Bifurcation of osteoclasts and dendritic cells from common progenitors

Takeshi Miyamoto, Osamu Ohneda, Fumio Arai, Katsuya Iwamoto, Seiji Okada, Katsumasa Takagi, Dirk M. Anderson, Toshio Suda

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Abstract

Osteoclasts and dendritic cells are derived from monocyte/macrophage precursor cells; however, how their lineage commitment is regulated is unknown. This study investigated the differentiation pathways of osteoclasts and dendritic cells from common precursor cells at the single-cell level. Osteoclastogenesis induced by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-KB ligand (RANKL) or tumor necrosis factor-α (TNF-α) is completely inhibited by addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 at early stages of differentiation. GM-CSF-treated cells express both c-Fms and RANK and also low levels of CD11c and DEC205, which are detected on dendritic cells. Addition of GM-CSF also reduces expression of both c-Fos and Fra-1, which is an important event for inhibition of osteoclastogenesis. Overexpression of c-Fos by retroviral infection or induction in transgenic mice can rescue a failure in osteoclast differentiation even in the presence of GM-CSF. By contrast, differentiation into dendritic cells is inhibited by M-CSF, indicating that M-CSF and GM-CSF reciprocally regulate the differentia tion of both lineages. Dendritic cell maturation is also inhibited when c-Fos is expressed at an early stage of differentiation. Taken together, these findings suggest that c-Fos is a key mediator of the lineage commitment between osteoclasts and dendritic cells. The lineage determination of osteoclast progenitors seen following GM-CSF treatment functions through the regulation of c-Fos expression.

Original languageEnglish
Pages (from-to)2544-2554
Number of pages11
JournalBlood
Volume98
Issue number8
DOIs
Publication statusPublished - Oct 15 2001
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Miyamoto, T., Ohneda, O., Arai, F., Iwamoto, K., Okada, S., Takagi, K., ... Suda, T. (2001). Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood, 98(8), 2544-2554. https://doi.org/10.1182/blood.V98.8.2544