Article abstract
Nature Medicine 13, 156 - 163 (2007)
Published online: 21 January 2007 | doi:10.1038/nm1538
Dickkopf-1 is a master regulator of joint remodeling
Danielle Diarra1,2,5, Marina Stolina3,5, Karin Polzer1, Jochen Zwerina1, Michael S Ominsky3, Denise Dwyer3, Adelheid Korb2, Josef Smolen2, Markus Hoffmann2, Clemens Scheinecker2, Desiree van der Heide4, Robert Landewe4, Dave Lacey3, William G Richards3 & Georg Schett1,2
Abstract
Degenerative and inflammatory joint diseases lead to a destruction of the joint architecture. Whereas degenerative osteoarthritis results in the formation of new bone, rheumatoid arthritis leads to bone resorption. The molecular basis of these different patterns of joint disease is unknown. By inhibiting Dickkopf-1 (DKK-1), a regulatory molecule of the Wnt pathway, we were able to reverse the bone-destructive pattern of a mouse model of rheumatoid arthritis to the bone-forming pattern of osteoarthritis. In this way, no overall bone erosion resulted, although bony nodules, so-called osteophytes, did form. We identified tumor necrosis factor-
(TNF) as a key inducer of DKK-1 in the mouse inflammatory arthritis model and in human rheumatoid arthritis. These results suggest that the Wnt pathway is a key regulator of joint remodeling.
- Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nurnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
- Division of Rheumatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
- Department of Metabolic Disorders, Amgen Inc., 1 Amgen Center Drive, Thousand Oaks, California 91320, USA.
- Department of Internal Medicine and Rheumatology, University Hospital Maastricht, P. Debyelaan 25, 6229 HX, Maastricht, The Netherlands.
- These authors contributed equally to this work.
Correspondence to: e-mail: georg.schett@med3.imed.uni-erlangen.de
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