Analysis of Collagen Antibody-induced Arthritis of Mice

국문 초록 (Abstract)

형광바이오이미징과 조직병리학적 분석을 통해 콜라겐 항체유발 관절염(collagen antibody-induced arthritis; CAIA)의 병변양상을 분석하여 보고자 하였다. 수컷 BALB/c 마우스를 세 군으로 나누어 1군과 2군은 0.9% 생리식염수로 처리하고, 3군은 실험 개시일에 anti-type II collagen 5-clone antibody cocktail로 처리한 후 3일째 lipopolysaccharide를 처치하였다. 7일째 형광프로브인 OsteoSense®680EX을 처치하였다. 형광프로브 처치 5시간 후에 avertin 마취하에서 형광강도를 조사하였다. 8일째 마우스는 살처분하고 뒤발 무릎관절을 10% 중성포르말린에 고정하여 조직병리학적 검사를 수행하였다. 형광바이오이미징 검사결과 형광 강도는 1군 혹은 2군과 비교하여 3군의 관절에서 증가되었다. 조직병리학적 검사결과 1군과 2군에서는 염증 혹은 조직손상은 없었다. 3군은 염증세포의 침윤과 활막의 국소적 과형성과 몇몇 연골세포의 미세한 변성이 관찰되었다.
본 실험결과 anti-type II collagen 5-clone antibody cocktail와 lipopolysaccharide에 의해 관절염이 유발되었다. 본 연구결과 형광바이오이미징 검사와 조직병리학적 검사를 통해 생체내 관절염을 검출할 수 있었다.

다국어 초록 (Multilingual Abstract)

Fluorescence bioimaging and histopathological analyses were used to investigate the progression of collagen antibody-induced arthritis (CAIA). Male BALB/c mice were divided separately into three groups. The mice of group 1 (G1) and group 2 (G2) were treated with 0.9% saline and those of group 3 (G3) were boosted with anti-type II collagen 5-clone antibody cocktail at days 0. At day 3, the mice of G1 and G2 were treated with 0.9% saline and those of G3 were treated with lipopolysaccharide. At day 7, mice in G2 and G3 were treated with OsteoSense®680EX. Fluorescence bioimaging was taken at 0, 1, 2, 3, 4, 5, 6, 18 and 24 h after fluorescence probe treatment under anesthesia of avertin. All mice were sacrificed at day 8 after collagen cocktail treatment and all hind knee joints were fixed in 10% neutral phosphate-buffered formalin and histopathological analyses were carried out. Fluorescence bioimaging showed fluorescence intensity was increased in joint of animals in G3 compared to G1 or G2. Histopathological examination of hind joint of mice showed that there was no inflammation or tissue destruction in G1 and G2. In G3, infiltration of inflammatory cells was observed and focal hyperplasia of the synovial lining was observed and some chondrocytes showed slight degeneration. Taken together, in this study, fluorescence bioimaging made it possible to detect the level of arthritis in male mice associated with histopathological examination.

목차 (Table of Contents)

• ABSTRACT
• I. Introduction
• II. Materials and Methods
• III. Results
• IV. Discussion
• V. Conclusion
• References
• 요약

참고문헌 (Reference)

1 D. L. Scott, "Rheumatoid arthritis" 376 (376): 1094-1108, 2010

2 T. Ishikawa, "Prevention of progressive joint destruction in collagen-induced arthritis in rats by a novel matrix metalloproteinase inhibitor, FR255031" 144 (144): 133-143, 2005

3 J. D. Peterson, "Optical tomographic imaging discriminates between disease-modifying anti-rheumatic drug (DMARD) and non-DMARD efficacy in collagen antibody- induced arthritis" 12 (12): R105-, 2010

4 M. de Jong, "Imaging preclinical tumour models: improving translational power" 14 (14): 481-493, 2014

5 L. Bevaart, "Evaluation of therapeutic targets in animal models of arthritis: how does it relate to rheumatoid arthritis?" 62 (62): 2192-2205, 2010

6 D. D. Brand, "Collagen-induced arthritis" 2 (2): 1269-1275, 2007

7 K. S. Nandakumar, "Collagen type II-specific monoclonal antibodyinduced arthritis in mice: description of the disease and the influence of age, sex, and genes" 163 (163): 1827-1837, 2003

8 L. M. Khachigian, "Collagen antibody-induced arthritis" 1 (1): 2512-2516, 2006

9 D. B. Knoerzer, "Clinical and histological assessment of collagen-induced arthritis progression in the diabetes-resistant BB/Wor rat" 25 (25): 13-19, 1997

10 M. Otero, "Cells of the synovium in rheumatoid arthritis" 9 (9): 220-, 2007

11 A. Bendele, "Animal models of rheumatoid arthritis" 1 (1): 377-385, 2001