Details

Autor(en) / Beteiligte

• Grassi, Francesco
• Tell, Gianluca
• Robbie-Ryan, Michaela
• Gao, Yuhao
• Terauchi, Masakazu
• Yang, Xiaoying
• Romanello, Milena
• Jones, Dean P
• Weitzmann, M. Neale
• Pacifici, Roberto

Titel

Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2007-09, Vol.104 (38), p.15087-15092

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2007

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Increased production of tumor necrosis factor α (TNF) in the bone marrow (BM) in response to both oxidative stress and T cell activation contributes to the bone loss induced by estrogen deficiency, but it is presently unknown whether oxidative stress causes bone loss through T cells. Here we show that ovariectomy causes an accumulation in the BM of reactive oxygen species, which leads to increased production of TNF by activated T cells through up-regulation of the costimulatory molecule CD80 on dendritic cells. Accordingly, bone loss is prevented by treatment of ovariectomized mice with either antioxidants or CTLA4-Ig, an inhibitor of the CD80/CD28 pathway. In summary, reactive oxygen species accumulation in the BM is an upstream consequence of ovariectomy that leads to bone loss by activating T cells through enhanced activity of BM dendritic cells, and these findings suggest that the CD80/CD28 pathway may represent a therapeutic target for postmenopausal bone loss.