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miRNA‐mediated crosstalk between Wnt3a and TGFβ3 in osteoblast differentiation
Author(s) -
Fushimi Shigeko,
Nohno Tsutomu,
Nishimatsu Shinichiro,
Katase Naoki,
Terada Kumiko,
Katsuyama Midori,
Demura Masashi,
Saijoh Kiyofumi,
Nagatsuka Hitoshi,
Katsuyama Hironobu
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.757.3
Subject(s) - wnt signaling pathway , wnt3a , osteoblast , runx2 , biology , microbiology and biotechnology , microrna , cellular differentiation , transcription factor , signal transduction , crosstalk , gene expression , regulation of gene expression , gene , genetics , physics , optics , in vitro
miRNAs play roles in regulating gene expression at the post‐transcriptional level through fine‐tuning of the protein‐encoding gene expression, and are involved mainly in regulating important biological processes in different cell and tissue types, including osteoblast differentiation. Canonical Wnt signaling is also known to play pleotropic roles in regulating cell differentiation during mammalian osteogenesis, although involvement of miRNAs is not established for Wnt signaling in osteoblast differentiation. We examined here the role of candidate miRNAs expressed differentially after Wnt3a expression during osteoblast differentiation. Overexpression of Wnt3a resulted in increased transcription of the alkaline phosphatase gene, but in decreased transcription of the Runx2, collagen 1a and osteocalcin genes in osteoblastic MC3T3‐E1 cells. Analysis of miRNA expression profile showed that 14 miRNAs were up‐regulated and 21 miRNAs were down‐regulated after Wnt3a overexpression in MC3T3‐E1 cells. TGFβ3 is considered to be a candidate target gene that was down‐regulated by one of miRNAs with database search. Transfection of the miRNA mimic into MC3T3‐E1 cells significantly inhibited TGFβ3 mRNA level and then resultant protein expression, whereas overexpression of Wnt3a increased TGFβ3 mRNA level and protein expression. These results suggest that the miRNA is involved in osteoblast differentiation as a critical regulatory factor, mediating Wnt3a signaling pathway and TGFβ3 signaling pathway. Support or Funding Information Authors declare that we have no conflicts of interests.