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Sodium hyaluronate (HA) with a molecular weight of approximately 600,000-1,200,000 is reportedly effective against osteoarthritis (OA). However, since HA with higher molecular weight is expected to be more effective against OA, we investigated the effects of HA (SL-1010) newly produced by fermentation with a molecular weight of 1,800,000-2,100,000 on the experimental OA induced by intraarticular injection of papain, into the knee joint of the rabbit, in comparison with those of HA with a molecular weight of about 950,000 (HA-95). When 0.4, 0.8, and 1.6% papain (0.5ml) was injected into the knee joint of the animal twice with a 3-day interval, there were dose-dependent degenerative changes and a decrease in sulfated glycosaminoglycan (S-GAG) in the articular cartilage with slight synovial inflammatory changes 6 weeks after the final injection of papain. In this OA model, intraarticular application of SL-1010 slightly reduced the degeneration of articular cartilage, compared with the injections of HA-95 or saline (control). SL-1010 also caused a significant recovery in the S-GAG level which was decreased in the cartilage of the OA model, compared with the control. In addition, SL-1010 inhibited the release of 35S-GAG from the cartilage obtained from normal and OA model joints. These results suggest that SL-1010 is effective in inhibiting the degeneration of cartilage in the OA model, probably due to the recovery of the S-GAG level by reducing the release of S-GAG from the cartilage.

Effects of SL-1010 on the experimental osteoarthritis (OA) produced by intra-articular injection of papain, proteolytic enzyme, in the knee joint of the guinea pigs were histologically and biochemically investigated. In addition, experimental conditions to produce OA in guinea pig knee joint were also examined, since papain-induced OA has been mainly studied in rabbits. Six weeks after intra-articular injection of papain (1%, 0.1 ml), there were inflammatory reactions of the synovial membrane, degenerative changes in chondrocytes and the matrix of the articular cartilage, a decrease in the Safranin-O staining intensity and lowering of sulfated glycosaminoglycan. Electronmicroscopic observations revealed that the amorphous layer had disappeared and large bundles of unit collagen fibers and larger collagen fibers had appeared in the cartilage matrix. In the OA model, SL-1010 reduced the inflammatory reactions of the synovial membrane, inhibited development of degenerative changes in chondrocytes and the matrix of the articular cartilage and recovered the Safranin-O staining intensity. The sulfated glycosaminoglycan contents in the cartilage was significantly increased in the SL-1010-treated group, compared with the control group. The electromicroscopically observed charges in the papain-injected knee joint of the control group were rarely detected in the SL-1010-treated group. These results suggest that SL-1010 inhibits degenerative changes in the chondrocytes and the matrix probably by reducing synovial inflammation and protection of the cartilage in the OA model of guinea pigs.

The effect of Neurotropin on osteoarthritis was investigated in comparison with those of prednisolone and indomethacin. 1) There were remarkable decreases in the staining intensity to safranin-O and in the contents of uronic acid, total hexosamine and hexose in the articular cartilage of rabbits in which experimental osteoarthritis was induced by the injection of papain into the knee joint. In the Neurotropin-treated group, the decrease in the staining intensity to safranin-O and the contents of uronic acid, total hexosamine and hexose were evidently recovered. On the other hand, in the prednisolone- or indomethacin-treated group, the degeneration of the cartilage was even more pronounced than in the control group treated with papain alone. 2) Neurotropin had no effect on the autolytic degradation of cartilage, but promoted the incorporation of 14C-acetate into the proteoglycan in the articular cartilage of rabbits. 3) Both prednisolone and indomethacin inhibited the autolytic degradation and the incorporation of 14C-acetate into the proteoglycan. These results suggested that the therapeutic effect of Neurotropin on osteoarthritis may be due to the improvement of decreased proteoglycan content in the matrix of articular cartilage; and in this respect, it is different from anti-inflammatory drugs such as prednisolone and indomethacin.