Microarray analysis reveals the involvement of beta-2 microglobulin (B2M) in human osteoarthritis

OBJECTIVE: To assess whether beta-2 microglobulin (B2M) has effects on articular chondrocytes that would implicate B2M involvement in osteoarthritis (OA) pathogenesis. METHODS: The mRNA levels of B2M in fetal and osteoarthritic chondrocytes were detected by RT-PCR. B2M levels in synovial fluid and tissue cultured media from cartilage explants were tested using B2M ELISA kit. Primary cultured chondrocytes were used for proliferation and microarray experiments. RESULTS: The average B2M level in OA synovial fluid is significantly higher than that found in normal synovial fluid. However, there was no significant difference in B2M synovial fluid levels amongst differing OA stages. The release of B2M by osteoarthritic cartilage was detectable after 24h in culture and continued to increase during the 72 h study period. B2M had an inhibitory effect on chondrocyte growth at 1.0 microg/ml, and became significantly inhibitory at 10.0 microg/ml. Genes regulated by B2M were detected through microarray technology. Twenty genes were found to be up-regulated by B2M, including collagen type III which is known to be up-regulated in OA. Eleven genes were found to be down-regulated at least two-fold by B2M. CONCLUSION: These results indicate that B2M is highly expressed in OA cartilage and synovial fluid compared to normal, and suggest that B2M may have effects on chondrocyte function that could contribute to OA pathogenesis.Copyright 2002 OsteoArthritis Research Society International. Published by Elsevier Science Ltd.