Graduate School of Frontier Biosciences, Osaka University


Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Journal Nat Immunol 20, 1631–1643 (2019)
Authors Tetsuo Hasegawa (1, 2), Junichi Kikuta (1, 3), Takao Sudo (1), Yoshinobu Matsuura (1), Takahiro Matsui (1), Szandor Simmons (1), Kosuke Ebina (4), Makoto Hirao (4), Daisuke Okuzaki (5), Yuichi Yoshida (6), Atsushi Hirao (7), Vladimir V. Kalinichenko (8), Kunihiro Yamaoka (2), Tsutomu Takeuchi (2), Masaru Ishii (1, 3)
  1. Department of Immunology and Cell Biology, Graduate School of Medicine and Frontier Biosciences, Osaka University, Osaka, Japan
  2. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
  3. WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan
  4. Department of Orthopaedic Surgery, Osaka University, Osaka, Japan
  5. Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
  6. Department of Gastroenterology and Hepatology, Osaka University, Osaka, Japan
  7. Division of Molecular Genetics, Cancer Research Institute, WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan
  8. Center for Lung Regenerative Medicine, Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA
Title Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
PubMed 31740799
Laboratory Laboratory of Immunology and Cell Biology 〈Prof. Ishii〉
Abstract 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.