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Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC\u2010ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC\u2010ONFH. For in\u00a0vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC\u2010induced autophagy levels and osteogenic activity dysfunction. For in\u00a0vivo experiments, a rat model of GC\u2010ONFH was used for evaluating the therapeutic effect of oral lithium on GC\u2010ONFH and underlying mechanism. Findings demonstrated that GC over\u2010activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over\u2010activated autophagy of GC\u2010treated osteoblasts through PI3K\/AKT\/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC\u2010ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K\/AKT\/mTOR signalling pathway. In conclusion, lithium can restrain over\u2010activated autophagy by activating PI3K\/AKT\/mTOR signalling pathway and up\u2010regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC\u2010ONFH. Lithium may be a promising therapeutic agent for GC\u2010ONFH. However, the role of autophagy in the pathogenesis of GC\u2010ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC\u2010ONFH, and the efficacy of lithium in the treatment of GC\u2010ONFH and its underlying mechanisms.<\/jats:p>","DOI":"10.1111\/jcmm.18385","type":"journal-article","created":{"date-parts":[[2024,5,27]],"date-time":"2024-05-27T14:40:27Z","timestamp":1716820827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lithium prevents glucocorticoid\u2010induced osteonecrosis of the femoral head by regulating autophagy"],"prefix":"10.1111","volume":"28","author":[{"given":"Qiuru","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery, West China Hospital Sichuan University  Chengdu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhouyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, West China Hospital Sichuan 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