Multiple changes in gene expression in chronic human Achilles tendinopathy.
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 cell-cell and cell-matrix interactions. The greatest difference between normal (post-mortem) and degenerate tissue samples was in the level of MMP-3 (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.
Ireland
D
D
Rheumatology Research Unit, Box 194, E6, Addenbrooke's Hospital, Hills Road, CB2 2QQ, Cambridge, UK. dci20@mole.bio.cam.ac.uk
Harrall
R
R
Curry
V
V
Holloway
G
G
Hackney
R
R
Hazleman
B
B
Riley
G
G
D000125:Achilles Tendon / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000302:isolation & purification; D008875:Middle Aged; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA; D019278:Matrix Metalloproteinase 3