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Lineage‐committed osteoclast precursors circulate in blood and settle down into bone
Author(s) -
Muto Akinori,
Mizoguchi Toshihide,
Udagawa Nobuyuki,
Ito Susumu,
Kawahara Ichiro,
Abiko Yoshimitsu,
Arai Atsushi,
Harada Suguru,
Kobayashi Yasuhiro,
Nakamichi Yuko,
Penninger Josef M,
Noguchi Toshihide,
Takahashi Naoyuki
Publication year - 2011
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.490
Subject(s) - osteoclast , haematopoiesis , bone marrow , monocyte , biology , rank ligand , macrophage , microbiology and biotechnology , macrophage colony stimulating factor , precursor cell , immunology , medicine , endocrinology , chemistry , receptor , stem cell , activator (genetics) , cell , osteoprotegerin , biochemistry , in vitro
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. © 2011 American Society for Bone and Mineral Research