Dimitrios Daoussis1, Andrew P Andonopoulos. 1. Division of Rheumatology, Department of Internal Medicine, Patras University Hospital, University of Patras Medical School, Patras, Greece. jimdaoussis@hotmail.com
Abstract
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 DKK-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.
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 DKK-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.
Authors: Casey T Kraft; Shailesh Agarwal; Kavitha Ranganathan; Victor W Wong; Shawn Loder; John Li; Matthew J Delano; Benjamin Levi Journal: J Trauma Acute Care Surg Date: 2016-01 Impact factor: 3.313