Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells via depolymerizing F-actin to impede TAZ nuclear translocation

• DOI: 10.1038/srep30322
• Publication Date: 2016-07-22T10:21:37Z
• Authors: Zhe Chen; Qing Luo; Chuanchuan Lin; Dongdong Kuang; Guanbin Song
• Keywords: RUNX2

Abstract Microgravity induces observed bone loss in space flight and reduced osteogenesis of mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning the actin cytoskeleton induced by microgravity may cause inhibited BMSCs, but underlying mechanism remains obscure. In study, we demonstrated that cytoskeletal changes regulate nuclear aggregation transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for (BMSCs). Moreover, utilized a clinostat model simulated (SMG) SMG obviously depolymerized F-actin hindered TAZ translocation. Interestingly, stabilizing Jasplakinolide (Jasp) significantly rescued translocation recovered osteogenic differentiation BMSCs SMG, independently large tumor suppressor 1(LATS1, an upstream kinase TAZ). Furthermore, lysophosphatidic acid (LPA) also through F-actin-TAZ pathway. Taken together, propose inhibits impeding TAZ, provides novel connection between has important implications caused microgravity.