Transglutaminase participates in the incorporation of latent TGFbeta into the extracellular matrix of aging articular chondrocytes.
TGFbeta1 is a multifunctional peptide growth factor that promotes processes associated with age-related degenerative diseases in articular cartilage. Large quantities of TGFbeta1 are stored in cartilage extracellular matrix (ECM) in a latent form (LTGFbeta1), and yet little is known about the factors that participate in the incorporation of LTGFbeta1 into the highly specialized cartilage ECM. We previously demonstrated high levels of the protein cross-linking enzyme transglutaminase (TGase) in aging articular chondrocytes and showed that this enzyme participated in LTGFbeta1 activation. This work explores the hypothesis that extracellular TGase participates in LTGFbeta1 incorporation into ECM in aging chondrocytes. We studied the effects of TGase inhibitors on TGFbeta1 levels in ECM of old and young porcine articular chondrocytes. TGase inhibitors decreased the quantity of LTGFbeta1 in the ECM in old but not in young chondrocytes to 60-70% of control values (p<.05). Fibronectin, an extracellular TGase competitive substrate, also decreased LTGFbeta1 levels in ECM (p<.01). Levels of activated TGFbeta1 also decreased in the presence of TGase inhibitors, as did levels of latent TGFbeta binding protein 1 in the cell layer. Extracellular TGase activity was present in old but not young chondrocyte cultures. These findings support a role for extracellular TGase in the incorporation of LTGFbeta1 in the ECM of aging chondrocytes.
Le
M
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Division of Rheumatology, Department of Medicine, Medical College of Wisconsin, Milwaukee 53295, USA.
Gohr
C M
CM
Rosenthal
A K
AK
D000818:Animals; D002103:Cadaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D019902:Chondrocytes / Q000378:metabolism*; D003538:Cystamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000494:pharmacology; D013552:Swine; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine; D003538:Cystamine