Document Detail

Modulation of intracellular reactive oxygen species level in chondrocytes by IGF-1, FGF, and TGF-beta1.
MedLine Citation:
PMID:  17522998     Owner:  NLM     Status:  MEDLINE    
Growth factors are important in the development, maintenance and repair of cartilage. The principal aim of this study was to test the capacity of three growth factors with established roles in cartilage, namely insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF) and transforming growth factor (TGF)-beta 1, to alter intracellular reactive oxygen species (ROS) levels. Explants of articular cartilage from young, mature, and aged rats were pretreated with IGF-1, FGF, or TGF-beta 1 and intracellular ROS levels were quantified using the free radical sensing probe dihydrorhodamine 123 (DHR 123), confocal microscopy, and densitometric image analysis. Viability of chondrocytes following ROS stress and growth factor treatment was assessed using the live/dead cytotoxicity assay, and the activities of the antioxidant enzymes--catalase (CAT), total superoxide dismutase (SOD), and glutathione peroxidase (GPX)--were measured spectrophotometrically by decay of the substrate from the reaction mixture. The effect of IGF-1 on ROS levels in cultured human chondrocytes also was examined. In rat cartilage, FGF did not significantly affect ROS levels or antioxidant enzyme activity in any age group. TGF-beta1 significantly increased cellular ROS levels in mature and old cartilage whereas in marked contrast, IGF-1 significantly and age-dependently reduced ROS levels. IGF-1 also had a potent antioxidant effect on cultured human chondrocytes. Pretreatment of rat cartilage with IGF-1 significantly enhanced the activity of GPX, without altering the activity of SOD or CAT, and protected chondrocytes against ROS-induced cell death. TGF-beta 1 had no significant effect on the activity of the antioxidant enzymes. Despite promoting ROS production, TGF-beta 1 was not cytotoxic. We concluded that TGF-beta 1 exhibits an acute pro-oxidant effect in cartilage that is not cytotoxic, suggesting a role in physiological cell signalling. In marked contrast, IGF-1 is a potent antioxidant in mature and aged rat and human chondrocytes, protecting cells against ROS-induced cell death probably through the enhancement of the activity of the antioxidant enzyme GPX.
Navid Jallali; Hyder Ridha; Christopher Thrasivoulou; Peter Butler; Timothy Cowen
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Connective tissue research     Volume:  48     ISSN:  0300-8207     ISO Abbreviation:  Connect. Tissue Res.     Publication Date:  2007  
Date Detail:
Created Date:  2007-05-24     Completed Date:  2007-10-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0365263     Medline TA:  Connect Tissue Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  149-58     Citation Subset:  IM    
Department of Anatomy and Developmental Biology, University College London, London, United Kingdom.
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MeSH Terms
Antioxidants / metabolism
Catalase / metabolism
Cell Communication / drug effects
Cell Survival / drug effects
Cells, Cultured
Chondrocytes / drug effects*,  metabolism*
Fibroblast Growth Factor 2 / pharmacology*
Glutathione Peroxidase / metabolism
Insulin-Like Growth Factor I / pharmacology*
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism*
Superoxide Dismutase / metabolism
Transforming Growth Factor beta1 / pharmacology*
Reg. No./Substance:
0/Antioxidants; 0/Reactive Oxygen Species; 0/Transforming Growth Factor beta1; 103107-01-3/Fibroblast Growth Factor 2; 67763-96-6/Insulin-Like Growth Factor I; EC; EC Peroxidase; EC Dismutase

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