title: Lineage-committed osteoclast precursors circulate in blood and settle down into bone.
abstract: Osteoclasts are derived from the monocyte/macrophage lineage, but little is known about osteoclast precursors in circulation. We previously showed that cell cycle-arrested quiescent osteoclast precursors (QOPs) were detected along bone surfaces as direct osteoclast precursors. Here we show that receptor activator of NF-κB (RANK)-positive cells isolated from bone marrow and peripheral blood possess characteristics of QOPs in mice. RANK-positive cells expressed c-Fms (receptors of macrophage colony-stimulating factor) at various levels, but scarcely expressed other monocyte/granulocyte markers. RANK-positive cells failed to exert phagocytic and proliferating activities, and differentiated into osteoclasts but not into dendritic cells. To identify circulating QOPs, collagen disks containing bone morphogenetic protein-2 (BMP disks) were implanted into mice, which were administered bromodeoxyuridine daily. Most nuclei of osteoclasts detected in BMP-2-induced ectopic bone were bromodeoxyuridine-negative. RANK-positive cells in peripheral blood proliferated more slowly and had a much longer lifespan than F4/80 (a macrophage marker)-positive macrophages. When BMP disks and control disks were implanted in RANK ligand-deficient mice, RANK-positive cells were observed in the BMP disks but not in the controls. F4/80-positive cells were distributed in both disks. Administration of FYT720, a sphingosine 1-phosphate agonist, promoted the egress of RANK-positive cells from hematopoietic tissues into bloodstream. These results suggest that lineage-determined QOPs circulate in the blood and settle in the bone.
authors: Institute for Oral Science, Matsumoto Dental University, Nagano, Japan.
authors: Akinori
authors: A
authors: Muto
authors: Toshihide
authors: T
authors: Mizoguchi
authors: Nobuyuki
authors: N
authors: Udagawa
authors: Susumu
authors: S
authors: Ito
authors: Ichiro
authors: I
authors: Kawahara
authors: Yoshimitsu
authors: Y
authors: Abiko
authors: Atsushi
authors: A
authors: Arai
authors: Suguru
authors: S
authors: Harada
authors: Yasuhiro
authors: Y
authors: Kobayashi
authors: Yuko
authors: Y
authors: Nakamichi
authors: Josef M
authors: JM
authors: Penninger
authors: Toshihide
authors: T
authors: Noguchi
authors: Naoyuki
authors: N
authors: Takahashi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D001842:Bone and Bones / Q000166:cytology* / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D019070:Cell Lineage; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology / Q000378:metabolism; D053245:RANK Ligand / Q000172:deficiency / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D016186:Receptor, Macrophage Colony-Stimulating Factor; D001973:Bromodeoxyuridine