Back to Search
Start Over
Estrogen-related receptor α regulates osteoblast differentiation via Wnt/β-catenin signaling
- Source :
- Journal of Molecular Endocrinology. 48:177-191
- Publication Year :
- 2012
- Publisher :
- Bioscientifica, 2012.
-
Abstract
- Based on its homology to the estrogen receptor and its roles in osteoblast and chondrocyte differentiation, the orphan nuclear receptor estrogen-related receptor α (ERRα (ESRRA)) is an intriguing therapeutic target for osteoporosis and other bone diseases. The objective of this study was to better characterize the molecular mechanisms by which ERRα modulates osteoblastogenesis. Experiments from multiple systems demonstrated that ERRα modulates Wnt signaling, a crucial pathway for proper regulation of bone development. This was validated using a Wnt-luciferase reporter, where ERRα showed co-activator-dependent (peroxisome proliferator-activated receptor gamma co-activator 1α, PGC-1α) stimulatory effects. Interestingly, knockdown ofERRαexpression also enhanced WNT signaling. In combination, these data indicated that ERRα could serve to either activate or repress Wnt signaling depending on the presence or absence of its co-activator PGC-1α. The observed Wnt pathway modulation was cell intrinsic and did not alter β-catenin nuclear translocation but was dependent on DNA binding of ERRα. We also found that expression of active ERRα correlated with Wnt pathway effects on osteoblastic differentiation in two cell types, consistent with a role for ERRα in modulating the Wnt pathway. In conclusion, this work identifies ERRα, in conjunction with co-activators such as PGC-1α, as a new regulator of the Wnt-signaling pathway during osteoblast differentiation, through a cell-intrinsic mechanism not affecting β-catenin nuclear translocation.
- Subjects :
- Active Transport, Cell Nucleus
Regulator
Estrogen receptor
Biology
Mice
Estrogen-related receptor
Endocrinology
Genes, Reporter
Osteogenesis
medicine
Animals
Humans
Receptor
Wnt Signaling Pathway
Molecular Biology
Cells, Cultured
beta Catenin
Gene knockdown
Osteoblasts
Skull
Wnt signaling pathway
Cell Differentiation
Mesenchymal Stem Cells
Osteoblast
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Cell biology
Wnt Proteins
medicine.anatomical_structure
Receptors, Estrogen
Nuclear receptor
Gene Knockdown Techniques
Trans-Activators
Transcription Factors
Subjects
Details
- ISSN :
- 14796813 and 09525041
- Volume :
- 48
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Endocrinology
- Accession number :
- edsair.doi.dedup.....cb07675aab1e4cb87d02c81bb6fe3c61
- Full Text :
- https://doi.org/10.1530/jme-11-0140