Topographic variation in biglycan and decorin synthesis by articular cartilage in the early stages of osteoarthritis: an experimental study in sheep.
Articular cartilage contains large molecular weight proteoglycans that aggregate with hyaluronic acid (aggrecan) and small species, particularly biglycan (dermatan sulphate proteoglycan-1) and decorin (dermatan sulphate proteoglycan-2), that do not. Mechanical stresses have been shown to profoundly influence the metabolism of aggrecan by articular chondrocytes; however, there are limited corresponding data on the metabolism of dermatan sulphate proteoglycans 1 and 2. The objective of this study was to examine the metabolism of aggrecan, biglycan, and decorin in articular cartilage from different weight-bearing areas of normal ovine stifle joints and in joints 6 months after menisectomy, a procedure that has been shown to induce early osteorthritic changes. [35S]proteoglycans synthesised by cartilage explants from eight different weight-bearing regions of unoperated and meniscectomised ovine stifle joints during 48 hours of culture were separated by size-exclusion chromatography, hydrophobic chromatography, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were quantitated by phosphor-screen autoradiography. The synthesis and degradation of the proteoglycans were expressed relative to the DNA content of the explants. In control joints, the cartilage exposed to high contact stress synthesised significantly less proteoglycan overall and more decorin than joint regions bearing less stress. Explants from high stress regions also released significantly greater amounts of resident proteoglycans (dimethylmethylene blue positive) into media during culture. After lateral meniscectomy, the lateral tibial and femoral cartilages showed elevated biosynthesis of both 35S-dermatan sulphate proteoglycans 1 and 2. This chondrocyte biosynthetic response was accompanied by increased catabolism of aggrecan and the release of its degradation products into culture media. These experiments revealed, in normal joints, a topographic variation in proteoglycan synthesis by articular cartilage that was related to the mechanical stress to which the tissues were subjected in vivo. This biosynthetic pattern changed when the load distribution of the joint was altered by unilateral meniscectomy. These data suggest that an altered chondrocyte phenotypic expression of proteoglycans in response to abnormal mechanical loading is an early event in osteoarthritis.
Little
C B
CB
Raymond Purves Bone and Joint Research Laboratories, Royal North Shore Hospital, St. Leonards, New South Wales, Australia.
Ghosh
P
P
Bellenger
C R
CR
D053674:Aggrecans; D000818:Animals; D058578:Biglycan; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D011508:Chondroitin Sulfate Proteoglycans / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D058575:Decorin; D003871:Dermatan Sulfate / Q000032:analysis / Q000096:biosynthesis / Q000378:metabolism; D004195:Disease Models, Animal; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008297:Male; D008592:Menisci, Tibial / Q000737:chemistry / Q000601:surgery; D010003:Osteoarthritis / Q000378:metabolism*; D011509:Proteoglycans / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D012756:Sheep
D053674:Aggrecans; D058578:Biglycan; D011508:Chondroitin Sulfate Proteoglycans; D003470:Culture Media; D058575:Decorin; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D003871:Dermatan Sulfate