Protein kinase D mediates the synergistic effects of BMP-7 and IGF-I on osteoblastic cell differentiation

Lee Chuan C. Yeh, Xiuye Ma, Ronald W. Matheny, Martin L. Adamo, John C. Lee

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

We previously showed that exogenous insulin-like growth factor-I (IGF-I) and bone morphogenetic protein-7 (BMP-7) synergistically stimulated osteoblast differentiation in fetal rat calvaria (FRC) cells. We have now shown that BMP-7 alone and the BMP-7 and IGF-I combination synergistically stimulated protein kinase D (PKD) phosphorylation at Ser744/748 and Ser916. Transfection of FRC cells with a constitutively active PKD stimulated marker expression, while transfection with a catalytically inactive PKD did not. Moreover, Gö6976, which inhibits protein kinase C (PKC) α and β1, blocked PKD phosphorylation and the synergistic action of the BMP-7 and IGF-I combination on osteoblast differentiation, whereas Gö6983, which inhibits PKCα, β, γ, δ, and ζ, did not. Our results suggest that the FRC cell differentiation induced by BMP-7 and the BMP-7 and IGF-I combination requires stimulation of PKD activity. Our results are consistent with a novel mechanism in which combined BMP-7 and IGF-I signaling activates upstream novel PKC(s), which then phosphorylates and activates PKD, leading to enhanced osteoblast differentiation.

Original languageEnglish (US)
Pages (from-to)318-328
Number of pages11
JournalGrowth Factors
Volume28
Issue number5
DOIs
StatePublished - Oct 2010

Keywords

  • BMP-7
  • FRC cultures
  • IGF-I
  • PKD

ASJC Scopus subject areas

  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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