Identification of cell cycle-arrested quiescent osteoclast precursors in vivo

• Published in: The Journal of cell biology Vol. 184; no. 4; pp. 541 - 554
• Main Authors: Mizoguchi, Toshihide, Muto, Akinori, Udagawa, Nobuyuki, Arai, Atsushi, Yamashita, Teruhito, Hosoya, Akihiro, Ninomiya, Tadashi, Nakamura, Hiroaki, Yamamoto, Yohei, Kinugawa, Saya, Nakamura, Midori, Nakamichi, Yuko, Kobayashi, Yasuhiro, Nagasawa, Sakae, Oda, Kimimitsu, Tanaka, Hirofumi, Tagaya, Mitsuo, Penninger, Josef M, Ito, Michio, Takahashi, Naoyuki
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 23.02.2009; Rockefeller University Press
• Subjects: Animals; Biochemistry; Bone marrow cells; Bones; Cell Cycle; Cell Differentiation - drug effects; Cell growth; Cells; Cholecalciferol - analogs & derivatives; Cholecalciferol - pharmacology; Chondrocytes; Cultured cells; Female; Fluorouracil - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Osteoblasts; Osteoblasts - metabolism; Osteoclasts; Osteoclasts - cytology; Osteomyelitis; RANK Ligand - metabolism; Receptor, Macrophage Colony-Stimulating Factor - metabolism; Rodents; Stem cells; Stem Cells - cytology; Vitamin D
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.200806139

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-κB (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 D₃ 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.