title: Simulated microgravity inhibits osteogenic differentiation of mesenchymal stem cells through down regulating the transcriptional co-activator TAZ.
abstract: Microgravity induces observed bone loss in space flight or simulated experiments, while the mechanism underlying it is still obscure. Here, we utilized a clinostat to model simulated microgravity (SMG) and found that SMG obviously inhibited osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs). We detected that SMG dramatically inhibited the expression of the transcriptional coactivator with PDZ-binding motif (TAZ), which acts as a vital regulator of osteogenesis. Interestingly, we found that lysophosphatidic acid (LPA) could activate TAZ and retain osteogenic differentiation of BMSCs under SMG. Our data further demonstrated that depletion of TAZ by siRNA blocked the LPA-induced increase in osteogenic differentiation of BMSCs under SMG. Moreover, Y27632 (the Rock inhibitor) abrogated the activation of TAZ and the increased osteogenic differentiation induced by LPA. Taken together, we propose that microgravity inhibits osteogenic differentiation of BMSCs due to decreased TAZ expression and that LPA can efficiently reverse the reduced osteogenic differentiation via the Rock-TAZ pathway.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
authors.forename: Chuanchuan
authors.initials: C
authors.lastname: Lin
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address: song@cqu.edu.cn.
authors.forename: Guanbin
authors.initials: G
authors.lastname: Song
mesh_terms: D000217:Acyltransferases; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D004867:Equipment Design; D008246:Lysophospholipids / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014893:Weightlessness; D018474:Weightlessness Simulation / Q000295:instrumentation; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000217:Acyltransferases; C544439:Tafazzin protein, rat; D054460:rho-Associated Kinases; C032881:lysophosphatidic acid
keywords: LPA; Mesenchymal stem cells; Microgravity; Osteogenic differentiation; TAZ