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Assessment of collagen antibody-induced arthritis in BALB/c mice using bioimaging analysis and histopathological examination


The aim of this study was to examine the therapeutic potential of sulfasalazine and prednisolone in a mouse collagen antibody-induced arthritis (CAIA) model. Twenty-five male BALB/c mice were randomly divided into five groups: group 1 (G1): control, group 2 (G2): probe control, group 3 (G3): CAIA, group 4 (G4): CAIA+sulfasalazine (10 mg/kg, oral), and group 5 (G5): CAIA+prednisolone (100 mg/kg, oral). Fluorescence bioimaging was performed in vivo 24 and 48 h after treatment with a fluorescence probe (OsteoSense 680 EX), and all mice were sacrificed. The hind knee joints were fixed in 10% neutral phosphate-buffered formalin, and micro-computed tomography (micro-CT) and histopathological analyses were performed. The paw thickness increased in a time-dependent manner in G3 mice, but trended toward a decrease in both G4 and G5 mice. Fluorescence intensity increased in G3 mice at 24 and 48 h after fluorescence probe treatment, but the fluorescence intensity in G4 and G5 mice was lower than that in G3. Micro-CT analyses showed that the joint surfaces of G3 mice had a rough and irregular articular appearance, but the occurrence of these irregularities was lower in G4 and G5. Hematoxylin and eosin and Safranin O-fast green staining confirmed that destruction of the cartilage and bony structures, synovial hyperplasia, and inflammatory cell infiltration all occurred in G3, and that the occurrence of these phenomena was lower in G4 and G5 than in G3. Taken together, these results suggest that sulfasalazine and prednisolone can reduce acute rheumatoid arthritis in mice.


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We would like to thank Drs. Kwangmeyung Kim and Hong Yeol Yoon (Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology) for their help of fluorescent bioimaging and Ms. Yeon Soo Choi and Hae Lee Park (Namseoul University) for their technical assistance. This study was supported by a grant of O-song Medical Innovation Foundation R&D project (HO13C0007) of Ministry of Health and Welfare in South Korea.

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Correspondence to Jin Seok Kang.

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Sim, J.H., Lee, W.K., Lee, Y.S. et al. Assessment of collagen antibody-induced arthritis in BALB/c mice using bioimaging analysis and histopathological examination. Lab Anim Res 32, 135–143 (2016).

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  • Mice
  • collagen antibody-induced arthritis
  • sulfasalazine
  • prednisolone fluorescence bioimaging
  • micro-computed tomography