Differential expression of Egr-1 in osteoarthritic compared to normal adult human articular cartilage

Objective: The purpose of this study was to identity genes that are differe ntially expressed in normal versus osteoarthritic human articular cartilage as either potential novel therapeutic targets or diagnostic markers of thi s disease. Design: mRNA was isolated from histologically normal and osteoarthritic adu lt human articular cartilage. The Differential Display technique was employ ed which identified differentially expressed genes in the normal and diseas ed tissue. Northern and reverse Northern hybridization were used to confirm the gene expression pattern. Immunohistochemistry and in-situ hybridizatio n were used to localize expression of Egr-1 protein and mRNA respectively i n cartilage. Results: A transcription factor, early growth response protein-1 (Egr-1) wa s found to be down-regulated more than six-fold in multiple human OA cartil age samples when compared to normal tissue. Immunohistochemistry indicated that Egr-1 was expressed throughout normal adult cartilage, in deep-, mid- and superficial-zones. In contrast, in OA cartilage there was expression of Egr-1 mRNA and protein only in the chondrocytes undergoing cloning. Conclusions: Egr-1 is differentially expressed in OA versus normal cartilag e and because of its role in transcriptional activation and repression and regulation of proliferation, differentiation and apoptosis, Egr-1 may play an important role in the pathogenesis of OA. Up-regulation of Egr-1 may the refore provide a novel therapeutic approach for either the prevention or tr eatment of OA. (C) 2000 OsteoArthritis Research Society International.