[An experimental study on the pathogenesis of osteoarthritis--histological and biochemical changes of proteoglycan in the osteoarthritic cartilage of rabbit in the early stage-- (author's transl)].

Osteoarthritis is generally a slowly progressive destructive disease of joints. As the disease is asymptomatic in its initial phases, it was detectable only at the later stage when radiological changes and clinical symptom had developed. The biochemical and cellular changes that had been recorded were those of the later clinically recognizable stage of the disease. Because the time of onset in not known, the initial events which might be the most important to investigate the pathogenesis of osteoarthritis, are virtually impossible to investigate except in experimentally induced models of osteoarthritis. For the purpose of investigating the pathogenesis of degenerative osteoarthritis, experimental osteoarthritic model was prepared. Section of the medial collateral and both cruciate ligaments combined with resection of the medial meniscus in adult rabbit knees showed progressive histological changes similar to those in human osteoarthritis. Therefore, qualitative and progressive alteration of the cartilage matrix proteoglycan in experimental osteoarthritis of the early stages were investigated with time. Biochemical analysis of the cartilage from experimental osteoarthritic model demonstrated a decrease in the content of glycosaminoglycan and increase in the rate of the synthesis of glycosaminoglycan as compared to the normals. The analysis of disaccharide chain revealed a decrease in the concentration of kelatan sulfate and chondroitin-6 sulfate, along with an increase in the concentration of chondroitin-4 sulfate. These findings, which were quite consistent with those in human osteoarthritis and were contrary to those in aging, indicate the attempts of cells to compensate for the proteoglycan deficiency in osteoarthritic cartilage by synthesizing large quantities of glycosaminoglycans of immature pattern. On the other hand, synthesized aggregated proteoglycans in arthritic cartilage had shown a polydispersive pattern in CsCl density gradient compared to that of normal one, which had shown a single curved pattern. Further, newly synthesized proteoglycan in osteoarthritic cartilage seemed to be polydispersive compared with control proteoglycan in molecular sizes on Sepharose 2B gel chromatography under non-aggregated dissociative condition. Large molecular size proteoglycan composed of small molecular size glycosaminoglycan on its polysaccharide chain and small molecular size proteoglycan composed of large molecular size glycosaminoglycan. This might represent the expression of repair mechanism in the damaged cartilage, or phenotypic transformation of extracellular macromolecule in osteoarthritis.