Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
| Autor: | Yuichi Yoshida, Kosuke Ebina, Masaru Ishii, Vladimir V. Kalinichenko, Yoshinobu Matsuura, Szandor Simmons, Junichi Kikuta, Tetsuo Hasegawa, Daisuke Okuzaki, Takahiro Matsui, Makoto Hirao, Takao Sudo, Atsushi Hirao, Tsutomu Takeuchi, Kunihiro Yamaoka |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
musculoskeletal diseases
0301 basic medicine Male Immunology Population CX3C Chemokine Receptor 1 Pannus Arthritis Osteoclasts Bone Marrow Cells Mice Transgenic Bone remodeling Arthritis Rheumatoid 03 medical and health sciences Mice 0302 clinical medicine Osteoclast Osteogenesis medicine Immunology and Allergy Macrophage Animals Humans education Cells Cultured education.field_of_study Chemistry Macrophages Forkhead Box Protein M1 Cell Differentiation medicine.disease Arthritis Experimental Thiostrepton In vitro Cell biology Disease Models Animal 030104 developmental biology medicine.anatomical_structure Mice Inbred DBA Homeostasis 030215 immunology |
| Zdroj: | Nature immunology. 20(12) |
| ISSN: | 1529-2916 |
| Popis: | Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80-CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink