title: Age-related changes in the synthesis of link protein and aggrecan in human articular cartilage: implications for aggregate stability.
abstract: 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-transcriptional 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.
authors.affiliation: The Kennedy Institute of Rheumatology, 1 Aspenlea Road, Hammersmith, London W6 8LH, U.K.
authors.forename: M C
authors.initials: MC
authors.lastname: Bolton
authors.forename: J
authors.initials: J
authors.lastname: Dudhia
authors.forename: M T
authors.initials: MT
authors.lastname: Bayliss
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D053674:Aggrecans; D000375:Aging / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism*; D002648:Child; D016326:Extracellular Matrix Proteins; D006801:Humans; D007700:Kinetics; D037181:Lectins, C-Type; D007930:Leucine / Q000378:metabolism; D008875:Middle Aged; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011509:Proteoglycans / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D000099249:Proteoglycan Link Protein
chemical_list: D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D007930:Leucine; D011506:Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D000099249:Proteoglycan Link Protein