Dickkopf-1 is a master regulator of joint remodeling

被引：1153

作者：

Diarra, Danielle

Stolina, Marina

Polzer, Karin

Zwerina, Jochen

Ominsky, Michael S.

Dwyer, Denise

Korb, Adelheid

Smolen, Josef

Hoffmann, Markus

Scheinecker, Clemens

van der Heide, Desiree

Landewe, Robert

Lacey, Dave

Richards, William G.

Schett, Georg

机构：

[1] Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany

[2] Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany

[3] Med Univ Vienna, Dept Internal Med 3, Div Rheumatol, A-1090 Vienna, Austria

[4] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA

[5] Univ Hosp Maastricht, Dept Internal Med & Rheumatol, NL-6229 HX Maastricht, Netherlands

来源：

NATURE MEDICINE | 2007年 / 13卷 / 02期

基金：

奥地利科学基金会;

关键词：

D O I：

10.1038/nm1538

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

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-alpha (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.

引用

页码：156 / 163

页数：8

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