| First Author | Cui M | Year | 2015 |
| Journal | Sci Rep | Volume | 5 |
| Pages | 16455 | PubMed ID | 26558437 |
| Mgi Jnum | J:251404 | Mgi Id | MGI:6101656 |
| Doi | 10.1038/srep16455 | Citation | Cui M, et al. (2015) OASIS modulates hypoxia pathway activity to regulate bone angiogenesis. Sci Rep 5:16455 |
| abstractText | OASIS/CREB3L1, an endoplasmic reticulum (ER)-resident transcription factor, plays important roles in osteoblast differentiation. In this study, we identified new crosstalk between OASIS and the hypoxia signaling pathway, which regulates vascularization during bone development. RT-PCR and real-time PCR analyses revealed significant decreases in the expression levels of hypoxia-inducible factor-1alpha (HIF-1alpha) target genes such as vascular endothelial growth factor A (VEGFA) in OASIS-deficient (Oasis(-/-)) mouse embryonic fibroblasts. In coimmunoprecipitation experiments, the N-terminal fragment of OASIS (OASIS-N; activated form of OASIS) bound to HIF-1alpha through the bZIP domain. Luciferase assays showed that OASIS-N promoted the transcription activities of a reporter gene via a hypoxia-response element (HRE). Furthermore, the expression levels of an angiogenic factor Vegfa was decreased in Oasis(-/-) osteoblasts. Immunostaining and metatarsal angiogenesis assay showed retarded vascularization in bone tissue of Oasis(-/-) mice. These results suggest that OASIS affects the expression of HIF-1alpha target genes through the protein interaction with HIF-1alpha, and that OASIS-HIF-1alpha complexes may play essential roles in angiogenesis during bone development. |
