ACUTE SYNOVITIS AND INTRAARTICULAR METHYLPREDNISOLONE ACETATE IN PONIES

Objective: To determine how acute synovitis, with and without intra-ar ticular methylprednisolone acetate (MPA), affect synthesis of proteogl ycan, total protein, and collagen in articular cartilage and total pro tein synthesis in synovial membrane. Design: Synovitis was induced in 10 ponies by the injection of 0.5 ng lipopolysaccharide (LPS) into the left radiocarpal and midcarpal joints every 2 days for a total of fou r treatments. Synovitis was documented by clinical examination and syn ovial fluid analyses. Two days before euthanasia, MPA (0.1 mg/kg) was injected with the last dose of LPS into both the left and right radioc arpal and midcarpal joints of five of these ponies. Proteoglycan synth esis in articular cartilage explants from these joints was measured by incorporation of sodium [S-35]sulfate. The size of the proteoglycan m onomers and their aggregation with hyaluronan was assessed by size-exc lusion chromatography. Protein synthesis in articular cartilage was me asured by incorporation of [H-3]proline and collagen synthesis by conv ersion of [H-3]proline into [H-3]hydroxyproline. Protein synthesis was measured in synovial membrane explants by incorporation of [S-35]meth ionine. Results: Ponies developed carpal effusion and mild lameness ac companied by increased total nucleated cell count and total solids in synovial fluid in response to the LPS injections. Moderate to severe s ynovial membrane proliferation and inflammation were observed histopat hologically in joints injected with LPS but no consistent light-micros copical changes were observed in the articular cartilage from these jo ints. Intra-articular MPA alone was associated with decreased proteogl ycan synthesis and increased protein and collagen synthesis in the car tilage explants. Total protein synthesis by synovial membrane was also increased by MPA alone. In contrast, no differences in protein or pro teoglycan synthesis were observed in explants from the joints with syn ovitis, with or without intra-articular MPA. Treatment with MPA, LPS, and LPS/MPA did not alter proteoglycan aggregate size, but LPS-induced synovitis resulted in an increase in the second largest population of monomers. MPA increased the synthesis of small proteoglycan monomers. Conclusion: Based on the methods used, acute synovitis prevented chan ges induced by intra-articular MPA alone. Results suggested that the e ffect of intra-articular MPA on joint metabolism was different between inflamed and normal joints. Experimental studies must consider the ef fect of inflammation, as well as the potential to introduce in vitro c ulture artifacts when investigating the effect of intra-articular cort icosteroids on chondrocyte function.