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, particul arly 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 oo on the metabolism of dermatan sulphate proteoglycans 1 and 2. The objective o f 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 meniscectomy, a procedure that has been shown to induce early osteoarthritic changes . [S-35]proteoglycans synthesised by cartilage explants from eight dif ferent weight-bearing regions of unoperated and meniscectomised ovine stifle joints during 48 hours of culture were separated by size-exclus ion chromatography, hydrophobic chromatography, and sodium dodecyl sul fate-polyacrylamide gel electrophoresis and were quantitated by phosph or-screen autoradiography. The synthesis and degradation of the proteo glycans were expressed relative to the DNA content of the explants. In control joints, the cartilage exposed to high contact stress synthesi sed significantly less proteoglycan overall and more decorin than join t regions bearing less stress. Explants from high stress regions also released significantly greater amounts of resident proteoglycans (dime thylmethylene blue positive) into media during culture. After lateral meniscectomy, the lateral tibial and femoral cartilages showed elevate d biosynthesis of both S-35-dermatan sulphate proteoglycans 1 and 2. T his chondrocyte biosynthetic response was accompanied by increased cat abolism of aggrecan and the release of its degradation products into c ulture media. These experiments revealed, in normal joints, a topograp hic variation in proteoglycan synthesis by articular cartilage that wa s 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 sugge st that an altered chondrocyte phenotypic expression of proteoglycans in response to abnormal mechanical loading is an early event in osteoa rthritis.