ab22508

MMP-2/gelatinase A is a gene product of human adult articular chondrocytes and is increased in osteoarthritic cartilage

S. Duerr*, S. Stremme*, S. Soeder, B. Bau, T. Aigner

Osteoarticular and Arthritis Research, Department of Pathology, University of Erlangen-Nürnberg, Germany

ABSTRACT
Objective
Collagen fibril degeneration involves initially the cleavage within the triple helix by the collagenases (1 and 3), but then mainly involves also the gelatinases, of which gelatinase A (MMP-2) appears to play a central role in many tissues. The objective of this study was to determine the quantitative expression levels as well as the distribution in normal and osteoarthritic cartilage of gelatinase A and in cultured articular chondrocytes with and without stimulation by Il-1b.

Methods
Conventional and online PCR technology and immunohistochemistry were used to determine MMP-2 expression levels on the mRNA and protein level.

Results
Conventional PCR analysis could demonstrate the presence of MMP-2 mRNA in normal and osteoarthritic chondrocytes. Online quantitative PCR confirmed the presence of MMP-2 mRNA expression in normal articular chondrocytes in vivo (and in vitro). An increase of 5x (p < 0.001) was observed in osteoarthritic cartilage in vivo. Of note, no significant up-regulation of gelatinase A was observed by Il-1b in vitro. Immunostaining for gelatinase A confirmed the presence of MMP-2 with mono- and polyclonal antibodies in normal and osteoarthritic chondrocytes with somewhat higher levels observed in the latter.

Conclusions
The presented results confirm the increased expression of gelatinase A by osteoarthritic articular chondrocytes as previously described. Of note, also normal adult articular chondrocytes expressed significant amounts of gelatinase A in vivo and in vitro suggesting gelatinase A as being also involved in physiological collagen turnover in human adult articular cartilage.

Key words
Metalloproteinases, gelatinase, collagen degradation, osteoarthritis, cartilage.

*Stephan Duerr and Sebastian Stremme contributed equally to this work.
This work was supported by the Ministry of Research (grant 01GG9824).
Please address correspondence and reprint requests to: Thomas Aigner, MD, DSc, Osteoarticular and Arthritis Research, University of Erlangen-Nürnberg, Krankenhausstrasse 8-10, D-91054 Erlangen, Germany.
E-mail: thomas.aigner@patho.imed.uni-erlangen.de