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Chronic oxidative stress, induced by excessive reactive oxygen species (ROS) associated with aging, is a critical factor underlying the development of osteoporosis in elderly individuals and a diminished capacity for bone formation and osteogenic differentiation. However, the mechanism underlying age\u2010related osteoporosis remains unclear. MACF1 (microtubule actin crosslinking factor 1) is an essential factor that regulates bone formation and development, and exhibits reduced expression as humans age. In this study, we used MACF1 conditional knockout (MACF1\u2010cKO) mice as a premature aging model and found that MACF1\u2010cKO mice exhibited chronic oxidative stress. Moreover, the expression level, nuclear translocation, and transcriptional activity of FoxO1 were promoted in MACF1 deficient osteoblastic cells. In addition, the binding of FoxO1 to \u03b2\u2010catenin was enhanced, increasing the transcriptional activity of the FoxO1\/\u03b2\u2010catenin pathway in MACF1 deficient osteoblastic cells. The enhanced FoxO1\/\u03b2\u2010catenin pathway competitively weakens the binding of \u03b2\u2010catenin to TCF7 and decreases the activity of the TCF7\/\u03b2\u2010catenin pathway. Our study showed that FoxO1 responded to chronic oxidative stress induced by MACF1 deficiency to determine \u03b2\u2010catenin fate and regulate osteoblast differentiation during senile osteoporosis.<\/jats:p>","DOI":"10.1111\/acel.70306","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T14:31:06Z","timestamp":1765290666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>FoxO1<\/scp>\n                    Responses to Chronic Oxidative Stress to Participate in Age\u2010Related Osteoporosis by Depriving \u03b2\u2010Catenin From\n                    <scp>TCF7<\/scp>"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3657-3129","authenticated-orcid":false,"given":"Peihong","family":"Su","sequence":"first","affiliation":[{"name":"Lab for Bone Metabolism, Xi'an Key Laboratory of Special Medicine and Health Engineering, Key Lab for Space 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