Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors

Sakae Tanaka, Naoyuki Takahashi, Nobuyuki Udagawa, Tatsuya Tamura, Takuhiko Akatsu, E. Richard Stanley, Takahide Kurokawa, Tatsuo Suda

Research output: Contribution to journalArticle

442 Scopus citations

Abstract

The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1α,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1α,25(OH)2D3-stimulated MNC formation. Autoradiographic examination using [3H]-thymidine revealed that osteoclast progenitors primarily proliferated during the first 4 d, whereas their differentiation into MNCs occurred predominantly during the final 2 d of culture in response to 1α,25(OH)2D3. When anti-M-CSF antibody or anti-M-CSF receptor antibody was added either for the first 4 d or for the final 2 d, the MNC formation was similarly inhibited. In co-cultures of normal spleen cells and osteoblastic cells obtained from op/op mice, which cannot produce functionally active M-CSF, the lack of M-CSF either for the first 4 d or for the final 2 d failed to form MNCs in response to 1α,25(OH)2D3 added for the last 2 d. These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalJournal of Clinical Investigation
Volume91
Issue number1
DOIs
StatePublished - Jan 1993

Keywords

  • 1α,25-dihydroxyvitamin D
  • Anti-c-fms antibody
  • Anti-macrophage colony-stimulating factor antibody
  • Osteopetrotic mice

ASJC Scopus subject areas

  • Medicine(all)

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    Tanaka, S., Takahashi, N., Udagawa, N., Tamura, T., Akatsu, T., Stanley, E. R., Kurokawa, T., & Suda, T. (1993). Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. Journal of Clinical Investigation, 91(1), 257-263. https://doi.org/10.1172/JCI116179