Open AccessInhibition of Complement Retards Ankylosing Spondylitis Progression
Author(s) -
Chaoqun Yang,
Peipei Ding,
Qingkai Wang,
Long Zhang,
Xin Zhang,
Jinqiu Zhao,
Enjie Xu,
Na Wang,
Jianfeng Chen,
Guang Yang,
Weiguo Hu,
Xuhui Zhou
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep34643
Subject(s) - pathogenesis , osteoclast , ankylosing spondylitis , immunology , complement system , medicine , bone marrow , osteoblast , biology , antibody , in vitro , receptor , biochemistry
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 e xtracellular f ibrinogen- b inding 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.