title: Inhibition of Complement Retards Ankylosing Spondylitis Progression.
abstract: Ankylosing spondylitis (AS) is a chronic axial spondyloarthritis (SpA) resulting in back pain and progressive spinal ankyloses. Currently, there are no effective therapeutics targeting AS largely due to elusive pathogenesis mechanisms, even as potential candidates such as HLA-B27 autoantigen have been identified. Herein, we employed a proteoglycan (PG)-induced AS mouse model together with clinical specimens, and found that the complement system was substantially activated in the spinal bone marrow, accompanied by a remarkable proportion alteration of neutrophils and macrophage in bone marrow and spleen, and by the significant increase of TGF-β1 in serum. The combined treatment with a bacteria-derived complement inhibitor Efb-C (C-terminal of extracellular fibrinogen-binding protein of Staphylococcus aureus) remarkably retarded the progression of mouse AS by reducing osteoblast differentiation. Furthermore, we demonstrated that two important modulators involved in AS disease, TGF-β1 and RANKL, were elevated upon in vitro complement attack in osteoblast and/or osteoclast cells. These findings further unravel that complement activation is closely related with the pathogenesis of AS, and suggest that complement inhibition may hold great potential for AS therapy.
authors.affiliation: Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.|Department of Hand Surgery, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Ding
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Qingkai
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Jianquan
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Enjie
authors.initials: E
authors.lastname: Xu
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Collaborative Innovation Center of Cancer Medicine, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.|Department of Immunology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
authors.forename: Xuhui
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001416:Back Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001426:Bacterial Proteins / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D003165:Complement System Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D061251:Primary Cell Culture; D011509:Proteoglycans / Q000008:administration & dosage; D053245:RANK Ligand / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D013167:Spondylitis, Ankylosing / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D001426:Bacterial Proteins; C114014:Efb protein, Staphylococcus aureus; D011509:Proteoglycans; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; D053773:Transforming Growth Factor beta1; D003165:Complement System Proteins