The rates of incorporation of radiolabelled leucine into aggrecan and link protein have been measured in human articular cartilage of different ages. Aggrecan and link protein were purified in the A1 fraction of CsCl gradients as a result of their ability to form high-buoyant-density proteoglycan aggregates with hyaluronic acid. Separation of the aggrecan from the link protein was achieved by Mono Q anion-exchange chromatography. The rates of synthesis of both aggrecan and link protein decreased with age. The age-related decrease in synthesis of aggrecan was paralleled by a decrease in the rate of sulphate incorporation into glycosaminoglycan chains. The synthesis of link protein decreased with age to a greater extent than that of aggrecan such that the ratio of the rates of link protein to aggrecan synthesis decreased from 1 in immature cartilage to 0.2 in mature cartilage. The age-related decrease in link protein synthesis is controlled at least in part by transcriptional or post-trancriptional mechanisms, as shown by the accompanying age-related decrease in link-protein mRNA. The absence of any age-related decrease in aggrecan mRNA suggests that the decrease in synthesis of aggrecan core protein is controlled by a translational mechanism. Measurement of the total tissue content of aggrecan and link protein by radioimmunoassay revealed an age-related increase in the accumulation of these matrix proteins, even though their de novo synthesis was decreasing. This illustrates the importance that the regulation of extracellular post-translational modification also has in controlling the overall turnover of the cartilage matrix.
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January 1999
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Research Article|
December 17 1998
Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability
Mark C. BOLTON;
Mark C. BOLTON
*The Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London W6 8LH, U.K.
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Jayesh DUDHIA;
Jayesh DUDHIA
†Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
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Michael T. BAYLISS
Michael T. BAYLISS
1
†Department of Veterinary Basic Sciences, The Royal Veterinary College, Royal College Street, London NW1 0TU, U.K.
1To whom correspondence should be addressed (email mbayliss@rvc.ac.uk).
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Publisher: Portland Press Ltd
Received:
May 22 1998
Revision Received:
September 30 1998
Accepted:
October 14 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1999
1999
Biochem J (1999) 337 (1): 77–82.
Article history
Received:
May 22 1998
Revision Received:
September 30 1998
Accepted:
October 14 1998
Citation
Mark C. BOLTON, Jayesh DUDHIA, Michael T. BAYLISS; Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability. Biochem J 1 January 1999; 337 (1): 77–82. doi: https://doi.org/10.1042/bj3370077
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