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Adipose\u2010derived stem cells (ASCs) have garnered attention in the field of bone renewal; the mechanisms leading to decreased osteogenesis within a diabetic environment are not fully understood. This study explores the effects\/molecular pathways of AGEs on the osteogenesis of ASCs both in vitro and in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A DOP mouse model was used, and ASCs were extracted from the inguinal fat of C57BL\/6 mice. ASCs were cultivated in an osteogenic differentiation medium and were exposed to AGEs, Torin1 (an autophagy activator), or ibandronate (IBAN), a PI3K\/Akt\/mTOR signalling inhibitor. Osteogenesis and autophagy activity were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>The expression of osteogenic markers, OPN and RUNX2, was decreased, ALP activities were impaired, and the formation of mineralised nodules was reduced in ASCs treated with AGEs. Additionally, the autophagic flux was blocked, and there was an increase in PI3K\/Akt\/mTOR signalling markers. After treatment with Torin1, the osteogenesis of ASCs in a diabetic microenvironment was restored by activating autophagy. Moreover, in the AGEs and DOP model, treatment with IBAN up\u2010regulated autophagy and rescued the impaired osteogenesis of ASCs in diabetic microenvironment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and implications<\/jats:title><jats:p>AGEs decreased the osteogenesis of ASCs by activating PI3K\/Akt\/mTOR signalling cascade and blocking autophagic flux. Autophagy induced by blocking the PI3K\/Akt\/mTOR signalling cascade could rescue the negative influences of ASCs in diabetic environment and provide a potential therapeutic strategy for bone renewal in individuals with DOP.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70016","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T02:07:22Z","timestamp":1743732442000},"page":"3522-3538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Activation of autophagy mediated by PI3K\/Akt\/mTOR signalling cascade alleviates impaired adipose\u2010derived stem cell osteogenesis in a diabetic microenvironment"],"prefix":"10.1111","volume":"182","author":[{"given":"Fangzhi","family":"Lou","sequence":"first","affiliation":[{"name":"Department of Oral Implantology, The Affiliated Stomatological Hospital Southwest Medical University  Luzhou 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