J Vet Sci.  2015 Jun;16(2):165-171. 10.4142/jvs.2015.16.2.165.

Micro-computed tomography evaluation and pathological analyses of female rats with collagen-induced arthritis

• Kim YH
• Kang JS

• KMID: 2164525
• DOI: http://doi.org/10.4142/jvs.2015.16.2.165

Abstract

Imaging techniques have been introduced to assess the efficacy and toxicity of developing pharmaceuticals. The purpose of this study was to perform a comprehensive characterization of collagen-induced arthritis (CIA) in rats using micro-computed tomography (micro-CT) and to compare the results with data from conventional pathological examination. Arthritis was induced by collagen in 24 female Wistar rats. Micro-CT and pathological analyses were performed to assess arthritis progression. Micro-CT analysis showed marked joint destruction occurring in a time-dependent manner following collagen administration. Bone volume was significantly decreased in the tibia at weeks 3 and 4 compared to week 0 (p < 0.05 and p < 0.01, respectively). Additionally, percent bone volume was significantly reduced in the tibia at week 4 compared to week 0 (p < 0.05). In contrast, bone surface/bone volume and trabecular separation were significantly increased in the tibia of the animals at week 4 compared to week 0 (p < 0.05). Severe joint destruction with extensive inflammation, erosion of cartilage and bone, and infiltration of inflammatory cells were observed in the knee joints of the collagen-treated rats. Taken together, micro-CT made it possible to quantify CIA lesions and should be performed with pathological examination in rats.

Keyword

arthritis; collagen; micro-computed tomography; pathology

MeSH Terms

Animals
Arthritis, Experimental/chemically induced/*diagnosis
Disease Models, Animal
Female
Pathology, Clinical
Random Allocation
Rats
Rats, Wistar
*X-Ray Microtomography

Figure

• 

  Fig. 1 X-ray projection image along with coronal and sagittal images of the hind knee joint of collagen-treated rats generated by micro-CT. Note the X-ray projection images (A~D), coronal images (E~H), and sagittal images (I~L) at weeks 0, 2, 3, and 4. Joints appeared normal at week 0 while destruction of the bony surface occurred at weeks 2, 3, and 4 in a time-dependent manner.

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  Fig. 2 Micro-CT analysis parameters of the hind knee joint in collagen-treated rats at weeks 0, 2, 3, and 4. *, **Significantly different compared to week 0 (p < 0.05 and p < 0.01, respectively). Values are presented as the mean ± SD.

• 

  Fig. 3 Visualization of osteophytes in micro-CT coronal (A~D) and 3D images (E~H) of the hind knee joint of collagen-treated rats at weeks 0, 2, 3, and 4. Osteophyte development appeared as red coloring surrounding the irregular bone surface at weeks 3 and 4.

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  Fig. 4 Pathological examination of the hind knee joint from rats treated with collagen. (A) Week 0. (B) Week 2. (C) Week 3. (D) Week 4. Note the normal microscopic structure of the joint of the control rat (A). Knee joints of the collagen-treated animals showed severe joint destruction with inflammatory cell infiltration. Cartilage and bone erosion along with enlarged cavities filled with synovial fibroblasts and inflammatory cells appeared in a time-dependent manner (B~D). H&E staining of paraffin-embedded sections from the hind joint of the rats. 200× magnification.

• 

  Fig. 5 Safranin O-fast green staining of the hind knee joint from rats treated with collagen. (A) Week 0. (B) Week 2. (C) Week 3. (D) week 4. Note the normal cartilage structure of the joint in the rats that appeared as red pigmentation at week 0 (A). However, remarkable cartilage destruction was observed in the joint of the collagen-treated rats in a time-dependent manner (B~D). 200× magnification.

• 

  Fig. 6 Pathological scores for the hind knee joint of rats treated with collagen. (A) Infiltration of inflammatory cells. (B) Cartilage degradation. (C) Synovial proliferation. (D) Hyperplasia of chondrocytes. Values represent the mean ± SD.

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