Multiple changes in gene expression in chronic human Achilles tendinopathy

Atlas(TM) cDNA cell interaction arrays (CLONTECH) were used to examine dege nerate tissue from four patients with Achilles tendon disorders, in order t o identify changes in expression of genes important in cell-cell and cell-m atrix interactions. The greatest difference between normal (post-mortem) an d degenerate tissue samples was in the level of MMP-3 (stromelysin) mRNA, w hich was down-regulated in all the degenerate samples. Quantitative RT-PCR assay of RNA extracted from paired 'normal' and degenerate Achilies tendon tissue samples taken from tendons during surgery mirrored the results of th e arrays. Levels of MMP-3 mRNA were lower, whereas levels of type-I and typ e-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 ten don extracellular matrix degradation and tissue remodelling. (C) 2001 Elsev ier Science B.V./International Society of Matrix Biology. All rights reserv ed.