MOLECULAR WEIGHT-DEPENDENT EFFECTS OF HYALURONATE ON THE ARTHRITIC SYNOVIUM

Intra-articular injection of hyaluronate (HA) is widely used in the tr eatment of arthropathies. However, the mechanism of the effects of HA preparations on the arthritic synovium and the relationship between th eir effects and molecular weights (MW) remains unknown. The objectives of this study mere to compare the effects of two hyaluronate preparat ions, HA84 (MW: 84X10(4)) and HA230 (MW: 230X10(4)), on the synovium o f an arthritis model and to examine the mechanism of the effects of HA . The HA preparations were intra-articularly injected in a model of ca nine arthritis induced by anterior cruciate ligament transection for a total trial of 5 weeks. To define the accessibility of HA preparation s to the synovial lining layers, fluorescein-labeled HA84 or HA230 was injected at the last administration. Pathological changes analyzed in cluded increases in volumes and prostaglandin E-2 concentrations in sy novial fluids, thickening of the synovial lining layers, vacuolar alte rations in the lining cells, and stainability of HA in the synovium. E xpression levels of Heat shock protein 72 (Hsp72) were immunohistochem ically detected in the tissues to investigate the ability of the cells to survive the degeneration. The pathological changes described above mere more significantly suppressed in the HA230-treated than in the H A230-treated groups. In most cases of the HA84-treated group (five cas es out of six), fluorescein particles were intensely distributed in th e synovial lining layers, but only two cases in the HA230-treated grou p showed a weak distribution of fluorescein particles in the layers, i ndicating a certain difference in the accessibility of HA preparations to the lining cells between the two HA molecules. Moreover, the immun oreactivity for Hsp72 in the lining cells as more intense in the HA84- treated than in the HA230-treated groups. The difference in the access ibility of HA molecules corresponded well with that in the inducibilit y of Hsp72 in the lining cells. These results suggest that the up-regu lation of Hsp72 may offer a new concept concerning mechanism of the ef fects of HA preparations on the arthritic synovium.