Author: ["Danielle Diarra","Marina Stolina","Karin Polzer","Jochen Zwerina","Michael S Ominsky","Denise Dwyer","Adelheid Korb","Josef Smolen","Markus Hoffmann","Clemens Scheinecker","Desiree van der Heide","Robert Landewe","Dave Lacey","William G Richards","Georg Schett"]
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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-α (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.Cite this article
Diarra, D., Stolina, M., Polzer, K. et al. Dickkopf-1 is a master regulator of joint remodeling. Nat Med 13, 156–163 (2007). https://doi.org/10.1038/nm1538 