Preferential mRNA expression of prostromelysin relative to procollagenase and in situ localization in human articular cartilage.
An imbalance between extracellular proteinases and their inhibitors is thought to underlie cartilage degradation. In cultures of adult cartilage, prostromelysin mRNA levels were much higher than those for procollagenase and this differential was increased in cultures stimulated with IL-1 beta. Analysis of mRNA prepared from freshly isolated chondrocytes showed abundant amounts of prostromelysin mRNA in normal adult cartilage but low levels in the neonate. Not all adult cartilage may possess such high levels of prostromelysin mRNA, as the message levels in the cartilage remaining on late-stage osteoarthritic joints were lower than those in normal adult cartilage. Relative to prostromelysin mRNA, little procollagenase and TIMP mRNA were found in the adult cartilage. In situ hybridization revealed that metalloproteinase mRNAs were localized in chondrocytes of the superficial zone in adult cartilage. However, upon IL-1 beta treatment, chondrocytes in all cartilage zones were observed to express prostromelysin mRNA. Relative to the neonate, the normal adult cartilage appears to have a high degradative potential, if one accepts that steady-state mRNA levels reflect prostromelysin production. As the adult cartilage is not apparently undergoing rapid turnover, it would appear that control of prostromelysin activation may be the major regulatory step in stromelysin-induced cartilage degradation.
Nguyen
Q
Q
Joint Diseases Laboratory, Shriners Hospital for Crippled Children, Montreal, Quebec, Canada.
Mort
J S
JS
Roughley
P J
PJ
D000368:Aged; D001483:Base Sequence; D002358:Cartilage, Articular / Q000378:metabolism*; D002478:Cells, Cultured; D017364:Collagenases; D004792:Enzyme Precursors / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007223:Infant; D007375:Interleukin-1 / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics*; D003012:Microbial Collagenase / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis* / Q000096:biosynthesis; D019714:Tissue Inhibitor of Metalloproteinases
D004792:Enzyme Precursors; D006023:Glycoproteins; D007375:Interleukin-1; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D008666:Metalloendopeptidases; C022440:procollagenase; C048047:prostromelysin; D003012:Microbial Collagenase