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Identification of cell cycle–arrested quiescent osteoclast precursors in vivo

By Toshihide Mizoguchi, Akinori Muto, Nobuyuki Udagawa, Atsushi Arai, Teruhito Yamashita, Akihiro Hosoya, Tadashi Ninomiya, Hiroaki Nakamura, Yohei Yamamoto, Saya Kinugawa, Midori Nakamura, Yuko Nakamichi, Yasuhiro Kobayashi, Sakae Nagasawa, Kimimitsu Oda, Hirofumi Tanaka, Mitsuo Tagaya, Josef M. Penninger, Michio Ito and Naoyuki Takahashi

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-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

Topics: Research Articles
Publisher: The Rockefeller University Press
OAI identifier: oai:pubmedcentral.nih.gov:2654120
Provided by: PubMed Central
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