The small peptide OGP(10-14) reduces proliferation and induces differentiation of TPO-primed M07-e cells through RhoA/TGFbeta1/SFK pathway

Background: Osteogenic growth peptide (OGP) is a 14-mer peptide found in relevant concentration in blood, and its carboxy-terminal fragment [OGP(10-14)] represents the active portion of the full-length peptide. In addition to stimulating bone formation, OGP(10-14) shows hematological activity. In fact, it highly enhances hematopoiesis-affecting stem progenitors. Moreover, OGP(10-14) reduces the growth and induces the differentiation of the hematological tumour cell line trombophoietin(TPO)- primed M07-e by interfering with RhoA and Src kinase pathways. In the present report, we went deeper into this mechanism and evaluated the possible interference of the OGP(10-14) signal pathway with TGFß1 and TPO receptor Mpl. Material/Methods: In OGP(10-14)-treated M07-e cells cultured with or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFß1, Mpl, and Src kinases was analyzed by immunoperoxidase technique. Activated RhoA expression was studied using the G-LISA™ quantitative test. Results: In M07-e cells, both OGP(10-14) and PP2 activate RhoA, inhibit Src kinases, reduce Mpl expression and increase TGFß1 expression. OGP(10-14) and PP2 show the same behavior, causing an additive effect when associated. Conclusions: OGP(10-14) induces TPO-primed M07-e cells differentiation through RhoA/TGFß1/SFKs signaling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the same effects of PP2.