title: The small peptide OGP(10-14) reduces proliferation and induces differentiation of TPO-primed M07-e cells through RhoA/TGFbeta1/SFK pathway.
abstract: 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 TGFβ1 and TPO receptor Mpl.
  
  
  METHODS
  In OGP(10-14)-treated M07-e cells cultured with or without RhoA and Src kinases inhibitors (C3 and PP2), expression of TGFβ1, 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 TGFβ1 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/TGFβ1/SFKs signalling pathway. In particular OGP(10-14) acts as a Src inhibitor, showing the same effects of PP2.
authors.affiliation: Department of Human Morphology and Applied Biology, Section of Histology and General Embryology, University of Pisa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Battolla
authors.forename: Nunzia
authors.initials: N
authors.lastname: Bernardini
authors.forename: Mario
authors.initials: M
authors.lastname: Petrini
authors.forename: Letizia
authors.initials: L
authors.lastname: Mattii
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004723:Endorphins / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D004723:Endorphins; D053773:Transforming Growth Factor beta1; C050198:historphin; D020742:rhoA GTP-Binding Protein