Hyemin Jeong1, Eun-Kyung Bae2, Hunnyun Kim2, Dong Hui Lim3, Tae-Young Chung3, Jaejoon Lee4, Chan Hong Jeon1, Eun-Mi Koh4, Hoon-Suk Cha5. 1. Division of Rheumatology, Department of Internal Medicine, Soonchunhyang University Hospital, Bucheon 14584, Republic of Korea. 2. Samsung Biomedical Research Institute, Seoul 06351, Republic of Korea. 3. Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. 4. Division of Rheumatology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. 5. Division of Rheumatology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: hoonsuk.cha@samsung.com.
Abstract
OBJECTIVES: Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse. METHODS: Zymosan was injected intraperitoneally into SKG mice. Clinical arthritis scores were measured, and fluorine-18 fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography (PET/CT) was performed to quantify joint inflammation. Histologic features of the joints, intestines, skin, and eyes were evaluated. Inflammatory cytokine and Wnt inhibitor expression was measured in mouse serum. RESULTS: Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. 18F-FDG uptake was significantly higher in the zymosan-treated mice compared with controls. The expression of tumor necrosis factor α, interleukin (IL)-6, and Dickkopf-1 increased significantly, while IL-4 and sclerostin expression decreased significantly in zymosan-induced mice compared with control mice. CONCLUSIONS: Zymosan-induced SKG mice developed articular and extra-articular features as well as molecular changes that resembled those of human SpA. These findings suggest that the zymosan-induced SKG mouse is a good animal model to reflect the complex features of human SpA.
OBJECTIVES:Spondyloarthritis (SpA) encompasses a group of disorders including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and enteropathic arthritis. SpA pathogenesis is still not well understood. Animal models are important for studying disease mechanisms and identifying new therapeutic agents. Recently, a β-glucan-induced SKG mouse was used as an animal model for SpA. The aim of this study was to evaluate the clinical and molecular characteristics of a zymosan-induced SKG mouse. METHODS:Zymosan was injected intraperitoneally into SKG mice. Clinical arthritis scores were measured, and fluorine-18 fluorodeoxyglucose (18F-FDG) small-animal positron emission tomography/computed tomography (PET/CT) was performed to quantify joint inflammation. Histologic features of the joints, intestines, skin, and eyes were evaluated. Inflammatory cytokine and Wnt inhibitor expression was measured in mouse serum. RESULTS:Zymosan exposure triggered SpA-like diseases in SKG mice, including peripheral arthritis, spondylitis, dactylitis, enteritis, and psoriatic skin lesions. 18F-FDG uptake was significantly higher in the zymosan-treated mice compared with controls. The expression of tumor necrosis factor α, interleukin (IL)-6, and Dickkopf-1 increased significantly, while IL-4 and sclerostin expression decreased significantly in zymosan-induced mice compared with control mice. CONCLUSIONS:Zymosan-induced SKG mice developed articular and extra-articular features as well as molecular changes that resembled those of human SpA. These findings suggest that the zymosan-induced SKG mouse is a good animal model to reflect the complex features of human SpA.