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Recently, aberrant expression of Runx2 has been found in OS, thereby contributing to the development, and progression of OS. However, the upstream signaling molecules that regulate its expression in OS remain largely unknown. In the present study, we first confirmed that the inhibition of HSP90 with 17\u2010AAG caused significant apoptosis of OS cells via a caspase\u20103\u2010dependent mechanism, and that inhibition or knockdown of HSP90 by 17\u2010AAG or siRNAs significantly suppressed mRNA and protein expression of Runx2. Furthermore, we provided evidence that Runx2 was transcriptionally regulated by HSP90 when using MG132 and CHX chase assay. We also demonstrated that \u03b2\u2010catenin was overexpressed in OS tissue, and that knockdown of \u03b2\u2010catenin induced pronounced apoptosis of OS cells in the presence or absence of 17\u2010AAG. Interestingly, this phenomenon was accompanied with a significant reduction of Runx2 and Cyclin D1 expression, indicating an essential role of Runx2\/Cyclin D1 in 17\u2010AAG\u2010induced cells apoptosis. Moreover, we demonstrated that the apoptosis of OS cells induced by 17\u2010AAG did require the involvement of the AKT\/GSK\u20103\u03b2\/\u03b2\u2010catenin signaling pathway by using pharmacological inhibitor GSK\u20103\u03b2 (LiCl) or siGSK\u20103\u03b2. Our findings reveal a novel mechanism that Runx2 is transcriptionally regulated by HSP90 via the AKT\/GSK\u20103\u03b2\/\u03b2\u2010catenin signaling pathway, and by which leads to apoptosis of OS cells.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.26260","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T11:22:42Z","timestamp":1499340162000},"page":"948-959","source":"Crossref","is-referenced-by-count":24,"title":["Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT\/GSK\u20103\u03b2\/\u03b2\u2010catenin signaling"],"prefix":"10.1002","volume":"119","author":[{"given":"Gui\u2010Hong","family":"Liang","sequence":"first","affiliation":[{"name":"The Third Affiliated Hospital Guangzhou University of Chinese Medicine Guangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Orthopedic Diseases and Center for Joint 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