title: Hepatocyte growth factor is secreted by osteoblasts and cooperatively permits the survival of haematopoietic progenitors.
abstract: Human osteoblasts (HOBs) support the growth of human haematopoietic progenitor cells, and support the survival and limited expansion of long-term culture-initiating cells. Using human CD34+ cells and the murine myelomonocytic cell line NFS-60 as targets, we previously found that one component of HOB-derived haematopoietic activity is cell-associated granulocyte colony-stimulating factor (G-CSF). However, antibody failed to neutralize all the activity, suggesting that more than one factor supports haematopoietic cells. In the present investigations, we asked whether the HOB-derived, non-G-CSF secreted activity was as a result of other known growth factors. We found that, among the cytokines expressed by HOBs, only hepatocyte growth factor (HGF) and G-CSF stimulated NFS-60 cell proliferation. HOB cells and osteosarcoma cells secreted biologically active HGF, although the levels varied considerably. Moreover, addition of neutralizing HGF antibody to CD34+ cell/HOB co-cultures resulted in a significant reduction ( approximately 50%) in the ability of the HOBs to support haematopoietic progenitor cells. These results suggest that a major component of osteoblast-derived haematopoietic activity is HGF. Secretion of HGF, in concert with cell-associated cytokines such as G-CSF, may account for the stem cell-stimulating activities of osteogenic cells and, thereby, the unique stem cell-supporting role of the osteoblasts within the bone marrow microenvironment.
authors.affiliation: Department of Periodontics, Prevention and Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, MI, USA. rtaich@umich.edu
authors.forename: R
authors.initials: R
authors.lastname: Taichman
authors.forename: M
authors.initials: M
authors.lastname: Reilly
authors.forename: R
authors.initials: R
authors.lastname: Verma
authors.forename: K
authors.initials: K
authors.lastname: Ehrenman
authors.forename: S
authors.initials: S
authors.lastname: Emerson
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism*; D012516:Osteosarcoma; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D017228:Hepatocyte Growth Factor