The role of Dickkopf-1 in joint remodeling and fibrosis: A link connecting spondyloarthropathies and scleroderma?
Dickkopf-1 (Dkk-1) is a soluble inhibitor of the canonical Wnt pathway, which plays critical roles in embryonic development. Evidence suggests that this molecule regulates several aspects of both bone biology and fibrosis.



To provide an overview of our current knowledge of the role of Dkk-1 in joint remodeling and fibrosis.



We performed an electronic search (Medline) using the following key words: Dickkopf-1 (or Dkk-1), new bone formation, joint remodeling, ankylosing spondylitis, systemic sclerosis (or scleroderma), and fibrosis, supplemented by a manual search of references from retrieved articles.



Dkk-1 is a master regulator of joint remodeling in animal models of arthritis shifting the balance toward new bone formation when its expression is decreased and toward erosion/joint destruction when its expression is increased. In humans, evidence suggests that Dkk-1 may be dysfunctional in patients with ankylosing spondylitis, a prototype bone forming disease. Moreover, data from animal models indicate that Dkk-1 has a protective role against fibrosis in several organs. Recent data suggest that inhibiting the canonical Wnt pathway by overexpression of Dkk-1 could be a way to target TGF-β signaling in fibrotic diseases. Finally, B-cell depletion therapy in systemic sclerosis may exert its effects through TGF-β dependent upregulation of Dkk-1.



Dkk-1 appears to play a crucial role in both joint remodeling/ectopic ossification and fibrosis, and may be a prospective therapeutic modality for fibrotic diseases or diseases characterized by pathologic joint remodeling.
Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
Kalliopi
K
Klavdianou
Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
Stamatis-Nick
SN
Liossis
Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Lazaros
L
Sakkas
Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece. Electronic address: jimdaoussis@hotmail.com.
Dimitrios
D
Daoussis
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D016723:Bone Remodeling / Q000235:genetics; D005355:Fibrosis / Q000235:genetics* / Q000276:immunology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000276:immunology; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology; D025242:Spondylarthropathies / Q000235:genetics / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology; D060449:Wnt Signaling Pathway
C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta
Ankylosing spondylitis; Dickkopf-1; Dkk-1; Joint remodeling; New bone formation; Scleroderma and fibrosis; Systemic sclerosis