失重抑制骨形成的重要原因之一是引起成骨细胞氧化应激导致成骨分化下降，但作用机制不明。FOXO1在成骨细胞防御氧化应激中尤为重要，需β-catenin参与激活下游基因转录。申请者发现，细胞骨架交联因子MACF1参与成骨细胞抗氧化：模拟失重条件抑制MACF1表达、成骨细胞抗氧化和分化能力下降；MACF1影响β-catenin的表达及入核；MACF1低表达抑制FOXO1激活下游基因转录。因此提出：模拟失重条件下，MACF1可能通过β-catenin，调节FOXO1转录活性，影响细胞抗氧化，调控成骨细胞分化和骨形成。本项目拟研究：模拟失重对⑴骨形成，成骨细胞氧化应激和分化的影响；⑵MACF1与FOXO1表达，FOXO1与β-catenin相互作用和转录活性的影响。⑶MACF1高表达对模拟失重引起成骨细胞氧化应激抑制骨形成的挽救作用及机制。以期为防治空间失重性骨质流失提供理论基础和新靶点

The increased oxidative stress and decreased differentiation ability of osteoblast induced by weight loss is the main cause of weightlessness-induced bone loss. However, the mechanism is still unclear. FOXO1 antioxidant pathways is particularly important in signaling networks that regulate osteoblast differentiation, which requires β-catenin to initiate downstream gene transcription. Our team found that simulated weight loss conditions decreased MACF1 expression in osteoblasts, reduced the antioxidant, differentiation and mineralization capacity of osteoblast; MACF1 affecedt the expression of β-catenin and its nuclear translocation. Therefore, under the condition of simulated weightlessness, MACF1 may regulate FOXO1 pathway through β-catenin, affect the redox state of cells, regulate osteoblast differentiation and bone formation. This project intends to study (1) the change of cell oxidative stress, cell differentiation and bone formation under simulated weightlessness condition; (2) the impact of simulated weightlessness condition on the expression of MACF1 and FOXO1, and the interaction between FOXO1 and β-catenin, as well as the transcriptional activity of FOXO1/β-catenin. (3) If MACF1 over-expression could rescue the osteoblast oxidative stress and the inhibitory effect of bone formation by simulated weightlessness conditions. The results of this project will provide a theoretical basis for the clarification and protection of spatial bone loss.