Document Detail

Bone morphogenetic protein receptor IB signaling mediates apoptosis independently of differentiation in osteoblastic cells.
MedLine Citation:
PMID:  14576167     Owner:  NLM     Status:  MEDLINE    
Bone morphogenetic protein-2 (BMP-2) is an important regulator of osteoblast differentiation. However, the regulation of osteoblast apoptosis by BMP signaling remains poorly understood. Here we examined the role of type I BMP receptor (BMP-RI) in osteoblast apoptosis promoted by BMP-2. Despite undetectable BMP-RIB expression in OHS4 cells, BMP-2 or BMP-2 overexpression increased osteoblast differentiation similarly as in SaOS2 cells which express BMP-RIB, as shown by alkaline phosphatase and CBFA1/RUNX2 expression. In contrast to SaOS2 cells, however, BMP-2 or BMP-2 overexpression did not increase caspase-9 and caspases-3, -6, and -7 activity and DNA fragmentation in OHS4 cells. Consistently, BMP-2 increased protein kinase C (PKC) activity, and PKC inhibition suppressed BMP-2-induced caspase activity in SaOS2 but not in OHS4 cells that lack BMP-RIB. A dominant negative BMP-RIB inhibited BMP-2-induced caspase activity, whereas wild-type BMP-RIB promoted caspase activity induced by BMP-2 in SaOS2 and MC3T3-E1 cells. Wild-type BMP-RIB rescued the apoptotic response to BMP-2, and a constitutively active BMP-RIB restored the apoptotic signal in OHS4 cells, supporting an essential role for BMP-RIB in osteoblast apoptosis. We also assessed whether BMP-2-induced apoptosis occurred independently of osteoblast differentiation. General inhibition of caspases did not abolish BMP-2-induced alkaline phosphatase and CBFA1/RUNX2 expression in SaOS2 cells. Furthermore, broad caspases inhibition increased matrix mineralization but did not reverse the BMP-2 effect on mineralization in MC3T3-E1 cells. These results indicate that BMP-2-induced apoptosis was mediated by BMP-RIB in osteoblasts and occurred independently of BMP-2-induced osteoblast differentiation, which provides additional insights into the dual mechanism of BMP-2 action on osteoblast fate.
Eric Haÿ; Jérome Lemonnier; Olivia Fromigué; Hind Guénou; Pierre J Marie
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-10-23
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-12     Completed Date:  2004-02-12     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1650-8     Citation Subset:  IM    
Laboratory of Osteoblast Biology and Pathology, INSERM U 349, CNRS, Lariboisière Hospital, 75475 Cedex 10 Paris, France.
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MeSH Terms
Bone Morphogenetic Protein 2
Bone Morphogenetic Protein Receptors, Type I
Bone Morphogenetic Proteins / pharmacology
Caspases / physiology
Cell Differentiation
Cell Line, Tumor
Gene Expression / drug effects
Osteoblasts / cytology*,  metabolism
Protein Kinase C / physiology
Protein-Serine-Threonine Kinases / physiology*
Receptors, Growth Factor / physiology*
Transforming Growth Factor beta*
Reg. No./Substance:
0/BMP2 protein, human; 0/Bone Morphogenetic Protein 2; 0/Bone Morphogenetic Proteins; 0/Receptors, Growth Factor; 0/Transforming Growth Factor beta; EC Kinases; EC Kinase C; EC protein, human; EC Morphogenetic Protein Receptors, Type I; EC 3.4.22.-/Caspases

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