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Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
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Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
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Journal Article
Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1
2019
Overview
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 CX
3
CR1
hi
Ly6C
int
F4/80
+
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 CX
3
CR1
+
HLA-DR
hi
CD11c
+
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.
Osteoclasts are a monocytoid cell with unique bone-remodeling capability. Ishii and colleagues demonstrate that the transcription factor FoxM1 is important for the differentiation of osteoclasts associated with pathological remodeling of the rheumatoid joint.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Arthritis, Experimental - immunology
/ Arthritis, Rheumatoid - immunology
/ Biomedical and Life Sciences
/ Bone Marrow Cells - physiology
/ CX3C Chemokine Receptor 1 - metabolism
/ Forkhead Box Protein M1 - antagonists & inhibitors
/ Forkhead Box Protein M1 - genetics
/ Forkhead Box Protein M1 - metabolism
/ Histocompatibility antigen HLA
/ Humans
/ Male
/ Mice
/ Synovium
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