Klavdianou Kalliopi, Liossis Stamatis-Nick, Daoussis Dimitrios
Department of Rheumatology, University of Patras Medical School, Patras University Hospital, Patras, Greece.
Mediterr J Rheumatol. 2017 Dec 22;28(4):174-182. doi: 10.31138/mjr.28.4.174. eCollection 2017 Dec.
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.
This review summarizes all the available data regarding the role of Dkk-1 in joint remodeling and fibrosis.
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.
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.
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.
Dickkopf-1（Dkk-1）是一种Wnt信号通路抑制剂，已证实在关节炎实验模型和人类中，其在关节重塑中发挥重要作用。近期数据表明，该分子也参与纤维化过程。
本综述总结了关于Dkk-1在关节重塑和纤维化中作用的所有现有数据。
使用Dickkopf-1（Dkk-1）、纤维化、系统性硬化症（硬皮病）、关节重塑、强直性脊柱炎等术语在文献中进行电子检索。此外，还对检索到的文章中的参考文献进行了审查。
Dkk1的表达似乎决定了关节炎关节的命运，当Dkk1过表达时，关节重塑过程会转向侵蚀性/破坏性表型；当其表达降低时，则会转向新骨形成。在人类中，有证据表明强直性脊柱炎患者的Dkk-1可能功能失调。此外，动物模型的数据表明，Dkk-1可能在肝脏、肺和肾脏等多个器官的纤维化过程中起关键作用。在动物模型中，Dkk-1表达增强对纤维化有明显的抑制作用，表明该分子可能是纤维化疾病中有吸引力的靶点。在人类中，Dkk-1在皮肤中明显表达。然而，系统性硬化症患者的皮肤中明显缺乏Dkk-1。
Dkk-1在关节重塑和纤维化中起关键作用，可作为以病理性关节重塑为特征的疾病的生物标志物，或作为纤维化疾病的潜在治疗靶点。
