Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis |
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Authors: | Taro Tsurukai Nobuyuki Udagawa Kenichiro Matsuzaki Naoyuki Takahashi Tatsuo Suda |
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Institution: | (1) Department of Biochemistry, School of Dentistry, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan, JP |
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Abstract: | We have isolated osteoclast precursors (OCPs) from cocultures of mouse calvarial cells and bone marrow cells without adding
any osteotropic factors. OCPs expressed Mac-1, Mac-2, and Gr-1 antigens but not osteoclast markers such as tartrate-resistant
acid phosphatase (TRAP) and calcitonin receptors, and they differentiated into TRAP-positive cells within 48 h on a fixed
calvarial cell layer pretreated with osteotropic factors such as 1α,25-dihydroxyvitamin D3. In the present study, we investigated the regulatory mechanisms of OCP formation from hemopoietic cells and TRAP-positive
cell formation from OCPs. Calvarial osteoblasts obtained from macrophage-colony stimulating factor (M-CSF) -deficient op/op mice failed to support OCP formation or the differentiation of OCPs into TRAP-positive cells. Both OCP formation and TRAP-positive
cell formation supported by osteoblasts were completely inhibited by osteoclastogenesis inhibitory factor (OCIF, also called
OPG), which is a decoy receptor of osteoclast differentiation factor (ODF; also called TRANCE, RANKL, and OPGL). When bone
marrow cells were cultured for 4 days with soluble ODF (sODF/sRANKL) together with M-CSF, OCPs were formed even in the absence
of osteoblasts. When OCPs were treated with sODF/sRANKL and M-CSF in the absence of osteoblasts, they differentiated into
TRAP-positive cells within 48 h even in the presence of hydroxyurea. Northern blotting analysis revealed that osteoblasts
constitutively expressed a certain level of ODF/RANKL mRNA. These results indicated that M-CSF and sODF/sRANKL produced by
osteoblasts are two essential factors for both OCP formation and TRAP-positive osteoclast formation.
Received: July 17, 1999 / Accepted: Nov. 12, 1999 |
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Keywords: | : osteoclastogenesis osteoclast macrophage-colony stimulating factor osteoclast precursors osteoclast differentiation factor |
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