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initiation and progression of osteoporosis. Although OS is closely associated with mitochondrial dysfunction, detailed mitochondrial mechanisms underlying OS-induced osteoblast apoptosis have not been thoroughly elucidated to date. In the present study, we found that mitochondrial abnormalities largely contributed to OS-induced osteoblast apoptosis, as evidenced by enhanced production of mitochondrial reactive oxygen species; considerable reduction in mitochondrial respiratory chain complex activity, mitochondrial membrane potential, and adenosine triphosphate production; abnormality in mitochondrial morphology; and alteration of mitochondrial dynamics. These mitochondrial abnormalities were primarily mediated by an imbalance in mitochondrial fusion and fission through a protein kinase B- (AKT-) glycogen synthase kinase 3<jats:italic>\u03b2-<\/jats:italic>(GSK3<jats:italic>\u03b2-<\/jats:italic>) optic atrophy 1- (OPA1-) dependent mechanism. Hydroxytyrosol (3,4-dihydroxyphenylethanol (HT)), an important compound in virgin olive oil, significantly prevented OS-induced osteoblast apoptosis. Specifically, HT inhibited OS-induced mitochondrial dysfunction by decreasing OPA1 cleavage and by increasing AKT and GSK3<jats:italic>\u03b2<\/jats:italic>phosphorylation. Together, our results indicate that the AKT-GSK3<jats:italic>\u03b2<\/jats:italic>signaling pathway regulates mitochondrial dysfunction-associated OPA1 cleavage, which may contribute to OS-induced osteoblast apoptosis. Moreover, our results suggest that HT could be an effective nutrient for preventing osteoporosis development.<\/jats:p>","DOI":"10.1155\/2019\/4101738","type":"journal-article","created":{"date-parts":[[2019,6,2]],"date-time":"2019-06-02T23:32:27Z","timestamp":1559518347000},"page":"1-20","source":"Crossref","is-referenced-by-count":56,"title":["AKT-GSK3<i>\u03b2<\/i>Signaling Pathway Regulates Mitochondrial Dysfunction-Associated OPA1 Cleavage Contributing to Osteoblast Apoptosis: Preventative Effects of Hydroxytyrosol"],"prefix":"10.1155","volume":"2019","author":[{"given":"W. 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