Participation of transglutaminase in the activation of latent transforming growth factor beta1 in aging articular cartilage. Arthritis Rheum 2000 Aug;43(8):1729-33
Date
08/16/2000Pubmed ID
10943862DOI
10.1002/1529-0131(200008)43:8<1729::AID-ANR8>3.0.CO;2-0Scopus ID
2-s2.0-0033869479 (requires institutional sign-in at Scopus site) 44 CitationsAbstract
OBJECTIVE: Transglutaminase (TGase) catalyzes the calcium-dependent crosslinking of polypeptide chains, resulting in posttranslational protein modifications that affect both intracellular and extracellular processes. We previously demonstrated a dramatic elevation of TGase activity levels in aging articular chondrocytes and postulated a role for TGase in the pathologic processes common in aging joints. In several cell systems, TGase participates in the activation of latent transforming growth factor beta (LTGFbeta). Since TGFbeta is a key factor in age-related cartilage diseases, the purpose of the present study was to determine whether TGase from aging articular chondrocytes participates in LTGFbeta activation.
METHODS: We measured the ability of old and young porcine articular chondrocytes to activate 10 ng/ml of LTGFbeta1 in the presence and absence of TGase inhibitors. The activity of plasmin, another key participant in LTGFbeta activation, was also measured.
RESULTS: Old chondrocytes activated 11+/-1.8% (mean +/- SD) of exogenous LTGFbeta1 at 6 hours, while young chondrocytes activated 4.2+/-0.5% of exogenous LTGFbeta1. The addition of 3 different TGase inhibitors suppressed active TGFbeta1 in the cell layer to levels that were 35-69% of control values in old chondrocytes and had no effect on young chondrocytes. The ability to suppress TGFbeta activation correlated with the ability of each of the TGase inhibitors to inhibit TGase activity. The activity of plasmin, which enzymatically activates LTGFbeta1, did not differ between young and old chondrocytes and was unaffected by TGase inhibition.
CONCLUSION: We report here a novel pathologic function for TGase in aging articular cartilage. This work supports a role for elevated TGase activity in age-related arthritis based in part on its participation in the activation of the critical growth factor TGFbeta in articular cartilage.
Author List
Rosenthal AK, Gohr CM, Henry LA, Le MAuthor
Ann K. Rosenthal MD Associate Dean, Chief, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgingAnimals
Cartilage, Articular
Enzyme Inhibitors
Fibrinolysin
Swine
Transforming Growth Factor beta
Transglutaminases