Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 15 January 2009, Vol. 113, No. 3, pp. 517-525.
Prepublished online as a Blood First Edition Paper on October 3, 2008; DOI 10.1182/blood-2008-03-145169.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2008-03-145169v1
blood-2008-03-145169v2
113/3/517    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pinzone, J. J.
Right arrow Articles by Shaughnessy, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pinzone, J. J.
Right arrow Articles by Shaughnessy, J. D., Jr
Related Collections
Right arrow Lymphoid Neoplasia
Right arrow Review Articles
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

REVIEW ARTICLE

The role of Dickkopf-1 in bone development, homeostasis, and disease

Joseph J. Pinzone1,2, Brett M. Hall3,4, Nanda K. Thudi5, Martin Vonau1, Ya-Wei Qiang6, Thomas J. Rosol2,5, and John D. Shaughnessy, Jr6

1 Department of Internal Medicine, 2 Comprehensive Cancer Center, and 3 Department of Pediatrics, The Ohio State University, Columbus; 4 Center for Childhood Cancer, Columbus Children's Research Institute, OH; 5 Department of Veterinary Sciences, The Ohio State University, Columbus; and 6 Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock

Wnt/β-catenin signaling is central to bone development and homeostasis in adulthood and its deregulation is associated with bone pathologies. Dickkopf-1 (DKK1), a soluble inhibitor of Wnt/β-catenin signaling required for embryonic head development, regulates Wnt signaling by binding to the Wnt coreceptor lipoprotein-related protein-5 (LRP5)/Arrow. LRP5 mutations causing high bone mass syndromes disrupt DKK1-mediated regulation of LRP5. Forced overexpression of Dkk1 in osteoblasts causes osteopenia, disruption of the hematopoietic stem cell (HSC) niche, and defects in HSC function. Dkk1 also inhibits fracture repair. Studies suggest that DKK1 activation in osteoblasts is the underlying cause of glucocorticoid- and estrogen deficiency–mediated osteoporosis, and at least partially underlies the teratogenic effects of thalidomide on limb development. DKK1 induces proliferation of mesenchymal stem cells (MSC) in vitro and may play a role in the development of high-grade undifferentiated pleomorphic sarcomas derived from MSC and osteosarcomas. DKK1 has been implicated in causing erosive arthritis, the osteolytic phenotypes of multiple myeloma and metastatic breast cancer, and osteoblastic metastases of prostate cancer. Preclinical studies have shown that neutralizing DKK1/Dkk1 and/or enhancing Wnt/β-catenin signaling may prove effective in treating bone pathologies. Here, we review the rapidly growing body of literature defining a pivotal role for DKK1 in bone health and disease.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 BloodHome page
A. Kukreja, S. Radfar, B.-H. Sun, K. Insogna, and M. V. Dhodapkar
Dominant role of CD47-thrombospondin-1 interactions in myeloma-induced fusion of human dendritic cells: implications for bone disease
Blood, October 15, 2009; 114(16): 3413 - 3421.
[Abstract] [Full Text] [PDF]

Home page
 haematolHome page
E. Voskaridou, D. Christoulas, C. Xirakia, K. Varvagiannis, G. Boutsikas, A. Bilalis, E. Kastritis, A. Papatheodorou, and E. Terpos
Serum Dickkopf-1 is increased and correlates with reduced bone mineral density in patients with thalassemia-induced osteoporosis. Reduction post-zoledronic acid administration
Haematologica, May 1, 2009; 94(5): 725 - 728.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
Y.-W. Qiang, B. Hu, Y. Chen, Y. Zhong, B. Shi, B. Barlogie, and J. D. Shaughnessy Jr
Bortezomib induces osteoblast differentiation via Wnt-independent activation of {beta}-catenin/TCF signaling
Blood, April 30, 2009; 113(18): 4319 - 4330.
[Abstract] [Full Text] [PDF]


click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020