ab21208

MMP-8 is only a minor gene product of human adult articular chondrocytes of the knee

S. Stremme, S. Duerr, B. Bau, E. Schmid, T. Aigner

Cartilage Research, Department of Pathology, University of Erlangen, Nürnberg,
Germany

ABSTRACT
Objective
The initial degradation of collagen fibrils during osteoarthritic cartilage destruction depends on the cleavage at the collagenase site, for which there exist three major candidate enzymes: collagenase 1 (MMP-1), collagenase 2 (MMP-8), and collagenase 3 (MMP-13). The objective of this study was to determine the quantitative expression as well as distribution levels in normal and osteoarthritic cartilage and synovium 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-8 expression levels on the mRNA and protein level.

Results
Whereas conventional PCR analysis could demonstrate the presence of MMP-8 mRNA in normal and osteoarthritic chondrocytes, online quantitative PCR showed that only very minor amounts of MMP-8 mRNA expression is found in articular chondrocytes in vivo (and in vitro) and that there is no significant upregulation in osteoarthritic cartilage in vivo nor by Il-1b in vitro. The in vivo results were confirmed by the absence of significant protein staining with monoclonal antibodies for MMP-8 in normal and osteoarthritic chondrocytes.

Conclusions
The presented results confirm the presence of a very minor MMP-8 expression by articular chondrocytes, but clearly question the hypothesis that MMP-8 is a major cartilage matrix degrading protease and is involved in enhanced cartilage matrix breakdown in osteoarthritic cartilage degeneration or by Il-1b stimulation in vitro.

Key words
Metalloproteinases, aggrecanase, collagenase, collagen, osteoarthritis, cartilage.

Sebastian Stremme*, MD; Stefan Duerr*, MD; Brigitte Bau, MD; Erik Schmid, MD; Thomas Aigner. *These authors contributed equally to the work.
This work was supported by the Ministry of Research (grant 01GG9824).
Please address correspondence and reprint requests to: Thomas Aigner, MD, Cartilage Research, Department of Pathology, University of Erlangen-NŸrnberg, Krankenhausstrasse 8-10, D-91054 Erlangen, Germany.
E-mail: thomas.aigner@patho.imed.uni-erlangen.de