sost and dkk antagonists of lrp family signaling as targets for treating bone disease苏斯特和dkk拮抗剂单体家族信号作为治疗骨疾病的目标.pdfVIP

SAGE-Hindawi Access to Research Journal of Osteoporosis Volume 2010, Article ID 460120, 9 pages doi:10.4061/2010/460120 Review Article SOST and DKK: Antagonists of LRP Family Signaling as Targets for Treating Bone Disease James J. Mason1, 2 and Bart O. Williams1, 3 1 Center for Skeletal Disease Research, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA 2 Laboratory of Orthopaedic Cell and Tissue Mechanics, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA 3 Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick NE, Grand Rapids, MI 49503, USA Correspondence should be addressed to Bart O. Williams, bart.williams@ Received 3 February 2010; Revised 27 April 2010; Accepted 26 May 2010 Academic Editor: Michael Lewiecki Copyright © 2010 J. J. Mason and B. O. Williams. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The study of rare human genetic disorders has often led to some of the most significant advances in biomedical research. One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. Point mutations were identified that encoded forms of LRP5 associated with very high bone mass (HBM). HBM patients live to a normal age and do not appear to have increased susceptibility to carcinogenesis or other disease. Thus, devising methods to mimic the molecular consequences of this mutation to treat bone diseases associated with low bone mass is a promising avenue to pursue. Two groups of age