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Bone Morphogenetic Proteins Signal Via SMAD and Mitogenactivated Protein (MAP) Kinase Pathways at Distinct Times during Osteoclastogenesis.

Authors :
Broege, Aaron
Pham, Lan
Jensen, Eric D.
Emery, Ann
Tsang-Hai Huang
Stemig, Melissa
Beppu, Hideyuki
Petryk, Anna
O'Connor, Michael
Mansky, Kim
Gopalakrishnan, Raj
Source :
Journal of Biological Chemistry. 12/27/2013, Vol. 288 Issue 52, p37230-37240. 11p.
Publication Year :
2013

Abstract

To investigate the role of bone morphogenetic protein (BMP) signaling in osteoclastogenesis in vivo, we eliminated BMPRII in osteoclasts by creating a BMPRIIfl/fl;lysM-Cre mouse strain. Conditional knock-out (cKO) mice are osteopetrotic when compared with WT controls due to a decrease in osteoclast activity. Bone marrow macrophages (BMMs) isolated from cKOmice are severely inhibited in their capacity to differentiate into mature osteoclasts in the presence of M-CSF and receptor activator of NF-κB (RANK) ligand. We also show that BMP noncanonical (MAPK) and canonical (SMAD) pathways are utilized at different stages of osteoclast differentiation. BMP2 induces p38 phosphorylation in pre-fusion osteoclasts and increases SMAD phosphorylation around osteoclast precursor fusion. Phosphorylation of MAPKs was decreased in differentiated BMMs from cKO animals. Treating BMMs with the SMAD inhibitor dorsomorphin confirms the requirement for the canonical pathway around the time of fusion. These results demonstrate the requirement for BMP signaling in osteoclasts for proper bone homeostasis and also explore the complex signaling mechanisms employed by BMP signaling during osteoclast differentiation. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00219258
Volume :
288
Issue :
52
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
93378021
Full Text :
https://doi.org/10.1074/jbc.M113.496950