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

Microgravity induces observed bone loss in space flight, and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the...

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Bibliographic Details
Published in:	Scientific reports 2016-07, Vol.6 (1), p.30322-30322, Article 30322
Main Authors:	Chen, Zhe, Luo, Qing, Lin, Chuanchuan, Kuang, Dongdong, Song, Guanbin
Format:	Article
Language:	eng
Subjects:	Actin Cytoskeleton - metabolism Actins - metabolism Active Transport, Cell Nucleus Amino Acid Motifs Animals Apoptosis Cell Differentiation Cell Survival Depsipeptides - pharmacology Flow Cytometry Intracellular Signaling Peptides and Proteins - metabolism Lysophospholipids - pharmacology Mesenchymal Stromal Cells - cytology Osteogenesis - physiology Rats Rats, Sprague-Dawley Signal Transduction Transcription Factors - metabolism Weightlessness Simulation
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Summary:	Microgravity induces observed bone loss in space flight, and reduced osteogenesis of bone mesenchymal stem cells (BMSCs) partly contributes to this phenomenon. Abnormal regulation or functioning of the actin cytoskeleton induced by microgravity may cause the inhibited osteogenesis of BMSCs, but the underlying mechanism remains obscure. In this study, we demonstrated that actin cytoskeletal changes regulate nuclear aggregation of the transcriptional coactivator with PDZ-binding motif (TAZ), which is indispensable for osteogenesis of bone mesenchymal stem cells (BMSCs). Moreover, we utilized a clinostat to model simulated microgravity (SMG) and demonstrated that SMG obviously depolymerized F-actin and hindered TAZ nuclear translocation. Interestingly, stabilizing the actin cytoskeleton induced by Jasplakinolide (Jasp) significantly rescued TAZ nuclear translocation and recovered the osteogenic differentiation of BMSCs in SMG, independently of large tumor suppressor 1(LATS1, an upstream kinase of TAZ). Furthermore, lysophosphatidic acid (LPA) also significantly recovered the osteogenic differentiation of BMSCs in SMG through the F-actin-TAZ pathway. Taken together, we propose that the depolymerized actin cytoskeleton inhibits osteogenic differentiation of BMSCs through impeding nuclear aggregation of TAZ, which provides a novel connection between F-actin cytoskeleton and osteogenesis of BMSCs and has important implications in bone loss caused by microgravity.
ISSN:	2045-2322 2045-2322