Bone and bone-marrow interactions: haematological activity of osteoblastic growth peptide (OGP)-derived carboxy-terminal pentapeptide. Mobilizing properties on white blood cells and peripheral blood stem cells in mice.
Osteogenic growth peptide (OGP) increases blood and bone marrow cellularity in mice, and enhances engraftment of bone marrow transplant. Carboxy-terminal pentapeptide (OGP10-14) holds several properties of full-length polypeptide. We evaluated whether synthetic OGP-derived pentapeptide (sOGP10-14) has some activity on peripheral blood cell recovery after cyclophosphamide-induced aplasia, and on stem cell mobilization. Peripheral blood stem cell (PBSC) mobilization was evaluated by administering granulocyte-colony stimulating factor (G-CSF) or sOGP10-14 after cyclophosphamide (CTX) injection. Haematological parameters and CD34/Sca-1 positive cells were sequentially evaluated. Colony-forming tests were performed in bone marrow cells from CTX-, G-CSF- and sOGP10-14-treated mice. sOGP10-14 was able to enhance band cells and monocyte recovery after cyclophosphamide administration. White blood cell (WBC) counts reached the maximum peak by day +10 but, on day +7, a significant recovery was already detected in sOGP10-14 treated mice. On day +10 the WBC increase in sOGP10-14-treated mice was comparable to that found in G-CSF treated ones. Moreover, CD34/Sca-1 positive early precursors were significantly mobilized by sOGP10-14 compared to the control group. In sOGP10-14-treated mice, the colony-forming unit-granulocyte-macrophage-megakaryocyte (GEMM-CFU) and burst-forming unit-erythroid (BFU-E) were significantly increased in bone marrow cells in comparison to mice treated with CTX only. These results suggest a central role of sOGP10-14 in bone and bone marrow interaction, and a possible role of sOGP10-14 as a mobilizing agent.
Fazzi
Rita
R
Department of Oncology, Transplants and Advanced Technologies in Medicine, Hematology Division, University of Pisa, Via Roma 67, 56100, Pisa, Italy.
Testi
Rossana
R
Trasciatti
Silvia
S
Galimberti
Sara
S
Rosini
Sergio
S
Piras
Francesca
F
L'Abbate
Gianluca
G
Conte
Angela
A
Petrini
Mario
M
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity; D001772:Blood Cell Count; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D001842:Bone and Bones / Q000378:metabolism*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003520:Cyclophosphamide / Q000633:toxicity; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010006:Osteoblasts / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology*; D012010:Red-Cell Aplasia, Pure / Q000139:chemically induced / Q000517:prevention & control*
D018952:Antigens, CD34; D018906:Antineoplastic Agents, Alkylating; D006133:Growth Substances; D006657:Histones; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C074533:osteogenic growth peptide; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide