title: Osteoclasts are dispensable for hematopoietic progenitor mobilization by granulocyte colony-stimulating factor in mice.
abstract: The contribution of osteoclasts to hematopoietic stem/progenitor cell (HSPC) retention in the bone marrow is controversial. Studies of HSPC trafficking in osteoclast-deficient mice are limited by osteopetrosis. Here, we employed two non-osteopetrotic mouse models to assess the contribution of osteoclasts to basal and granulocyte colony-stimulating factor (G-CSF)-induced HSPC mobilization. We generated Rank(-/-) fetal liver chimeras using Csf3r(-/-) recipients to produce mice lacking G-CSF receptor expression in osteoclasts. Basal and G-CSF-induced HSPC mobilization was normal in these chimeras. We next acutely depleted osteoclasts in wild-type mice using the RANK ligand inhibitor osteoprotegerin. Marked suppression of osteoclasts was observed after a single injection of osteoprotegerin-Fc. Basal and G-CSF-induced HSPC mobilization in osteoprotegerin-Fc-treated mice was comparable to that in control mice. Together, these data indicate that osteoclasts are not required for the efficient retention of HSPCs in the bone marrow and are dispensable for HSPC mobilization by G-CSF.
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Mahil
authors.initials: M
authors.lastname: Rao
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Teerawit
authors.initials: T
authors.lastname: Supakorndej
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Schmidt
authors.affiliation: Division of Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: dlink@dom.wustl.edu.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Link
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002678:Chimera / Q000235:genetics; D005333:Fetus; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000235:genetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053244:Osteoprotegerin / Q000008:administration & dosage / Q000235:genetics; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000172:deficiency / Q000235:genetics; D016184:Receptors, Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics
chemical_list: D007141:Immunoglobulin Fc Fragments; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016184:Receptors, Colony-Stimulating Factor; D011993:Recombinant Fusion Proteins; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor