Title |
Bifurcation of osteoclasts and dendritic cells from common progenitors
|
---|---|
Published in |
Blood, October 2001
|
DOI | 10.1182/blood.v98.8.2544 |
Pubmed ID | |
Authors |
Takeshi Miyamoto, Osamu Ohneda, Fumio Arai, Katsuya Iwamoto, Seiji Okada, Katsumasa Takagi, Dirk M. Anderson, Toshio Suda |
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-kappaB ligand (RANKL) or tumor necrosis factor-alpha (TNF-alpha) 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 differentiation 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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Germany | 1 | 1% |
France | 1 | 1% |
India | 1 | 1% |
United Kingdom | 1 | 1% |
Japan | 1 | 1% |
Unknown | 80 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 17 | 20% |
Researcher | 16 | 19% |
Student > Doctoral Student | 8 | 9% |
Professor | 8 | 9% |
Student > Bachelor | 6 | 7% |
Other | 21 | 25% |
Unknown | 9 | 11% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 26 | 31% |
Medicine and Dentistry | 20 | 24% |
Biochemistry, Genetics and Molecular Biology | 16 | 19% |
Immunology and Microbiology | 9 | 11% |
Neuroscience | 2 | 2% |
Other | 0 | 0% |
Unknown | 12 | 14% |