Adenovirus-mediated delivery of Sema3A alleviates rheumatoid arthritis in a serum-transfer induced mouse model
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Yue Teng1, Zhanhai Yin2, Jing Li1, Kun Li3, Xu Li1 and Yan Zhang1
1Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China
2Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, People’s Republic of China
3Clinical Laboratory, Shanxi Mineral Hospital, Xi’an, Shaanxi 710014, People's Republic of China
Yan Zhang, email: [email protected]
Xu Li, email: [email protected]
Keywords: Sema3A, rheumatoid arthritis, serum-transfer induced mouse model, macrophages
Received: May 18, 2017 Accepted: June 28, 2017 Published: August 03, 2017
Rheumatoid arthritis is a chronic autoimmune disease characterized by infiltration of inflammatory cells into the synovium and destruction of cartilage and bone. Macrophages, fibroblast-like synoviocytes (FLS), and osteoclasts are critical cells driving the pathogenesis of RA. Semaphorin 3A (Sema3A) is recently identified as an essential player in the bone homeostasis, however its role in RA progression especially in the macrophage polarization are poorly understood. In the present study, we found that Sems3A levels were significantly decreased in RA serum and synovial fluid compared to OA controls. There was a negative correlation between Sema3A levels and RA severity. Using in vitro cell cultures, we showed for the first time that Sema3A promoted IL-4 induced M2 macrophage polarization, whereas prohibited LPS/IFN-γ induced M1 polarization. Sema3A inhibited VEGF-induced endothelial cells proliferation and migration, suppressed VEGF-mediated invasion and IL-6 production of FLS while stimulating their apoptosis. In addition, Sema3A retarded osteoclastogenesis. In vivo data demonstrated that Sema3A administration attenuated joint tissue damage and the severity of experimental arthritis. Our findings uncovered Sema3A as a promising diagnostic biomarker and novel prevention and treatment strategies in arthritis treatment.
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