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Forkhead box O1 (FoxO1) protein is crucial for defending physiological oxidative damage in bone. But whether FoxO1 is involved in the oxidative damage during osteoporosis is largely unknown. In this study, we found that FoxO1 protein accumulation was decreased in BMMSCs of ovariectomized mice. The decrease of FoxO1 resulted in the suppression of manganese superoxide dismutase (Sod2) and catalase (Cat) expression and accumulation of reactive oxygen species (ROS), inhibiting the osteogenic differentiation of BMMSCs. The decline of FoxO1 protein was caused by tumor necrosis factor-alpha (TNF-\u03b1) accumulated after estrogen deficiency. Mechanistically, TNF-\u03b1 activated NF-\u03baB pathway to promote microRNA-705 expression, which function as a repressor of FoxO1 through post-transcriptional regulation. Inhibition of NF-\u03baB pathway or knockdown of miR-705 largely prevented the decline of FoxO1-mediated antioxidant defense caused by TNF-\u03b1 and ameliorated the oxidative damage in osteoporotic BMMSCs. Moreover, the accumulated ROS further activated NF-\u03baB pathway with TNF-\u03b1, which formed a feed-forward loop to persistently inhibiting FoxO1 protein accumulation in BMMSCs. In conclusion, our study revealed that the decline of FoxO1 is an important etiology factor of osteoporosis and unclosed a novel mechanism of FoxO1 regulation by TNF-\u03b1. These findings suggested a close correlation between inflammation and oxidative stress in stem cell dysfunction during degenerative bone diseases.<\/jats:p>","DOI":"10.1002\/stem.2274","type":"journal-article","created":{"date-parts":[[2015,12,23]],"date-time":"2015-12-23T19:09:08Z","timestamp":1450897748000},"page":"1054-1067","source":"Crossref","is-referenced-by-count":118,"title":["TNF-\u03b1 Inhibits FoxO1 by Upregulating miR-705 to Aggravate Oxidative Damage in Bone Marrow-Derived Mesenchymal Stem Cells during Osteoporosis"],"prefix":"10.1093","volume":"34","author":[{"given":"Li","family":"Liao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Military Stomatology, Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China"},{"name":"Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China"},{"name":"State Key Laboratory of Military 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