JCB logo
PeproTech: Free Shipping at www.peprotech.com
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1083/jcb.200703113
The Journal of Cell Biology, Vol. 178, No. 1, 121-128
The Rockefeller University Press, 0021-9525 $30.00
© Zheng et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1727K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
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 JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zheng, L.
Right arrow Articles by Justice, M. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zheng, L.
Right arrow Articles by Justice, M. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Article

Filamin B represses chondrocyte hypertrophy in a Runx2/Smad3-dependent manner



Lihua Zheng1,2, Hwa-Jin Baek1, Gerard Karsenty2, and Monica J. Justice1

1 Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030
2 Department of Genetics and Development, Columbia University, College of Physicians and Surgeons, New York, NY 10032

Correspondence to Monica J. Justice: mjustice{at}bcm.tmc.edu

FILAMIN B, which encodes a cytoplasmic actin binding protein, is mutated in several skeletal dysplasias. To further investigate how an actin binding protein influences skeletogenesis, we generated mice lacking intact Filamin B. As observed in spondylocarpotarsal synostosis syndrome patients, Filamin B mutant mice display ectopic mineralization in many cartilaginous elements. This aberrant mineralization is due to ectopic chondrocyte hypertrophy similar to that seen in mice expressing Runx2 in chondrocytes. Accordingly, removing one copy of Runx2 rescues the Filamin B mutant phenotype, indicating that Filamin B is a regulator of Runx2 function during chondrocyte differentiation. Filamin B binds Smad3, which is known to interact with Runx2. Smad3 phosphorylation is increased in the mutant mice. Thus, Filamin B inhibits Runx2 activity, at least in part, through the Smad3 pathway. Our results uncover the involvement of actin binding proteins during chondrogenesis and provide a molecular basis to a human genetic disease.

Abbreviations used in this paper: E, embryonic day; ES, embryonic stem; Ihh, Indian hedgehog; Mmp13, matrix metalloproteinase 13; P, postnatal day; Ppr, parathyroid hormone–related peptide receptor; SSS, spondylocarpotarsal synostosis syndrome.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents