Regulation of chondrocytic phenotype by micro RNA 18a: involvement of Ccn2/Ctgf as a major target gene.
We searched for miRNAs that were down-regulated in chondrocytic cells and predicted to target CCN2/connective tissue growth factor (CCN2/CTGF) that promotes endochondral ossification. Among them, expression of miR-18a was most strongly repressed in chondrocytic cells. Reporter gene analysis confirmed the functionality of an miR-18a target in the 3'-untranslated region of Ccn2 mRNA, which was predicted in silico. Indeed, introduction of miR-18a efficiently repressed the CCN2 production from chondrocytic cells. Finally, transfected miR-18a significantly repressed the mature chondrocytic phenotype. Our present study revealed a regulatory role for miR-18a in chondrocytic differentiation through CCN2.
Ohgawara
Toshihiro
T
Department of Biochemistry and Molecular Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, 700-8525, Japan.
Kubota
Satoshi
S
Kawaki
Harumi
H
Kondo
Seiji
S
Eguchi
Takanori
T
Kurio
Naito
N
Aoyama
Eriko
E
Sasaki
Akira
A
Takigawa
Masaharu
M
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000378:metabolism / Q000502:physiology*; D020219:Chondrogenesis / Q000235:genetics*; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D050436:Regulatory Elements, Transcriptional; D012689:Sequence Homology, Nucleic Acid
C526317:CCN2 protein, human; C522576:MIRN18A microRNA, human; D035683:MicroRNAs; D055513:Connective Tissue Growth Factor