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Letizia Mattii, Barbara Battolla, Stefania Moscato, Rita Fazzi, Sara Galimberti, Nunzia Bernardini, Amelio Dolfi, Mario Petrini
Med Sci Monit 2008; 14(6): BR103-108
Osteogenic growth peptide (OGP) is an endogenous tetradecapeptide present in micromolar concentrations in mammalian serum; its carboxy-terminal pentapeptide, OGP(10-14), represents its physiologically active fragment. OGP(10-14) induces proliferation and differentiation in fibroblast and osteoblast cell lines, and it enhances hematopoiesis in vitro and in vivo. The signaling pathways triggered by OGP(10-14) are not yet fully known. In the present report, we evaluated the effect of OGP(10-14) on differentiation of a cancer megakaryoblast cell line and its involvement on RhoA and Src family kinases signaling pathway.
Material and Method: Cell proliferation of the Mo-7e line was evaluated using the MTT test. Mo-7e differentiation was evaluated by microscopic observation of cell morphology and by expression of the factor VIII-related antigen. Involvement of RhoA and Src kinases on signaling pathways triggered by OGP(10-14) was analyzed using RhoA and Src family kinase (SFK) inhibitors (C3 and PP2) and an immunoperoxidase technique.
Results: OGP(10-14) induces expression of the factor VIII-related antigen, morphologic changes indicative of megakaryocytic differentiation, and a down-regulation of the Fyn Src kinase. These OGP(10-14) effects were prevented by C3 and enhanced by PP2.
Conclusions: The anti-proliferative and pro-differentiating activities of OGP(10-14) on thrombopoietin (TPO)-primed Mo-7e cells are mediated by RhoA and Src kinase pathways as demonstrated by the use of C3 and PP2.
Keywords: src-Family Kinases - metabolism, von Willebrand Factor - metabolism, rhoA GTP-Binding Protein - metabolism, Pyrimidines - pharmacology, Proto-Oncogene Proteins c-fyn - metabolism, Intercellular Signaling Peptides and Proteins - pharmacology, Histones - pharmacology, Cell Proliferation - drug effects, Enzyme Activation - drug effects, Cell Line, Cell Differentiation - drug effects, Botulinum Toxins - pharmacology, ADP Ribose Transferases - pharmacology