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Bone marrow mesenchymal stem cells (BMSCs) can differentiate into bone\u2010forming osteoblasts, and play an important role in maintaining homeostasis of bone metabolism, thus being a potential therapeutic target for osteoporosis. Although the phytochemical alpinetin (APT) has been reported to possess a variety of pharmacological activities, it is still unclear whether APT can influence the osteogenic differentiation of on BMSCs and if it can improve osteoporosis. In this study, we found that APT treatment was able to enhance osteogenic differentiation levels of human BMSCs in vitro and mouse ones in vivo as revealed by multiple osteogenic markers including increased alkaline phosphatase activity and osteocalcin expression. Mechanistically, the protein kinase A (PKA)\/mTOR\/ULK1 signaling was involved in the action of APT to enhance the osteogenic differentiation of BMSCs. In addition, oral administration of APT significantly mitigated the bone loss in a dexamethasone\u2010induced mouse model of osteoporosis through strengthening PKA signaling and autophagy. Altogether, these data demonstrate that APT promotes osteogenic differentiation in BMSCs by augmenting the PKA\/mTOR\/ULK1 autophagy signaling, highlighting its potential therapeutic application for treating osteoporotic diseases.<\/jats:p>","DOI":"10.1002\/ptr.7610","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T01:35:57Z","timestamp":1663205757000},"page":"252-270","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in <scp>BMSCs<\/scp> by triggering autophagy via <scp>PKA<\/scp>\/<scp>mTOR<\/scp>\/<scp>ULK1<\/scp> signaling"],"prefix":"10.1002","volume":"37","author":[{"given":"Chenying","family":"Zeng","sequence":"first","affiliation":[{"name":"Center for Biotherapy Eighth Affiliated Hospital of Sun Yat\u2010sen University  Shenzhen People's Republic of 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