MicroRNA-208 modulates BMP-2-stimulated mouse preosteoblast differentiation by directly targeting V-ets erythroblastosis virus E26 oncogene homolog 1

J Biol Chem. 2010 Sep 3;285(36):27745-52. doi: 10.1074/jbc.M110.105080. Epub 2010 Jun 24.

Abstract

MicroRNAs (miRs) represent a class of endogenous approximately 18-25 nucleotide RNAs that regulate gene expression through translational repression by binding to a target mRNA. These miRs regulate several biological functions, such as cell growth, cell differentiation, carcinogenesis, and so on. In a previous report, we have indicated that miR-141 and -200a act as preosteoblast differentiation modulators. In the present study, using microRNA array and in silico analyses, we found that miR-208 is closely involved in preosteoblast differentiation by partially regulating the expression of Ets1 (V-ets erythroblastosis virus E26 oncogene homolog 1), which transactivates osteopontin, runt-related transcription factor 2, parathyroid hormone-related protein, and type I procollagen. Furthermore, the enforced expression of mature miR-208 in murine preosteoblast in MC3T3-E1 cells or primary osteoblast cells remarkably attenuated BMP-2-induced preosteoblast differentiation. In addition, we determined that Ets1 is a target gene of miR-208 by using a sensor luciferase reporter assay. Taken together, these results suggest that the down-regulation of miR-208 in BMP-2-stimulated osteoblast differentiation is an important part of the regulatory machinery involved in early osteogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Blotting, Western
  • Bone Morphogenetic Protein 2 / pharmacology*
  • Cell Differentiation / drug effects*
  • Cell Differentiation / genetics
  • Computational Biology
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Gene Expression Profiling
  • Genes, Reporter / genetics
  • Humans
  • Luciferases / genetics
  • Mice
  • MicroRNAs / genetics*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Osteoblasts / cytology*
  • Osteoblasts / drug effects
  • Osteoblasts / enzymology
  • Osteoblasts / metabolism*
  • Osteogenesis / drug effects
  • Osteogenesis / genetics
  • Proto-Oncogene Protein c-ets-1 / deficiency
  • Proto-Oncogene Protein c-ets-1 / genetics*
  • Rats

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • MicroRNAs
  • Mirn208 microRNA, mouse
  • Proto-Oncogene Protein c-ets-1
  • Luciferases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3