RNA interference of the BMPR-IB gene blocks BMP-2-induced osteogenic gene expression in human bone cells.

W. Singhatanadgit, V. Salih, I. Olsen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have previously shown that human bone cells express bone morphogenetic protein receptor-IB (BMPR-IB). However, little is known about the precise role of this receptor in the response of osteoblastic genes to the BMP in these cells. To determine BMPR-IB-dependent osteoblastic gene expression, the present study examined the effects of BMPR-IB knockdown on BMP-induced osteoblast-associated genes. BMPR-IB mRNA and protein were markedly suppressed by transfection of cells with BMPR-IB siRNA. Using three different bone cell samples, BMP-2 stimulation of alkaline phosphatase (ALP), osteocalcin (OC), distal-less homeobox-5 (Dlx5) and core binding factor alpha-1 (Cbfa1) was found to be specifically and significantly reduced in the BMPR-IB siRNA-transfected cultures compared with that of control cultures. Our study has provided evidence that BMPR-IB-dependent signaling plays a crucial role in BMP-2 up-regulation of the ALP, OC, Dlx5 and Cbfa1 genes in bone cells, suggesting a pivotal role of this receptor in BMP-2-induced osteoblast differentiation in vitro. These findings thus suggest the possibility that BMPR-IB could be a therapeutic target for enhancing bone regeneration in vivo.
Original languageEnglish
Pages (from-to)1362-1370
Number of pages0
JournalCell Biol Int
Volume32
Issue number11
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Alkaline Phosphatase
  • Bone Development
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Protein Receptors
  • Type I
  • Bone Regeneration
  • Cell Differentiation
  • Cells
  • Cultured
  • Core Binding Factor Alpha 1 Subunit
  • Down-Regulation
  • Gene Expression Regulation
  • Developmental
  • Homeodomain Proteins
  • Humans
  • Osteoblasts
  • Osteocalcin
  • Osteogenesis
  • RNA Interference
  • RNA
  • Messenger
  • Small Interfering
  • Transcription Factors
  • Transfection
  • Up-Regulation

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