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Posttranscriptional Interaction Between miR‐450a‐5p and miR‐28‐5p and STAT1 mRNA Triggers Osteoblastic Differentiation of Human Mesenchymal Stem Cells
Journal of cellular biochemistry, 2017-11, Vol.118 (11), p.4045-4062
Dernowsek, Janaína A.
Pereira, Milena C.
Fornari, Thaís A.
Macedo, Claudia
Assis, Amanda F.
Donate, Paula B.
Bombonato‐Prado, Karina F.
Passos‐Bueno, Maria Rita
Passos, Geraldo A.
2017
Volltextzugriff (PDF)
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Autor(en) / Beteiligte
Dernowsek, Janaína A.
Pereira, Milena C.
Fornari, Thaís A.
Macedo, Claudia
Assis, Amanda F.
Donate, Paula B.
Bombonato‐Prado, Karina F.
Passos‐Bueno, Maria Rita
Passos, Geraldo A.
Titel
Posttranscriptional Interaction Between miR‐450a‐5p and miR‐28‐5p and STAT1 mRNA Triggers Osteoblastic Differentiation of Human Mesenchymal Stem Cells
Ist Teil von
Journal of cellular biochemistry, 2017-11, Vol.118 (11), p.4045-4062
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2017
Quelle
Wiley Online Library All Journals
Beschreibungen/Notizen
ABSTRACT We demonstrate that the interaction between miR‐450a‐5p and miR‐28‐5p and signal transducer and activator of transcription 1 (STAT1) mRNA correlates with the osteoblastic differentiation of mesenchymal stem cells from human exfoliated deciduous teeth (shed cells). STAT1 negatively regulates runx‐related transcription factor 2 (RUNX2), which is an essential transcription factor in this process. However, the elements that trigger osteoblastic differentiation and therefore pause the inhibitory effect of STAT1 need investigation. Usually, STAT1 can be posttranscriptionally regulated by miRNAs. To test this, we used an in vitro model system in which shed cells were chemically induced toward osteoblastic differentiation and temporally analyzed, comparing undifferentiated cells with their counterparts in the early (2 days) or late (7 or 21 days) periods of induction. The definition of the entire functional genome expression signature demonstrated that the transcriptional activity of a large set of mRNAs and miRNAs changes during this process. Interestingly, STAT1 and RUNX2 mRNAs feature contrasting expression levels during the course of differentiation. While undifferentiated or early differentiating cells express high levels of STAT1 mRNA, which was gradually downregulated, RUNX2 mRNA was upregulated toward differentiation. The reconstruction of miRNA‐mRNA interaction networks allowed the identification of six miRNAs (miR‐17‐3p, miR‐28‐5p, miR‐29b, miR‐29c‐5p, miR‐145‐3p, and miR‐450a‐5p), and we predicted their respective targets, from which we focused on miR‐450a‐5p and miR‐28‐5p STAT1 mRNA interactions, whose intracellular occurrence was validated through the luciferase assay. Transfections of undifferentiated shed cells with miR‐450a‐5p or miR‐28‐5p mimics or with miR‐450a‐5p or miR‐28‐5p antagonists demonstrated that these miRNAs might play a role as posttranscriptional controllers of STAT1 mRNA during osteoblastic differentiation. J. Cell. Biochem. 118: 4045–4062, 2017. © 2017 Wiley Periodicals, Inc. (1) STAT1 and RUNX2 mRNAs feature contrasting expression levels during the course of osteoblastic differentiation of mesenchymal stem cells. (2) miRNA‐450a‐5p and miRNA‐28‐5p interacts with STAT1 mRNA during osteoblastic differentiation.
Sprache
Englisch
Identifikatoren
ISSN: 0730-2312
eISSN: 1097-4644
DOI: 10.1002/jcb.26060
Titel-ID: cdi_proquest_miscellaneous_1888679481
Format
–
Schlagworte
Antagonists
,
Biocompatibility
,
Biomedical materials
,
Cbfa-1 protein
,
Cell Differentiation
,
Child, Preschool
,
Differentiation (biology)
,
Gene expression
,
Genomes
,
Humans
,
In vitro methods and tests
,
Male
,
Mesenchymal stem cells
,
Mesenchymal Stromal Cells - cytology
,
Mesenchymal Stromal Cells - metabolism
,
Mesenchyme
,
microRNA ANTAGONIST
,
microRNA MIMIC
,
MicroRNAs - genetics
,
MicroRNAs - metabolism
,
miRNA
,
miR‐450a‐5p
,
OSTEOBLASTIC DIFFERENTIATION
,
Osteoblastogenesis
,
Osteoblasts
,
Osteoblasts - cytology
,
Osteoblasts - metabolism
,
Post-transcription
,
POSTTRANSCRIPTIONAL CONTROL
,
RNA, Messenger - metabolism
,
RUNX2
,
STAT1
,
Stat1 protein
,
STAT1 Transcription Factor - genetics
,
STAT1 Transcription Factor - metabolism
,
Stem cells
,
Teeth
,
Transcription factors
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