日本大阪大学Masaru Ishii团队取得一项新进展，他们的研究鉴定到一种由FoxM1调控的新型关节炎相关破骨细胞前体巨噬细胞。相关论文2019年11月18日在线发表于《自然—免疫学》。

研究人员发现，关节翳中的破骨细胞仅起源于循环的骨髓来源的细胞，而不是局部驻留的巨噬细胞。研究人员确定小鼠CX₃CR1^hiLy6C^intF4/80⁺I-A⁺/I-E⁺巨噬细胞（此处称为关节炎相关的破骨细胞巨噬细胞，AtoM）为发炎的滑膜中含有破骨细胞前体的群体，包括与稳态骨重塑中常规破骨细胞前体不同的亚群。他莫昔芬诱导的Foxm1缺失抑制了AtoM在体外和体内分化为破骨细胞的能力。此外，人类类风湿关节炎患者的滑膜样本包含对应于小鼠AtoM的CX₃CR1⁺HLA-DR^hiCD11c⁺CD80-CD86⁺细胞，FoxM1抑制剂thiostrepton抑制了人类破骨细胞形成，从而揭示了类风湿关节炎治疗的潜在靶标。

据悉，破骨细胞具有独特的破坏骨的能力，在稳态骨重塑和关节炎骨侵蚀中发挥关键作用。目前尚不清楚这些不同组织环境中的破骨细胞是否源自单核细胞的相同前体状态。

附：英文原文

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

Author: Tetsuo Hasegawa, Junichi Kikuta, Takao Sudo, Yoshinobu Matsuura, Takahiro Matsui, Szandor Simmons, Kosuke Ebina, Makoto Hirao, Daisuke Okuzaki, Yuichi Yoshida, Atsushi Hirao, Vladimir V. Kalinichenko, Kunihiro Yamaoka, Tsutomu Takeuchi, Masaru Ishii

Issue&Volume: 2019-11-18

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+CD80CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.

DOI: 10.1038/s41590-019-0526-7

Source: https://www.nature.com/articles/s41590-019-0526-7