Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts

Author: Zhang, H.; Huang, Y.; Wang, S.; Fu, R.; Guo, C.; Wang, H.; Zhao, J.; Gaskin, F.; Chen, J.; Yang, N.; Fu, S.M.

Description: Bone erosion is a sign of severe rheumatoid arthritis and osteoclasts play a major role in the bone resorption. Recently, myeloid-derived suppressor cells (MDSC) has been reported to be increased in collagen-induced arthritis (CIA). The number of circulating MDSCs is shown to correlate with rheumatoid arthritis. These findings suggest that MDSCs are precursor cells involved in bone erosion. In this study, MDSCs isolated from mice with CIA stimulated with M-CSF and RANKL in vitro expressed osteoclast markers and acquired osteoclast bone resorption function. MDSCs sorted from CIA mice were transferred into the tibia of normal DBA/1J mice and bones were subjected to histological and Micro CT analyses. The transferred CIA-MDSCs were shown to differentiate into TRAP(+) osteoclasts that were capable of bone resorption in vivo. MDSCs isolated from normal mice had more potent suppressor activity and much less capability to differentiate to osteoclast. Additional experiments showed that NF-kappaB inhibitor Bay 11-7082 or IkappaB inhibitor peptide blocked the differentiation of MDSCs to osteoclast and bone resorption. IL-1Ra also blocked this differentiation. In contrast, the addition of IL-1alpha further enhanced osteoclast differentiation and bone resorption. These results suggest that MDSCs are a source of osteoclast precursors and inflammatory cytokines such as IL-1, contributing significantly to erosive changes seen in rheumatoid arthritis and related disorders.

Subject Headings: Animals; Arthritis, Experimental/complications; Bone Resorption/immunology; Cell Differentiation/drug effects; Cells, Cultured; Interleukin 1 Receptor Antagonist Protein/metabolism/physiology; Interleukin-1alpha/metabolism/physiology; Macrophage Colony-Stimulating Factor/physiology; Male; Mice; Mice, Inbred DBA; Myeloid Cells/immunology; NF-kappa B/antagonists & inhibitors/physiology; Nitriles/pharmacology; Osteoclasts/immunology; RANK Ligand/physiology; Sulfones/pharmacology; Tibia/pathology; Bone destruction; Collagen-induced arthritis and rheumatoid arthritis; Mdsc; Osteoclast; Osteoclast precursor

Keywords: Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts

Publication year: 2015

Journal or book title: Journal of Autoimmunity

Volume: 65


Pages: 82-89

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Type: Journal Article

Serial number: 2592