levels were determined by assay of hydroxyproline and sulfated glycosaminoglycan, respectively. Collagenase and gelatinase activity were measured using 3 H-acetylated collagen and gelatin zymography, respectively.Results. The addition of Dec-RVKR-CH 2 Cl to stimulated cartilage reduced the release of collagen fragments and the levels of active collagenase and MMP-2, suggesting that furin-like enzymes are involved in the cascades leading to activation of procollagenases. At MMP inhibitor concentrations that selectively inhibit MMP-1, no inhibition of collagen release was observed, but increasing the concentration to the 50% inhibition concentration for MMP-13 resulted in a 50% blockage of collagen release. The addition of Dec-RVKR-CH 2 Cl to resorbing cartilage also partially blocked proteoglycan release, thus demonstrating a role for furin-activated enzymes in the pathways leading to proteoglycan degradation. Conclusion.Furin-like enzymes are involved in cascades leading to activation of procollagenases and degradation of collagen. MMP-13, which can be activated by furin-processed membrane-type 1 MMP-1, appears to be a major collagenase involved in collagen degradation induced by IL-1␣/OSM. Furin-like enzymes also appear to play a role in the pathways leading to proteoglycan degradation. These findings are of importance when considering proteinase inhibition as a target for therapeutic intervention in arthritic diseases.

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Section: Resultsmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 88%

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Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Milner¹,

Rowan²,

Sf³

et al. 2003

Arthritis & Rheumatism

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“…The role of IL-1, together with TNF-, in matrix degradation has been clarified [471]. Of note, when IL-1 is combined with TNF-and the two are injected simultaneously, there is enhanced cartilage destruction, which exceeds the effects observed with either cytokine alone [472]. The combination of IL-1 and oncostatin M also upregulates matrix-degrading proteinases in cartilage [473].…”

Section: Metalloproteinases and Osteoarthritismentioning

confidence: 99%

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Gargiulo¹,

Gamba²,

Poli³

et al. 2014

CPD

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Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS).This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

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“…Cartilage degradation is mediated predominantly by the matrix metalloproteinases (MMPs), a family of potent enzymes that, collectively, can degrade all ECM components and that have been strongly implicated in arthritic joints (1). Aggrecanolysis is considered to be mediated by the ADAMTS proteinases (2), although this ECM component can be replaced relatively rapidly once the stimulus, such as interleukin-1 (IL-1), has been removed (3). In contrast, collagen is much less readily released, but when degradation does occur, tissue integrity is irreversibly lost (4).…”

mentioning

confidence: 99%

Interleukin‐1 in combination with oncostatin M up‐regulates multiple genes in chondrocytes: Implications for cartilage destruction and repair

Barksby¹,

Wang²,

Wappler³

et al. 2006

Arthritis & Rheumatism

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In vivo studies of cartilage regeneration after damage induced by catabolin/interleukin-1.

Abstract: The response of the rabbit knee joint to a brief episode of cytokine induced damage is described. After three intra-articular injections of catabolin/interleukin-I all joint cartilages showed an immediate extensive loss of proteoglycan (glycosaminoglycan)

Cited by 84 publications

References 6 publications

Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Inhibition of furin‐like enzymes blocks interleukin‐1α/oncostatin M–stimulated cartilage degradation

Metalloproteinases and Metalloproteinase Inhibitors in Age-Related Diseases

Interleukin‐1 in combination with oncostatin M up‐regulates multiple genes in chondrocytes: Implications for cartilage destruction and repair

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