Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy

• Published in: Arthritis and rheumatism 2010-10, Vol.62 (10), p.3028-3035
• Main Authors: Parkinson, John, Samiric, Tom, Ilic, Mirna Z., Cook, Jill, Feller, Julian A., Handley, Christopher J.
• Format: Article
• Language: English
• Subjects: Aggrecans - metabolism; Biological and medical sciences; Case-Control Studies; Diseases of the osteoarticular system; Gene Expression Profiling; Humans; Juxtaarticular diseases. Extraarticular rhumatism; Matrix Metalloproteinase 9 - genetics; Matrix Metalloproteinase 9 - metabolism; Medical sciences; Miscellaneous. Osteoarticular involvement in other diseases; Patellar Ligament - enzymology; RNA, Messenger - metabolism; Tendinopathy - metabolism; Tissue Culture Techniques; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Versicans - metabolism
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.27587

Objective To determine differences in the metabolism of proteoglycans and the gene expression of proteinases and their inhibitors between patellar tendons exhibiting chronic overuse tendinopathy and normal patellar tendons in humans. Methods Rates of loss and synthesis of proteoglycans were determined. Radiolabeled and total proteoglycans retained in and lost from the tissue were analyzed by fluorography and Western blotting. Levels of messenger RNA for matrix metalloproteinase 1 (MMP‐1), MMP‐2, MMP‐3, MMP‐9, MMP‐13, ADAMTS‐1, ADAMTS‐4, ADAMTS‐5, tissue inhibitor of metalloproteinases 1 (TIMP‐1), TIMP‐2, TIMP‐3, and TIMP‐4 were determined in fresh tissue. Results The rate of loss of 35S‐labeled proteoglycans was greater in abnormal tendons, as was the rate of synthesis of proteoglycans. Fluorography and Western blotting revealed the presence of greater amounts of large proteoglycans (aggrecan and versican) in abnormal tendons, and these proteoglycans were rapidly lost from the matrix of abnormal tendons. There was no significant difference in the expression of ADAMTS‐1, ADAMTS‐4, ADAMTS‐5, MMP‐1, MMP‐2, MMP‐3, MMP‐13, TIMP‐2, TIMP‐3, or TIMP‐4. There was a significant increase in the expression of MMP‐9 and TIMP‐1 in abnormal tendons. Conclusion Our findings suggest that a change in the proteoglycan content of the extracellular matrix in abnormal tendons results from the altered metabolism of the cells, reflected in the enhanced synthesis of the large proteoglycans aggrecan and versican, and does not appear to result from changes at the level of gene expression.