Multiple changes in gene expression in chronic human Achilles tendinopathy

TM Ž.Atlas cDNA cell interaction arrays CLONTECH were used to examine degenerate tissue from four patients with Achilles tendon disorders, in order to identify changes in expression of genes important in cellcell and cellmatrix Ž.interactions. The greatest difference between normal post-mortem and degenerate tissue samples was in the level of MMP-3 Ž.stromelysin mRNA, which was down-regulated in all the degenerate samples. Quantitative RT-PCR assay of RNA extracted from paired ‘normal ’ and degenerate Achilles tendon tissue samples taken from tendons during surgery mirrored the results of the arrays. Levels of MMP-3 mRNA were lower, whereas levels of type-I and type-III collagen mRNAs were significantly higher, in the degenerate compared to the ‘normal ’ samples. Immunoblotting of proteins extracted from the same tendon samples showed that three of four normal tissue samples taken from individuals without apparent tendon disorder had much higher levels of MMP-3 protein than ‘normal ’ or degenerate samples from patients with tendinosis. We suggest that MMP-3 may play an important role in the regulation of tendon extracellular matrix degradation and tissue remodelling. 200