Clusterin expression in adult human normal and osteoarthritic articular cartilage

Objective: To characterize the expression pattern of clusterin in adult hum an normal and osteoarthritic cartilage Methods: Clusterin mRNA expression in adult human normal and osteoarthritic cartilage was investigated by analysis of cDNA libraries, TaqMan quantitat ive RT-PCR, microarray and in situ hybridization. Results: Sequence analysis of ESTs from adult human normal and osteoarthrit ic cartilage cDNA libraries demonstrated that the abundance of clusterin in these libraries was equivalent to genes which have been more commonly asso ciated with cartilage. To examine tissue distribution, TaqMan Quantitative PCR analysis was performed using RNA from a panel of individual normal tiss ues. Clusterin was expressed at significant levels in cartilage, brain, liv er, and pancreas. The expression of clusterin mRNA was up-regulated in earl y osteoarthritic vs normal cartilage when analysed by microarray analysis. Using in situ hybridization, chondrocytes of normal cartilage expressed mod erate levels of clusterin. Upper mid-zone chondrocytes in cartilage with ea rly stages of osteoarthritic disease expressed high levels of clusterin mRN A. In advanced osteoarthritic cartilage, the overall expression of clusteri n was reduced. Conclusion: The induction of clusterin has been associated with a variety o f disease states where it appears to provide a cytoprotective effect. The i ncreased expression of clusterin mRNA in the early stages of osteoarthritis (OA) may reflect an attempt by the chondrocytes to protect and repair the tissue. In contrast, the decrease in clusterin mRNA in the advanced osteoar thritic cartilage accompanies the final degenerative stages of the disease. An understanding of the expression of clusterin in osteoarthritis may allo w consideration of this protein as a marker for cartilage changes in this c hronic degenerative condition. (C) 2001 OsteoArthritis Research Society Int ernational.