Faculty Collaboration Database

Transglutaminase activity in aging articular chondrocytes and articular cartilage vesicles. Arthritis Rheum 1997 May;40(5):966-70

Date

05/01/1997

Pubmed ID

9153560

DOI

10.1002/art.1780400526

Scopus ID

2-s2.0-0030916270 (requires institutional sign-in at Scopus site)   71 Citations

Abstract

OBJECTIVE: Transglutaminases (TGases) (E.C. 2.3.2.13) catalyze a posttranslational modification of proteins and are associated with biomineralization in growth plate cartilage. Type II TGase participates in the activation of latent transforming growth factor beta (TGFbeta), a crucial factor for both normal cartilage mineralization and the pathologic mineralization that results in calcium pyrophosphate dihydrate (CPPD) crystal formation in aging articular cartilage. To explore a possible association between TGase levels and CPPD crystal formation in mature articular cartilage, TGase activity in articular chondrocytes from old and young pigs and in the articular cartilage vesicle (ACV) fraction of porcine articular cartilage was examined. In addition, the effects of TGase inhibitors on the production of inorganic pyrophosphate (PPi), a process necessary for CPPD crystallogenesis, were determined.

METHODS: TGase activity was measured with a radiometric assay in cultured articular chondrocytes from the knee joints of old (3-5 years old) and young (2-6 weeks old) pigs and in the ACVs. PPi levels were measured in chondrocyte-conditioned media in the presence of TGase inhibitors or control compounds.

RESULTS: Levels of TGase activity in the cytosolic fraction of old chondrocytes were 7-fold higher than those in identically cultured young chondrocytes. The mean +/- SD activity level in the membrane fraction of lysed chondrocytes was 6.0 +/- 0.6 units/mg protein in old articular chondrocytes and was undetectable in young chondrocytes. In ACVs, the mean +/- SD TGase activity level was 1.23 +/- 0.1 units/mg protein. Type II TGase protein was present in chondrocyte cytosol and in ACVs. TGase activity was increased by TGFbeta to 120% of control values (P < 0.01), and decreased by insulin-like growth factor 1 to 80% of control values (P < 0.01). TGase inhibitors blocked media accumulation of PPi, an essential precursor of CPPD crystal formation, and a sensitive marker of TGFbeta effect.

CONCLUSION: These data suggest a potential link between TGase activity and processes of pathologic biomineralization that result in CPPD crystal formation in aging articular cartilage.

Author List

Rosenthal AK, Derfus BA, Henry LA

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

Aging
Aminoacetonitrile
Animals
Cadaverine
Cartilage, Articular
Cystamine
Diphosphates
Enzyme Inhibitors
Growth Substances
Hydrolysis
Methylhistamines
Swine
Transglutaminases