Identification of cell cycle-arrested quiescent osteoclast precursors in vivo.
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.
Mizoguchi
Toshihide
T
Institute for Oral Science, Matsumoto Dental University, Nagano 399-0781, Japan.
Muto
Akinori
A
Udagawa
Nobuyuki
N
Arai
Atsushi
A
Yamashita
Teruhito
T
Hosoya
Akihiro
A
Ninomiya
Tadashi
T
Nakamura
Hiroaki
H
Yamamoto
Yohei
Y
Kinugawa
Saya
S
Nakamura
Midori
M
Nakamichi
Yuko
Y
Kobayashi
Yasuhiro
Y
Nagasawa
Sakae
S
Oda
Kimimitsu
K
Tanaka
Hirofumi
H
Tagaya
Mitsuo
M
Penninger
Josef M
JM
Ito
Michio
M
Takahashi
Naoyuki
N
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*
D053245:RANK Ligand; D002762:Cholecalciferol; D016186:Receptor, Macrophage Colony-Stimulating Factor; D005472:Fluorouracil