RRC ID 52079
Author Ozeki N, Hase N, Hiyama T, Yamaguchi H, Kawai-Asano R, Nakata K, Mogi M.
Title MicroRNA-211 and autophagy-related gene 14 signaling regulate osteoblast-like cell differentiation of human induced pluripotent stem cells.
Journal Exp Cell Res
Abstract MicroRNAs (miRNAs) have been the subject of recent attention as key regulatory factors in cell differentiation. In the current study, to explore the early signaling cascade of osteogenic differentiation of human induced pluripotent stem (hiPS) cells, we investigated miR-211 regulation and autophagy-related gene (Atg) signaling in osteogenic differentiation. In addition to reciprocal strong induction of miR-211 expression in differentiated cells following osteogenic differentiation, we found abundant Argonaute 3 bound to miR-211. There were also dramatic increases in the mRNA and protein levels of Atg14 together with increases in the amount of autophagosomes as well as autophagic fluxes. While transfection of a miR-211 inhibitor abrogated the induction of Atg14, autophagy events, osteoblast differentiation markers, and induction of calcification were suppressed markedly. Treatment with small interfering RNAs against Atg14 also suppressed the osteogenic differentiation medium (ODM)-induced increase in osteogenic differentiation. The osteogenic phenotype was inhibited by chloroquine (an autophagy inhibitor), but increased after treatment with rapamycin (an autophagy inducer). Taken together with our previous findings, we have revealed a unique sequential cascade involving miR-211 and Atg14 in ODM-induced differentiation of hiPS cells into osteoblast-like cells at a relatively early stage.
Volume 352(1)
Pages 63-74
Published 2017-3-1
DOI 10.1016/j.yexcr.2017.01.018
PII S0014-4827(17)30029-0
PMID 28159471
MeSH Adaptor Proteins, Vesicular Transport / antagonists & inhibitors Adaptor Proteins, Vesicular Transport / genetics Adaptor Proteins, Vesicular Transport / metabolism* Autophagy* Autophagy-Related Proteins / antagonists & inhibitors Autophagy-Related Proteins / genetics Autophagy-Related Proteins / metabolism* Blotting, Western Cell Differentiation* Cells, Cultured Humans Induced Pluripotent Stem Cells / cytology* Induced Pluripotent Stem Cells / metabolism MicroRNAs / genetics* Osteoblasts / cytology* Osteoblasts / metabolism Osteogenesis / physiology RNA, Messenger / genetics RNA, Small Interfering / genetics Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction
IF 3.383
Times Cited 16
Resource
Human and Animal Cells 201B7(HPS0063)