Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy.
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 (35)S-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.


CONCLUSIONS
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.
La Trobe University, Melbourne, Victoria, Australia.
John
J
Parkinson
Tom
T
Samiric
Mirna Z
MZ
Ilic
Jill
J
Cook
Julian A
JA
Feller
Christopher J
CJ
Handley
D053674:Aggrecans / Q000378:metabolism*; D016022:Case-Control Studies; D020869:Gene Expression Profiling; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D017847:Patellar Ligament / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D052256:Tendinopathy / Q000378:metabolism*; D046509:Tissue Culture Techniques; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*; D053675:Versicans / Q000378:metabolism*
D053674:Aggrecans; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D053675:Versicans; D020780:Matrix Metalloproteinase 9