| dc.contributor.author | Carcamo-Orive, I | en_US |
| dc.contributor.author | Gaztelumendi, A | en_US |
| dc.contributor.author | Delgado, J | en_US |
| dc.contributor.author | Tejados, N | en_US |
| dc.contributor.author | Dorronsoro, A | en_US |
| dc.contributor.author | Fernandez-Rueda, J | en_US |
| dc.contributor.author | Pennington, DJ | en_US |
| dc.contributor.author | Trigueros, C | en_US |
| dc.date.accessioned | 2013-01-29T11:22:37Z | |
| dc.date.issued | 2010-10 | en_US |
| dc.identifier.issn | 0884-0431 | en_US |
| dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/3298 | |
| dc.format.extent | 2115 - 2125 | en_US |
| dc.relation.ispartof | J BONE MINER RES | en_US |
| dc.rights | Although marrow adipocytes and osteoblasts derive from a common bone marrow stromal cells (BMSCs), the mechanisms that underlie osteoporosis‐associated bone loss and marrow adipogenesis during prolonged steroid treatment are unclear. We show in human BMSCs (hBMSCs) that glucocorticoid receptor (GR) signaling in response to high concentrations of glucocorticoid (GC) supports adipogenesis but inhibits osteogenesis by reducing c‐Jun expression and hBMSC proliferation. Conversely, significantly lower concentrations of GC, which permit hBMSC proliferation, are necessary for normal bone mineralization. In contrast, platelet‐derived growth factor (PDGF) signaling increases both JNK/c‐Jun activity and hBMSC expansion, favoring osteogenic differentiation instead of adipogenesis. Indeed, PDGF antagonizes the proadipogenic qualities of GC/GR signaling. Thus our results reveal a novel c‐Jun‐centered regulatory network of signaling pathways in differentiating hBMSCs that controls the proliferation‐dependent balance between osteogenesis and adipogenesis. | |
| dc.subject | OSTEOBLASTS AND STEM CELLS | en_US |
| dc.subject | BONE | en_US |
| dc.subject | ADIPOSE | en_US |
| dc.subject | CORTICOSTEROID OSTEOPOROSIS | en_US |
| dc.subject | MESENCHYMAL STEM-CELLS | en_US |
| dc.subject | JUN GENE-EXPRESSION | en_US |
| dc.subject | C-JUN | en_US |
| dc.subject | ADIPOCYTIC DIFFERENTIATION | en_US |
| dc.subject | COORDINATE REGULATION | en_US |
| dc.subject | STEROID-HORMONES | en_US |
| dc.subject | GROWTH-FACTOR | en_US |
| dc.subject | OSTEOPOROSIS | en_US |
| dc.subject | MODULATION | en_US |
| dc.subject | MECHANISMS | en_US |
| dc.title | Regulation of Human Bone Marrow Stromal Cell Proliferation and Differentiation Capacity by Glucocorticoid Receptor and AP-1 Crosstalk | en_US |
| dc.type | Article | |
| dc.rights.holder | Copyright © 2010 American Society for Bone and Mineral Research | |
| dc.identifier.doi | 10.1002/jbmr.120 | en_US |
| pubs.issue | 10 | en_US |
| pubs.notes | Not known | en_US |
| pubs.volume | 25 | en_US |
