Use of synovial fluid markers of cartilage synthesis and turnover to study effects of repeated intra-articular administration of methylprednisolone acetate on articular cartilage in vivo.

The study investigates the impact of intra-articular corticosteroids on articular cartilage using synovial fluid markers. The findings suggest a potentially harmful effect from repeated use, resulting in inhibited synthesis of procollagen II and increased release of degradation products from articular cartilage.

Study Design and Methodology

• The research involved studying paired radiocarpal joints from 10 adult horses that showed no clinical or radiographic signs of joint disease.
• The procedure called aseptic arthrocentesis was carried out weekly for 13 weeks. This procedure involves puncturing the joint cavity in order to obtain a synovial fluid (SF) sample.
• Intra-articular injections of methylprednisolone acetate (MPA) were administered into the treatment joint, with the control joint receiving a vehicle injection, at weeks 3, 5, and 7 of the study period.

Assessment and Analysis of Synovial Fluid

• Radioimmunoassays, a technique involving the use of radioactive isotopes to measure antigen concentrations, were used on the SF samples to detect the 846 epitope on cartilage aggrecan, a keratan sulfate epitope (KS), and the C-propeptide (CPII) of cartilage type II procollagen, which is released following the synthesis of this molecule.
• Through gel chromatography on selected SF samples, the research team evaluated the sizes of SF PG molecules. This helped them understand the distribution of these molecules and assess their breakdown.
• The KS and 846 epitopes, which were present on most molecules, appeared to be primarily fragments of articular cartilage aggrecan based on chromatographic analysis.

Results and Implications

• The study found a significant increase in KS and 846 epitopes in MPA joints compared to control joints during the treatment period.
• In contrast, CPII was significantly reduced in the MPA joints, indicating a decrease in the synthesis of type II procollagen, a crucial component of cartilage.
• The results suggest that repeated use of intra-articular MPA could lead to a harmful inhibition of procollagen II synthesis and an increased release of degradation products of the aggrecan from articular cartilage.
• This reveals potentially detrimental effects of such treatment on joint health, thereby raising questions about the wisdom of using intra-articular corticosteroids repeatedly.