The effect of serum on biosynthesis of proteoglycans by bovine articular cartilage in culture

Hascall, Vincent C.; Handley, Christopher J.; McQuillan, David J.; Hascall, Gretchen K.; Robinson, H C; Lowther, Dennis A.

doi:10.1016/0003-9861(83)90205-9

Cited by 179 publications

(114 citation statements)

References 43 publications

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“…The higher baseline of type I1 collagen expression in monolayer chondrocyte cultures may magnify methylprednisolone-induced suppression. Maintaining a rounded morphology [5,7,24] and integrity of the cartilage extracellular matrix [9,22,44,49] supports stability of the chondrocytic phenotype in culture and may lessen the effects of corticosteroid exposure. Finally, although the articular cartilage was selected only from weight-bearing locations, neither the explant nor isolated chondrocyte culture systems can address the cellular heterogeneity of articular cartilage.…”

Section: Discussionmentioning

confidence: 99%

Corticosteroids alter the differentiated phenotype of articular chondrocytes

Fubini

Todhunter

Burton‐Wurster

et al. 2001

Journal Orthopaedic Research

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Experimental evidence suggests that recommended dosages of some corticosteroids used clinically as antiinflammatory agents for treating arthropathies damage articular cartilage, but low dosages may be chondroprotective. The purpose of this study was to evaluate how different concentrations of methylprednisolone affect chondrocyte function and viability. Articular cartilage and chondrocytes were obtained from young adult horses, 1 5 3 . 5 years of age. Corticosteroid-induced changes in collagen expression were studied at the transcriptional level by Northern blot analyses and at the translational level by measuring [3H]-proline incorporation into [3H]-hydroxyproline. Fibronectin mRNA splicing patterns were evaluated with ribonuclease protection assays. Cytotoxicity was studied using erythrosin B dye exclusion. Steady-state levels of type I1 procollagen mRNA decreased without concurrent changes in type I procollagen expression as the medium methylprednisolone concentrations were increased from 1 x lo1 to 1 x 10' pg/ml, dropping below 10% of control values by 1 Y lo5 pg/ml. Cytotoxicity occurred as methylprednisolone levels were increased further from 1 x loR to 1 A lo9 pg/ml. Changes in total collagen (protein) synthesis were less pronounced, but also demonstrated significant suppression between 1 x lo4 and 1 x lo8 pg/ml. Corticosteroid-induced changes in fibronectin isoform levels were evaluated in articular cartilage samples without in vitro culture. The cartilage-specific (V + C)-isoform was suppressed in both normal and inflamed joints by a single intraarticular injection (0.1 mg/kg) of methylprednisolone. Combined, these data indicate that methylprednisolone suppresses matrix protein markers of chondrocytic differentiation. Decreased and altered chondrocyte expression of matrix proteins likely contributes to the pathogenesis of corticosteroid-induced cartilage degeneration.

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Section: Discussionmentioning

confidence: 99%

Corticosteroids alter the differentiated phenotype of articular chondrocytes

Fubini

Todhunter

Burton‐Wurster

et al. 2001

Journal Orthopaedic Research

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“…Because we were using a model representative of cartilage breakdown, we avoided using serum (6,7,15), which contains chondroprotective agents, such as insulin-like growth factor 1 (17), that can block cartilage collagenolysis (18). The absence of serum does not affect cell viability (data not shown), and previous studies have shown that cartilage in serum-free culture for up to 8-9 days can respond to serum and other growth factors (19).…”

Section: Methodsmentioning

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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“…The aim of this study was to create a model of cartilage breakdown; therefore, the presence of serum was avoided because it contains chondroprotective agents such as insulin-like growth factor 1 (42,43). The absence of serum was shown not to affect the viability of the tissue, and previous studies have shown that cartilage in serum-free culture for 8 or 9 days can respond to serum and other growth factors (44). In the present study, cytokines were added after 1 day of serum-free culture.…”

Section: Methodsmentioning

confidence: 99%

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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The effect of serum on biosynthesis of proteoglycans by bovine articular cartilage in culture

Cited by 179 publications

References 43 publications

Corticosteroids alter the differentiated phenotype of articular chondrocytes

Corticosteroids alter the differentiated phenotype of articular chondrocytes

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

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

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