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In cases of prolonged treatment, glucocorticoids promote the loss and inactivation of the differentiational function of bone marrow mesenchymal stromal cells (BMSCs), risking the development of skeletal system diseases such as osteoporosis. This study reports for the first time the protective effect of the antimalarial artemisinin against glucocorticoid\u2010induced insults on primary cultured rat BMSCs. At relatively low concentrations, artemisinin treatment improved BMSC survival by promoting a decline of reactive oxygen species (ROS) production that correlated with the decrease of caspase\u20103 activation, LDH release, mitochondrial membrane potential (<jats:italic>\u0394\u03c8<\/jats:italic>m) loss, and apoptosis induced by dexamethasone (DEXA). In addition, artemisinin improved the osteogenic differentiation of DEXA\u2010damaged cells. DEXA inhibited extracellular\u2010signal\u2010regulated kinase 1\/2 (ERK1\/2) and cAMP response element binding protein (CREB) phosphorylation, and artemisinin treatment promoted their activation in a concentration\u2010dependent manner. PD98059, the specific inhibitor of the ERK1\/2 pathway, blocked ERK1\/2 phosphorylation and artemisinin protection. Similarly, siCREB attenuated the protective effect of artemisinin, strongly suggesting the involvement of the ERK1\/2\u2010CREB pathway in the protective action of artemisinin against DEXA\u2010induced damage in BMSCs. In addition, we found that the expression of antiapoptotic protein B\u2010cell lymphoma 2 protein (BCL\u20102) was also upregulated by artemisinin. These studies demonstrate the therapeutic potential of artemisinin in the survival improvement of BMSCs exposed to glucocorticoid\u2010induced apoptosis and suggest that artemisinin\u2010mediated protection may occur via the activation of ERK1\/2\u2010CREB signaling pathway.<\/jats:p>","DOI":"10.1155\/2021\/5574932","type":"journal-article","created":{"date-parts":[[2021,9,18]],"date-time":"2021-09-18T01:35:06Z","timestamp":1631928906000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Artemisinin Reverses Glucocorticoid\u2010Induced Injury in Bone Marrow\u2010Derived Mesenchymal Stem Cells through Regulation of ERK1\/2\u2010CREB Signaling 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