help button home button Am J Pathol International Conference on Pathology of Chest Diseases
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2008.080243 on August 1, 2008 Originally published online as doi:10.2353/ajpath.2008.080243 on July 31, 2008

Published online before print July 31, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
ajpath.2008.080243v1
ajpath.2008.080243v2
173/3/773    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
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
Google Scholar
Right arrow Articles by Samee, N.
Right arrow Articles by de Vernejoul, M.-C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Samee, N.
Right arrow Articles by de Vernejoul, M.-C.
(American Journal of Pathology. 2008;173:773-780.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.080243

Dlx5, a Positive Regulator of Osteoblastogenesis, is Essential for Osteoblast-Osteoclast Coupling

Nadeem Samee*{dagger}, Valerie Geoffroy*, Caroline Marty*, Corinne Schiltz*, Maxence Vieux-Rochas{dagger}, Giovanni Levi{dagger},{ddagger} and Marie-Christine de Vernejoul*,{ddagger}

From the INSERM U606,* Hôpital Lariboisière, Paris, France; CNRS UMR5166,{dagger} Evolution des Régulations Endocriniennes, MNHN, Paris, France

The homeodomain protein Dlx5 is an activator of Runx2 (a key regulator of osteogenesis) and is thought to be an important regulator of bone formation. At present, however, the perinatal lethality of Dlx5-null mice has hampered the elucidation of its function in osteogenesis. Here we provide the first analysis of the effects of Dlx5 inactivation on bone development. Femurs of Dlx5-null mouse embryos at the end of gestation exhibit a reduction in both total and trabecular bone volume associated with increased trabecular separation and reduced trabecular number. These parameters are often associated with pathological conditions characterized by reduced osteoblast activity and increased bone resorption. Dlx5–/– osteoblasts in culture display reduced proliferation and differentiation rate and reduction of Runx2, Osx, Osteocalcin and Bone Sialoprotein expression. In addition to impaired osteoblast function, Dlx5–/– femurs exhibit significant increases in osteoclast number. As Dlx5 is not expressed by osteoclasts, we suggest that its osteoblastic expression might control osteoblast/osteoclast coupling. Cultured Dlx5–/– osteoblasts displayed a higher RANKL/OPG ratio. Furthermore, Dlx5–/– osteoblasts induced a higher number of TRAP-positive multinucleated cells in normal spleen cultures with a globally increased resorption activity. These findings suggest that Dlx5 is a central regulator of bone turnover as it activates bone formation directly and bone resorption indirectly.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American Society for Investigative Pathology.