M. D. Tortorella, ¹ T. C. Burn, ² M. A. Pratta, ¹ I. Abbaszade, ² J. M. Hollis, ² R. Liu, ¹ S. A. Rosenfeld, ² R. A. Copeland, ³ C. P. Decicco, ⁴ R. Wynn, ² A. Rockwell, ⁴ F. Yang, ³ J. L. Duke, ² K. Solomon, ¹ H. George, ² R. Bruckner, ¹ H. Nagase, ⁵ Y. Itoh, ^5* D. M. Ellis, ² H. Ross, ² B. H. Wiswall, ² K. Murphy, ² M. C. Hillman Jr., ² G. F. Hollis, ² R. C. Newton, ¹ R. L. Magolda, ¹ J. M. Trzaskos, ¹ E. C. Arner ¹

We purified, cloned, and expressed aggrecanase, a protease that is thought to be responsible for the degradation of cartilage aggrecan in arthritic diseases. Aggrecanase-1 [a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)] is a member of the ADAMTS protein family that cleaves aggrecan at the glutamic acid-373-alanine-374 bond. The identification of this protease provides a specific target for the development of therapeutics to prevent cartilage degradation in arthritis.

¹ Department of Inflammatory Diseases Research,
² Department of Applied Biotechnology,
³ Department of Enzymology,
⁴ Department of Chemical and Physical Sciences, DuPont Pharmaceuticals Company, Wilmington, DE 19880-0400, USA.
⁵ Department of Biochemistry and Molecular Biology, University of Kansas School of Medicine, Kansas City, KS 66160, USA.
^*   Present address: Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.

   To whom correspondence should be addressed. E-mail: elizabeth.c.arner{at}dupontpharma.com