The Emerging Role of Dickkopf-1 in Bone Biology: Is It the Main Switch Controlling Bone and Joint Remodeling?

Background: Dickkopf-1 (DKK-1), an inhibitor of the Wnt pathway, has recently emerged as an important player in several critical aspects of bone biology. Methods: We performed an extensive internet search (MEDLINE) using the key words Dickkopf-1 and the abbreviation DICK-1. Results: DKK-1 is a regulator of bone mass with increased expression linked to osteopenia and decreased expression to high bone mass. Moreover, it appears to actively participate in joint remodeling in animal models of arthritis, with increased levels related to bone resorption and decreased levels to new bone formation. Recent studies indicate its possible involvement in the remodeling process of human systemic rheumatic diseases such as rheumatoid arthritis and ankylosing spondylitis. DKK-1 may also play a role in osteoarthritis, metabolic bone disease (osteoporosis and Paget's disease), as well as multiple myeloma-associated bone disease and prostate cancer bone metastases. Conclusions: DKK-1 is a regulator of bone mass and joint remodeling. It may be a promising therapeutic target in osteoporosis; monoclonal antibody-based inhibition of Dkk-1 is already under development for osteoporosis treatment. Its role as a regulator of joint remodeling in animal models requires further exploration in humans. (C) 2011 Elsevier Inc. All rights reserved. Semin Arthritis Rheum 41:170-177