Abstract: ADAMTS-1, a Gene Product of Articular Chondrocytes in Vivo and in Vitro, Is Downregulated by Interleukin 1ß

ADAMTS-1, a Gene Product of Articular Chondrocytes in Vivo and in Vitro, Is Downregulated by Interleukin 1ß

LYDIA WACHSMUTH, BRIGITTE BAU, ZHIYONG FAN, ANJA PECHT, NICOLE GERWIN, and THOMAS AIGNER

ABSTRACT.

Objective. Osteoarthritic (OA) cartilage degeneration and cartilage destruction in rheumatoid arthritis depends significantly on enzymatic degradation of cartilage proteoglycan aggrecan. A member of the ADAMTS family of proteases, ADAMTS-1 was described to have "aggrecanase" activity. We investigated the quantitative expression and distribution of ADAMTS-1 in healthy and OA cartilage and in cultured articular chondrocytes with and without stimulation by interleukin 1ß (IL-1ß) and insulin-like growth factor-I (IGF-I).

Methods. Conventional and online polymerase chain reaction (PCR) technology was used to determine ADAMTS-1 mRNA expression levels of ADAMTS-1. Protein was localized using immunostaining with different polyclonal antibodies.

Results. Conventional and online semiquantitative PCR showed significant levels of ADAMTS-1 mRNA expression in normal and OA chondrocytes in vivo and in vitro. Only a slight increase was observed in OA cartilage. After stimulation with IL-1ß a downregulation of ADAMTS-1 was observed, whereas IGF did not appear to change mRNA expression levels in vitro. The in vivo mRNA expression results were confirmed by the presence of significant protein staining with antibodies for ADAMTS-1 in normal and OA chondrocytes as well as Western blotting analysis. Whereas a significantly stronger stain was seen in normal articular cartilage in the upper zones, in OA cartilage as well the middle zone showed enhanced staining.

Conclusion. Our results confirm the expression and presence of ADAMTS-1 in articular cartilage. However, they also point out that ADAMTS-1 appears to be constitutively expressed by adult articular chondrocytes and overall is not strongly upregulated in OA. Thus our data suggest that ADAMTS-1 is the first matrix-degrading enzyme downregulated by the catabolic factor IL-1ß in vitro. (J Rheumatol 2004;31:315-20)

Key Indexing Terms:

METALLOPROTEINASES
AGGRECANASE
COLLAGEN
AGGRECAN
OSTEOARTHRITIS
CARTILAGE

From the Cartilage Research Unit, Department of Pathology, University of Erlangen-Nürnberg, Erlangen; and the Osteoarthritis Disease Group, Aventis Pharma Deutschland, Frankfurt, Germany.

Supported by the Ministry of Research, Bonn, Germany (grant 01GG9824).

L. Wachsmuth, PhD; B. Bau, MSc; Z. Fan, MD; A. Pecht, PhD; T. Aigner, MD, University of Erlangen-Nürnberg; N. Gerwin, PhD, Aventis Pharma Deutschland.

Address reprint requests to Dr. T. Aigner, Cartilage Research, Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstrasse 8-10, D-91054 Erlangen, Germany. E-mail: thomas.aigner@patho.imed.uni-erlangen.de

Submitted October 22, 2002; revision accepted June 9, 2003.