title: Identification of cell cycle-arrested quiescent osteoclast precursors in vivo.
abstract: Osteoclasts are multinucleated cells that resorb bone. Although osteoclasts originate from the monocyte/macrophage lineage, osteoclast precursors are not well characterized in vivo. The relationship between proliferation and differentiation of osteoclast precursors is examined in this study using murine macrophage cultures treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-kappaB (RANK) ligand (RANKL). Cell cycle-arrested quiescent osteoclast precursors (QuOPs) were identified as the committed osteoclast precursors in vitro. In vivo experiments show that QuOPs survive for several weeks and differentiate into osteoclasts in response to M-CSF and RANKL. Administration of 5-fluorouracil to mice induces myelosuppression, but QuOPs survive and differentiate into osteoclasts in response to an active vitamin D(3) analogue given to those mice. Mononuclear cells expressing c-Fms and RANK but not Ki67 are detected along bone surfaces in the vicinity of osteoblasts in RANKL-deficient mice. These results suggest that QuOPs preexist at the site of osteoclastogenesis and that osteoblasts are important for maintenance of QuOPs.
authors.affiliation: Institute for Oral Science, Matsumoto Dental University, Nagano 399-0781, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Mizoguchi
authors.forename: Akinori
authors.initials: A
authors.lastname: Muto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Udagawa
authors.forename: Atsushi
authors.initials: A
authors.lastname: Arai
authors.forename: Teruhito
authors.initials: T
authors.lastname: Yamashita
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hosoya
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nakamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Saya
authors.initials: S
authors.lastname: Kinugawa
authors.forename: Midori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nakamichi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Sakae
authors.initials: S
authors.lastname: Nagasawa
authors.forename: Kimimitsu
authors.initials: K
authors.lastname: Oda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tagaya
authors.forename: Josef M
authors.initials: JM
authors.lastname: Penninger
authors.forename: Michio
authors.initials: M
authors.lastname: Ito
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation / Q000187:drug effects; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*
chemical_list: D053245:RANK Ligand; D002762:Cholecalciferol; D016186:Receptor, Macrophage Colony-Stimulating Factor; D005472:Fluorouracil