title: Myeloid-derived suppressor cells contribute to bone erosion in collagen-induced arthritis by differentiating to osteoclasts.
abstract: 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-κB inhibitor Bay 11-7082 or IκB inhibitor peptide blocked the differentiation of MDSCs to osteoclast and bone resorption. IL-1Ra also blocked this differentiation. In contrast, the addition of IL-1α 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.
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Hui
authors: H
authors: Zhang
authors: Department of Pediatrics, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Yuefang
authors: Y
authors: Huang
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Shuang
authors: S
authors: Wang
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Rong
authors: R
authors: Fu
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Chaohuan
authors: C
authors: Guo
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Hongyue
authors: H
authors: Wang
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Jijun
authors: J
authors: Zhao
authors: Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA 22908-0203, USA.
authors: Felicia
authors: F
authors: Gaskin
authors: Department of Pediatrics, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China.
authors: Jingxian
authors: J
authors: Chen
authors: Department of Rheumatology, First Affiliated Hospital, Sun Yat-sen University, Zhongshan Road II, 510080, Guangzhou, China. Electronic address: zsuyns@163.com.
authors: Niansheng
authors: N
authors: Yang
authors: Division of Rheumatology and Center of Inflammation, Immunology and Regenerative Medicine, Department of Medicine, University of Virginia, Charlottesville, VA 22908-0133, USA; Department of Microbiology, Immunology and Cancer Biology, University of Virginia, Charlottesville, VA 22908-0133, USA.
authors: Shu Man
authors: SM
authors: Fu
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000150:complications*; D001862:Bone Resorption / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism / Q000502:physiology; D053582:Interleukin-1alpha / Q000378:metabolism / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D022423:Myeloid Cells / Q000276:immunology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010010:Osteoclasts / Q000276:immunology*; D053245:RANK Ligand / Q000502:physiology; D013450:Sulfones / Q000494:pharmacology; D013977:Tibia / Q000473:pathology
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D016328:NF-kappa B; D009570:Nitriles; D053245:RANK Ligand; D013450:Sulfones; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor
keywords: Bone destruction; Collagen-induced arthritis and rheumatoid arthritis; MDSC; Osteoclast; Osteoclast precursor