Volume 28, Issue 4, December 2017

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Mediterr J Rheumatol 2017; 28(4):20-8
Dkk1: A key molecule in joint remodelling and fibrosis
Authors Information
Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece

Dickkopf-1 (Dkk-1) is a Wnt signaling pathway inhibitor that has been shown to play an important role in joint remodeling, in experimental models of arthritis and in humans. Recent data suggest that this molecule is involved in the fibrotic process as well. OBJECTIVES: This review summarizes all the available data regarding the role of Dkk-1 in joint remodeling and fibrosis. METHODS: An electronic search in literature was performed using the terms Dickkopf-1 (Dkk-1), fibrosis, Systemic Sclerosis (Scleroderma), joint remodeling, Ankylosing Spondylitis. Moreover, references in the retrieved articles were reviewed. RESULTS: Dkk1 expression seems to determine the fate of an arthritic joint, shifting the process of joint remodelling towards either an erosive/destructive phenotype, when Dkk1 is overexpressed or new bone formation when its expression is decreased. In humans, evidence suggests that Dkk-1 may be dysfunctional in patients with ankylosing spondylitis. Moreover, data from animal models indicate that Dkk-1 may be crucially involved in the fibrotic process in several organs such as the liver, lungs and kidneys. In animal models, enhanced expression of Dkk-1 had a clear suppressive effect on fibrosis suggesting that this molecule could be an attractive target in fibrotic diseases. In humans, Dkk-1 is clearly expressed in the skin. However, in patients with systemic sclerosis Dkk-1 is strikingly absent from the skin. CONCLUSION: Dkk-1 plays a critical role in joint remodeling and fibrosis and could serve as either a biomarker in diseases characterized by pathological joint remodeling or as a potential therapeutic target in fibrotic diseases.