The Journal of Experimental Medicine
R&D Systems
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 15 March 2004. doi:10.1084/jem.20031454
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 6, 805-814
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
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 van Bezooijen, R. L.
Right arrow Articles by Löwik, C. W.G.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Bezooijen, R. L.
Right arrow Articles by Löwik, C. W.G.M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Sclerostin Is an Osteocyte-expressed Negative Regulator of Bone Formation, But Not a Classical BMP Antagonist

Rutger L. van Bezooijen1, Bernard A.J. Roelen2, Annemieke Visser1, Lianne van der Wee-Pals1, Edwin de Wilt1, Marcel Karperien1, Herman Hamersma3, Socrates E. Papapoulos1, Peter ten Dijke2, and Clemens W.G.M. Löwik1

1 Department of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, Netherlands
2 Division of Cellular Biochemistry, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands
3 Department of Otolaryngology, Weltevreden Park 1715, South Africa

Address correspondence to R.L. van Bezooijen, Dept. of Endocrinology, C4-R, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands. Phone: 31-71-5263076; Fax: 31-71-5248136; email: R.L.van_Bezooyen{at}lumc.nl

Sclerosteosis, a skeletal disorder characterized by high bone mass due to increased osteoblast activity, is caused by loss of the SOST gene product, sclerostin. The localization in bone and the mechanism of action of sclerostin are not yet known, but it has been hypothesized that it may act as a bone morphogenetic protein (BMP) antagonist. We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483). Although sclerostin shares some of the actions of the BMP antagonist noggin, we show here that it also has actions distinctly different from it. In contrast to noggin, sclerostin did not inhibit basal alkaline phosphatase (ALP) activity in KS483 cells, nor did it antagonize BMP-stimulated ALP activity in mouse C2C12 cells. In addition, sclerostin had no effect on BMP-stimulated Smad phosphorylation and direct transcriptional activation of MSX-2 and BMP response element reporter constructs in KS483 cells. Its unique localization and action on osteoblasts suggest that sclerostin may be the previously proposed osteocyte-derived factor that is transported to osteoblasts at the bone surface and inhibits bone formation.

Key Words: sclerosteosis • SOST • osteoblast • Smad phosphorylation • MSC

Portions of this work were presented at the 24th Annual Meeting of the American Society for Bone and Mineral Research in San Antonio, TX on 20–24 September 2002.

Abbreviations used in this paper: ALP, alkaline phosphatase; BMP, bone morphogenetic protein; BRE, BMP response element; CoM, control medium; MSC, mesenchymal stromal cell; PTHrP, parathyroid hormone-related protein; SF9, Spodoptera frugiperda.


Add to CiteULike CiteULike   Add to Complore Complore   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 | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS