PMID: 9662126Jul 14, 1998Paper

Signal pathways that transduce growth factor-stimulated mitogenesis in bone cells

Bone
J R SandyR W Farndale

Abstract

This investigation examined which signal pathways are of relevance in growth factor-stimulated bone cell mitogenesis. Platelet-derived growth factor (PDGF) and insulin-like growth factor-II (IGF-II) were potent mitogens for both the MG-63 osteoblast cell line and for primary cultures of human osteoblasts (HObs). The mitogenic action of both IGF-II and PDGF was attenuated by pertussis toxin (Ptx), by indomethacin, and by the lipoxygenase inhibitors BW755C74 and BW4AC. A combination of Ptx and indomethacin caused much greater inhibition but failed to abolish mitogenesis completely. PDGF significantly elevated inositol phosphates levels in both cell types; IGF-II had no effect on this pathway. In MG-63 cells, we demonstrated tyrosine phosphorylation of high-molecular-weight substrates elicited by both PDGF and IGF-II. Genistein inhibited the phosphorylation and mitogenic response to PDGF, but had no effect on IGF-II-induced tyrosine phosphorylation or mitogenesis. Another inhibitor of tyrosine kinases, methyl 2,5-dihydroxycinnamate, (MDHC), inhibited PDGF-stimulated mitogenesis effectively in both cell types but only blocked IGF-II-induced mitogenesis in MG-63 cells. The specificity of these inhibitors suggests that particular tyr...Continue Reading

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Citations

Jan 24, 2007·Nature Clinical Practice. Endocrinology & Metabolism·Edward M Brown
Jul 7, 2000·Thyroid : Official Journal of the American Thyroid Association·P LakatosP H Stern
Sep 10, 2004·European Journal of Biochemistry·Lodovica VerganiFederica Dabbeni-Sala
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