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Down‐regulation of chondrocyte aggrecan and type‐II Collagen gene expression correlates with increases in static compression magnitude and duration
Author(s) -
Ragan Paula M.,
Badger Alison M.,
Cook Michael,
Chin Vicki I.,
Gowen Maxine,
Grodzinsky Alan J.,
Lark Michael W.
Publication year - 1999
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.1100170608
Subject(s) - aggrecan , type ii collagen , chondrocyte , messenger rna , chemistry , type i collagen , gene expression , cartilage , microbiology and biotechnology , biochemistry , endocrinology , biology , anatomy , osteoarthritis , gene , medicine , pathology , in vitro , articular cartilage , alternative medicine
The goal of this study was to examine the simultaneous effects of mechanical compression of chondrocytes on mRNA expression and macromolecular synthesis of aggrrecan and type‐II collagen. Bovine cartilage explants were exposed to different magnitudes and durations of applied mechanical compression, and levels of aggrecan and type‐IIa collagen mRNA normalized to glyceraldehyde‐3‐phosphate dehydrogenase were measured and quantified by Northern blot analysis. Synthesis of aggrecan and type‐II collagen protein was measured by radiolabel incorporation of [ 35 S]sulfate and [ 3 H]proline into macromolecules. The results showed a dose‐dependent decrease in mRNA levels for aggrecan and type‐II collagen, with increasing compression relative to physiological cut thickness applied for 24 hours. Radiolabel incorporation into glycosaminoglycans and collagen also decreased with increasing compression in a dose‐related manner similar to the changes seen in mRNA expression. The modulation of aggrecan and type‐II collagen mRNA and protein synthesis were dependent on the duration of the compression. Aggrecan and type‐II collagen mRNA expression increased during the initial 0.5 hours of static compression; however, 4‐24 hours after compression was applied total mRNA levels had significantly decreased. The synthesis of aggrecan and collagen protein decreased more rapidly than did mRNA levels after the application of a step compression. Together, these results suggest that mechanical compression rapidly alters chondrocyte aggrecan and type‐II collagen gene expression on application of load. However, our results indicate that the observed decreases in biosynthesis may not be related solely to changes in mRNA expression. The mechanisms by which mechanical forces affect different segments of the biosynthetic pathways remain to be determined.