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

By Annalisa Facchini, Rosa Maria Borzì and Flavio Flamigni

Abstract

AbstractAmong 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

Publisher: Federation of European Biochemical Societies. Published by Elsevier B.V.
Year: 2005
DOI identifier: 10.1016/j.febslet.2005.04.044
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