Abstract
Recent studies have confirmed that microRNAs and lncRNAs can affect bone cell differentiation and bone formation. In this study, miR-139-3p was upregulated in the femurs of hindlimb unloading mice and MC3T3-E1 cells under simulated microgravity; this effect was related to osteoblast differentiation and apoptosis. Silencing miR-139-3p attenuated the suppression of differentiation and the promotion of MC3T3-E1 cell apoptosis induced by simulated microgravity. ELK1 is a target of miR-139-3p and is essential for miR-139-3p to regulate osteoblast differentiation and apoptosis. An osteoblast differentiation-related lncRNA that could interact with miR-139-3p (lncRNA ODSM) was identified in MC3T3-E1 cells under simulated microgravity. Further investigations demonstrated that lncRNA ODSM could promote MC3T3-E1 cell differentiation. Therefore, this research was the first to reveal the critical role of the lncRNA ODSM/miR-139-3p/ELK1 pathway in osteoblasts, and these findings suggest the potential value of miR-139-3p in osteoporosis diagnosis and therapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics*
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Base Sequence
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Caspase 3 / genetics
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Caspase 3 / metabolism
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Cell Differentiation
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Cell Line
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Femur / metabolism
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Femur / pathology
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Gene Expression Regulation
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Hindlimb Suspension
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Male
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Mechanotransduction, Cellular / genetics
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Mice
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Mice, Inbred C57BL
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Oligoribonucleotides / genetics
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Oligoribonucleotides / metabolism
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Osteoblasts / metabolism*
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Osteoblasts / pathology
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Osteogenesis / genetics*
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Primary Cell Culture
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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RNA, Long Noncoding / genetics*
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RNA, Long Noncoding / metabolism
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Weightlessness Simulation
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism
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ets-Domain Protein Elk-1 / genetics*
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ets-Domain Protein Elk-1 / metabolism
Substances
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Bax protein, mouse
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Elk1 protein, mouse
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MIRN139 microRNA, mouse
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MicroRNAs
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Oligoribonucleotides
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Proto-Oncogene Proteins c-bcl-2
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RNA, Long Noncoding
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bcl-2-Associated X Protein
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ets-Domain Protein Elk-1
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Bcl2 protein, mouse
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Casp3 protein, mouse
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Caspase 3