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In this study, we engineered a functional three-dimensional (3D) in vitro skeletal muscle model to investigate steroid myopathy. By subjecting our bioengineered muscle tissues to dexamethasone treatment, we reproduced the molecular and functional aspects of this disease. Dexamethasone caused a substantial reduction in muscle force, myotube diameter and induced fatigue. We observed nuclear translocation of the glucocorticoid receptor (GCR) and activation of the ubiquitin\u2013proteasome system within our model, suggesting their coordinated role in muscle atrophy. We then examined the therapeutic potential of taurine in our 3D model for steroid myopathy. Our findings revealed an upregulation of phosphorylated AKT by taurine, effectively countering the hyperactivation of the ubiquitin\u2013proteasomal pathway. Importantly, we demonstrate that discontinuing corticosteroid treatment was insufficient to restore muscle mass and function. Taurine treatment, when administered concurrently with corticosteroids, notably enhanced contractile strength and protein turnover by upregulating the AKT\u2013mTOR axis. Our model not only identifies a promising therapeutic target, but also suggests combinatorial treatment that may benefit individuals undergoing corticosteroid treatment or those diagnosed with adrenal tumors.<\/jats:p>","DOI":"10.1242\/dmm.050540","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T07:17:55Z","timestamp":1713943075000},"source":"Crossref","is-referenced-by-count":12,"title":["Taurine activates the AKT\u2013mTOR axis to restore muscle mass and contractile strength in human 3D <i>in vitro<\/i> models of steroid myopathy"],"prefix":"10.1242","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0439-628X","authenticated-orcid":false,"given":"Sheeza","family":"Mughal","sequence":"first","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST) 1 , C\/Baldiri Reixac 10-12, E08028 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8191-1401","authenticated-orcid":false,"given":"Maria","family":"Sabater-Arcis","sequence":"additional","affiliation":[{"name":"University Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia 2 , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"},{"name":"Incliva Health Research Institute 3 Translational Genomics Group , , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"},{"name":"Joint Unit Incliva- CIPF 4 , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1596-047X","authenticated-orcid":false,"given":"Ruben","family":"Artero","sequence":"additional","affiliation":[{"name":"University Institute for Biotechnology and Biomedicine (BIOTECMED), University of Valencia 2 , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"},{"name":"Incliva Health Research Institute 3 Translational Genomics Group , , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"},{"name":"Joint Unit Incliva- CIPF 4 , Dr Moliner 50, E46100 Burjassot, Valencia , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-8013","authenticated-orcid":false,"given":"Javier","family":"Ram\u00f3n-Azc\u00f3n","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST) 1 , C\/Baldiri Reixac 10-12, E08028 Barcelona , Spain"},{"name":"Instituci\u00f3 Catalana de Reserca i Estudis Avan\u00e7ats (ICREA) 5 , Passeig de Llu\u00eds Companys, 23, E08010 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-6082","authenticated-orcid":false,"given":"Juan M.","family":"Fern\u00e1ndez-Costa","sequence":"additional","affiliation":[{"name":"Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST) 1 , C\/Baldiri Reixac 10-12, E08028 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"2024042407174294100_DMM050540C1","doi-asserted-by":"publisher","first-page":"4759","DOI":"10.1113\/jphysiol.2011.212845","article-title":"Muscle sparing in muscle RING finger 1 null mice: response to synthetic glucocorticoids","volume":"589","author":"Baehr","year":"2011","journal-title":"J. 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