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P70 S6 kinase negatively regulates fibroblast growth factor 2-stimulated interleukin-6 synthesis in osteoblasts:

S Takai1, Y Hanai, R Matsushima-Nishiwaki

  • 1Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.

The Journal of Endocrinology
|March 29, 2008
PubMed

Insights

p70 S6 kinase limits interleukin-6 (IL-6) synthesis stimulated by basic fibroblast growth factor (FGF-2) in osteoblasts. Inhibiting p70 S6 kinase enhances IL-6 production, revealing a new regulatory mechanism in bone cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Bone Biology

Background:

  • Protein kinase C (PKC) negatively regulates interleukin-6 (IL-6) synthesis stimulated by basic fibroblast growth factor (FGF-2) in osteoblasts.
  • Interleukin-6 (IL-6) is a key mediator of bone resorption.

Purpose of the Study:

  • To investigate the role of p70 S6 kinase in FGF-2-stimulated IL-6 synthesis in osteoblast-like MC3T3-E1 cells.
  • To elucidate the relationship between protein kinase C (PKC) and p70 S6 kinase in regulating IL-6 production.

Main Methods:

  • Pharmacological inhibition of p70 S6 kinase using rapamycin.
  • Gene silencing of p70 S6 kinase using siRNA.
  • Activation of PKC using 12-O-Tetradecanoylphorbol-13-acetate (TPA).
  • Inhibition of PKC using Go6976 and bisindolylmaleimide I.
  • Assessment of IL-6 synthesis and p70 S6 kinase phosphorylation.

Main Results:

  • Rapamycin and siRNA-mediated downregulation of p70 S6 kinase significantly enhanced FGF-2-stimulated IL-6 synthesis.
  • PKC activation by TPA induced p70 S6 kinase phosphorylation.
  • PKC inhibitors suppressed TPA- and FGF-2-induced p70 S6 kinase phosphorylation.
  • These findings indicate p70 S6 kinase acts downstream of PKC.

Conclusions:

  • p70 S6 kinase negatively regulates FGF-2-stimulated IL-6 synthesis in osteoblasts.
  • PKC signaling pathway influences p70 S6 kinase activity.
  • p70 S6 kinase is a critical downstream mediator in the FGF-2/PKC/IL-6 signaling axis in osteoblasts, impacting bone resorption.

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