Bone and bone marrow interactions: hematological activity of osteoblastic growth peptide (OGP)-derived carboxy-terminal pentapeptide III. Action on human megakaryocytopoiesis: focus on essential thrombocythemia.
The increase of megakaryocytes and platelets that characterizes essential thrombocythemia (ET) appears to be secondary to a deregulation of megakaryocytopoiesis. The carboxy-terminal fragment of osteogenic growth peptide (OGP10-14) promotes bone formation and hemopoiesis, while it inhibits megakaryocytopoiesis. In this paper we show that treatment with synthetic OGP10-14 (sOGP10-14) induces a significant reduction of mid and large colony-forming unit-megakaryocytes (CFU-Mk) in ET patients as well as in controls, and is associated with a significant inhibition of thrombopoietin (TPO)-primed MO-7e megakaryoblastic cells proliferation. These actions appear to be related to sOGP10-14 modulation of TGF-beta(1) synthesis and/or secretion, although a direct effect on TGF-beta receptor expression cannot be excluded.
Department of Oncology, Transplants and Advanced Technologies in Medicine, Hematology Division, University of Pisa, Ospedale S Chiara, Via Roma 67, Pisa, Italy.
Rita
R
Fazzi
Sara
S
Galimberti
Simone
S
Pacini
Rossana
R
Testi
Antonio
A
Azzarà
Enrico
E
Orciuolo
Luisa
L
Trombi
Maria Rita
MR
Metelli
Mario
M
Petrini
D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004723:Endorphins / Q000494:pharmacology*; D006657:Histones / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry*; D008533:Megakaryocytes / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000187:drug effects; D013329:Structure-Activity Relationship; D013920:Thrombocythemia, Essential / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000187:drug effects
D016207:Cytokines; D004723:Endorphins; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1; C050198:historphin; C074533:osteogenic growth peptide