| First Author | Roforth MM | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 440 |
| Issue | 4 | Pages | 768-73 |
| PubMed ID | 24125721 | Mgi Jnum | J:211527 |
| Mgi Id | MGI:5575617 | Doi | 10.1016/j.bbrc.2013.10.006 |
| Citation | Roforth MM, et al. (2013) Identification of Rorbeta targets in cultured osteoblasts and in human bone. Biochem Biophys Res Commun 440(4):768-73 |
| abstractText | Control of osteoblastic bone formation involves the cumulative action of numerous transcription factors, including both activating and repressive functions that are important during specific stages of differentiation. The nuclear receptor retinoic acid receptor-related orphan receptor beta (Rorbeta) has been recently shown to suppress the osteogenic phenotype in cultured osteoblasts, and is highly upregulated in bone marrow-derived osteogenic precursors isolated from aged osteoporotic mice, suggesting Rorbeta is an important regulator of osteoblast function. However the specific gene expression patterns elicited by Rorbeta are unknown. Using microarray analysis, we identified 281 genes regulated by Rorbeta in an MC3T3-E1 mouse osteoblast cell model (MC3T3-Rorbeta-GFP). Pathway analysis revealed alterations in genes involved in MAPK signaling, genes involved in extracellular matrix (ECM) regulation, and cytokine-receptor interactions. Whereas the identified Rorbeta-regulated ECM genes normally decline during osteoblastic differentiation, they were highly upregulated in this non-mineralizing MC3T3-Rorbeta-GFP model system, suggesting that Rorbeta may exert its anti-osteogenic effects through ECM disruption. Consistent with these in vitro findings, the expression of both RORbeta and a subset of RORbeta-regulated genes were increased in bone biopsies from postmenopausal women (73+/-7 years old) compared to premenopausal women (30+/-5 years old), suggesting a role for RORbeta in human age-related bone loss. Collectively, these data demonstrate that Rorbeta regulates known osteogenic pathways, and may represent a novel therapeutic target for age-associated bone loss. |
