title: Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.
abstract: Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC). We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units-fibroblasts (CFU-Fs) assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while pparγ and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (pre)osteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (pre)osteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions.
authors.affiliation: Department of Cytology & Histology, University of Liège, CHU-B23, Liège, Belgium. G.poncin@ulg.ac.be
authors.forename: Géraldine
authors.initials: G
authors.lastname: Poncin
authors.forename: Aurore
authors.initials: A
authors.lastname: Beaulieu
authors.forename: Chantal
authors.initials: C
authors.lastname: Humblet
authors.forename: Albert
authors.initials: A
authors.lastname: Thiry
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.forename: Jacques
authors.initials: J
authors.lastname: Boniver
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Defresne
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects*; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001853:Bone Marrow / Q000528:radiation effects*; D002450:Cell Communication / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D002465:Cell Movement / Q000528:radiation effects; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D054377:Chemokine CXCL12 / Q000378:metabolism; D003114:Colony-Forming Units Assay; D015536:Down-Regulation / Q000528:radiation effects; D005269:Femur / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D039942:Neuropilin-1 / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology / Q000528:radiation effects*; D010641:Phenotype; D014916:Whole-Body Irradiation
chemical_list: D015415:Biomarkers; D054377:Chemokine CXCL12; D039942:Neuropilin-1; D000469:Alkaline Phosphatase