title: Dickkopf-1 is a master regulator of joint remodeling.
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-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.
authors.affiliation: Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nurnberg, Krankenhausstrasse 12, D-91054 Erlangen, Germany.
authors.forename: Danielle
authors.initials: D
authors.lastname: Diarra
authors.forename: Marina
authors.initials: M
authors.lastname: Stolina
authors.forename: Karin
authors.initials: K
authors.lastname: Polzer
authors.forename: Jochen
authors.initials: J
authors.lastname: Zwerina
authors.forename: Michael S
authors.initials: MS
authors.lastname: Ominsky
authors.forename: Denise
authors.initials: D
authors.lastname: Dwyer
authors.forename: Adelheid
authors.initials: A
authors.lastname: Korb
authors.forename: Josef
authors.initials: J
authors.lastname: Smolen
authors.forename: Markus
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Clemens
authors.initials: C
authors.lastname: Scheinecker
authors.forename: Desiree
authors.initials: D
authors.lastname: van der Heide
authors.forename: Robert
authors.initials: R
authors.lastname: Landewe
authors.forename: Dave
authors.initials: D
authors.lastname: Lacey
authors.forename: William G
authors.initials: WG
authors.lastname: Richards
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000032:analysis; D006801:Humans; D007118:Immunoassay; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013582:Synovial Fluid / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D015675:Osteocalcin