IMMUNOLOCALIZATION OF STROMELYSIN, TUMOR-NECROSIS-FACTOR (TNF)-ALPHA,AND TNF RECEPTORS IN ATROPHIED CANINE ARTICULAR-CARTILAGE TREATED WITH HYALURONIC-ACID AND TRANSFORMING GROWTH-FACTOR-BETA

Objective-To evaluate the ability of hyaluronic acid (HA), with and wi thout transforming growth factor beta (TGF-beta), to stabilize the cat abolic processes associated with atrophy of articular cartilage. Anima ls-20 adult, skeletally normal, hound-type dogs. Procedure-Dogs (20 to 30 kg) were randomly assigned to 1 oi 5 groups, One group served as u ntreated controls. Bivalve casts were placed on the left hind limbs of the remaining 16 dogs to limit weightbearing and motion of the limb f or 92 days. One group served as the cast control. Beginning on day 56, 3 groups received aseptic intra-articular injections in the left stif les of either 5 mg of HA or 5 mg of HA containing either 20 or 50 mu g of TGF-beta. Intra-articular injections were repeated al 4-day interv als until the end oi the study. On day 92, stifles were harvested at n ecropsy. Medial femoral condyles were histologically processed, and th e articular cartilage was stained for the presence of proteoglycans, s tromelysin, tumor necrosis factor (TNF) alpha, and TNF receptors (p55 and p75). Results-Decreased metachromasia was evident in the cartilage matrix of al cast groups, with the smallest decrease in the HA-treate d group. Stromelysin was immunolocalized in articular cartilage of til e cast (left) limbs of cast control and both HA/TGF-beta-treated group s. TNF-alpha was localized in articular cartilage of all cast (left) a nd right limbs, except those of the HA-treated group. Receptors for TN F were observed in both limbs of untreated control and cast control gr oups and cast limbs of HA/TGF-beta-treated groups, The receptors were not localized in the right limbs of the HA with or without TGF-beta-tr eated groups. TGF-beta did not decrease stromelysin or TNF-alpha or re ceptors at the doses used. Conclusions-HA may mediate a chondrostabili zing influence on articular cartilage by down-regulating TNF-alpha. Im portantly, HA appeared to exert its inhibitory influence on TNF-alpha, as well as stromelysin and TNF receptors, on a systemic basis. Clinic al Relevance-Results provide insight into the mode of action of HA as a therapeutic agent for arthritis and its stabilizing influence on car tilage metabolism.