Induction of ornithine decarboxylase in T/C-28a2 chondrocytes by lysophosphatidic acid: Signaling pathway and inhibition of cell proliferation

Annalisa Facchini, Rosa Maria Borzì, Flavio Flamigni

Research output: Contribution to journalArticlepeer-review

Abstract

Among several extracellular messengers tested, lysophosphatidic acid (LPA) was able to cause the most marked induction of ornithine decarboxylase (ODC) in serum-starved human T/C-28a2 chondrocytes. LPA also induced the activation/phosphorylation of Src, Akt and p44/42 MAPK, and the translocation of PKC-δ from cytosol to membrane coupled to its tyrosine phosphorylation. Experiments with selective signaling inhibitors indicate that LPA leads to Src activation through Gi protein-coupled receptors. In turn Src can activate PI3K and PKC-δ, and all these signaling proteins are required for ODC induction. In conclusion these results show that chondrocytes may be a novel target for LPA action. However, although LPA is considered a mitogen for several cell types and ODC induction is generally correlated to cell growth, LPA was not able to stimulate chondrocyte growth, but rather exerted an anti-proliferative effect.

Original languageEnglish
Pages (from-to)2919-2925
Number of pages7
JournalFEBS Letters
Volume579
Issue number13
DOIs
Publication statusPublished - May 23 2005

Keywords

  • Cell proliferation
  • Chondrocytes
  • Lysophosphatidic acid
  • Ornithine decarboxylase
  • Signal transduction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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