Faculty Collaboration Database

Transglutaminase participates in the incorporation of latent TGFbeta into the extracellular matrix of aging articular chondrocytes. Connect Tissue Res 2001;42(4):245-53

Date

03/27/2002

Pubmed ID

11913769

DOI

10.3109/03008200109016839

Scopus ID

2-s2.0-0035215305 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

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.

Author List

Le M, Gohr CM, Rosenthal AK

Author

Ann K. Rosenthal MD Associate Dean, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cadaverine
Cartilage, Articular
Cells, Cultured
Cellular Senescence
Chondrocytes
Cystamine
Enzyme Inhibitors
Extracellular Matrix
Fibronectins
Swine
Tissue Distribution
Transforming Growth Factor beta
Transglutaminases