Title
TGF-<tex>$\beta$</tex> 1-induced migration of bone mesenchymal stem cells couples bone resorption with formationTGF-<tex>$\beta$</tex> 1-induced migration of bone mesenchymal stem cells couples bone resorption with formation
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Medical genetics of obesity and skeletal disorders (MGENOS)
Publication type
article
Publication
London,
Subject
Biology
Human medicine
Source (journal)
Nature medicine. - London, 1995, currens
Volume/pages
15(2009):7, p. 757-765
ISSN
1078-8956
1546-170X
ISI
000267806900028
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Bone remodeling depends on the precise coordination of bone resorption and subsequent bone formation. Disturbances of this process are associated with skeletal diseases, such as Camurati-Engelmann disease (CED). We show using in vitro and in vivo models that active TGF-1 released during bone resorption coordinates bone formation by inducing migration of bone marrow stromal cells, also known as bone mesenchymal stem cells, to the bone resorptive sites and that this process is mediated through a SMAD signaling pathway. Analyzing mice carrying a CED-derived mutant TGFB1 (encoding TGF-1), which show the typical progressive diaphyseal dysplasia seen in the human disease, we found high levels of active TGF-1 in the bone marrow. Treatment with a TGF- type I receptor inhibitor partially rescued the uncoupled bone remodeling and prevented the fractures. Thus, as TGF-1 functions to couple bone resorption and formation, modulation of TGF-1 activity could be an effective treatment for bone remodeling diseases.
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