| First Author | Gao Y | Year | 2004 |
| Journal | Proc Natl Acad Sci U S A | Volume | 101 |
| Issue | 47 | Pages | 16618-23 |
| PubMed ID | 15531637 | Mgi Jnum | J:94469 |
| Mgi Id | MGI:3512846 | Doi | 10.1073/pnas.0404888101 |
| Citation | Gao Y, et al. (2004) Estrogen prevents bone loss through transforming growth factor beta signaling in T cells. Proc Natl Acad Sci U S A 101(47):16618-23 |
| abstractText | Estrogen (E) deficiency leads to an expansion of the pool of tumor necrosis factor (TNF)-producing T cells through an IFN-gamma-dependent pathway that results in increased levels of the osteoclastogenic cytokine TNF in the bone marrow. Disregulated IFN-gamma production is instrumental for the bone loss induced by ovariectomy (ovx), but the responsible mechanism is unknown. We now show that mice with T cell-specific blockade of type beta transforming growth factor (TGFbeta) signaling are completely insensitive to the bone-sparing effect of E. This phenotype results from a failure of E to repress IFN-gamma production, which, in turn, leads to increased T cell activation and T cell TNF production. Furthermore, ovx blunts TGFbeta levels in the bone marrow, and overexpression of TGFbeta in vivo prevents ovx-induced bone loss. These findings demonstrate that E prevents bone loss through a TGFbeta-dependent mechanism, and that TGFbeta signaling in T cells preserves bone homeostasis by blunting T cell activation. Thus, stimulation of TGFbeta production in the bone marrow is a critical 'upstream' mechanism by which E prevents bone loss, and enhancement of TGFbeta levels in vivo may constitute a previously undescribed therapeutic approach for preventing bone loss. |
