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Bone Morphogenetic Proteins Signal Via SMAD and Mitogenactivated Protein (MAP) Kinase Pathways at Distinct Times during Osteoclastogenesis.
- 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]
- Subjects :
- *PROTEINS
*BONE cells
*BONE marrow
*IMMUNE system
*PHYSIOLOGICAL control systems
Subjects
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