Open Access

ARTICLE

Inflammation, synovial angiogenesis and chondroid apoptosis in the evolution of type II collagen-induced arthritis

Carlos González¹, Paula Abello², Raquel Cepeda¹, Lorena Salazar³, Octavio Aravena², Barbara Pesce², Diego Catalán², Juan C. Aguillón²

1 Departamento de Patología Animal, Facultad de Ciencias Veterinarias y Pecuarias, Universidad de Chile, Santiago, Chile
2 Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile
3 LS is a fellow from Mecesup-Chile, UCH 0115

* Corresponding Author: J.C. Aguillón,

European Cytokine Network 2007, 18(3), 127-135. https://doi.org/10.1684/ecn.2007.0099

Accepted 25 April 2007;

Abstract

Using the murine model of type II collagen-induced arthritis (CIA), we studied its evolution over time by histopathological, immunohistochemical and clinical evaluations. The first clinical symptoms appeared 28 days post-inoculation (dpi), with bovine type II collagen, with an average arthritic index of 1.00 ± 0.48 corresponding to erythema of the articulation. The disease progressed, and by 70 dpi showed an average arthritic index of 3.83 ± 0.27 corresponding to edema and maximum deformation, with ankylosis. Computed morphometry demonstrated that, in comparison to controls, the induction of CIA, produces a significant and increasing accumulation of inflammatory cells, fibrosis (p < 0.0001) and cartilage destruction (p = 0.0029). Likewise, the area of von Willebrand factor (vWF) immunostaining, as an indicator of endothelial proliferation, increased significantly from 28 dpi (p < 0.0001), in CIA mice compared to controls. However, the effective synovial vascularization, calculated as the synovial vascular bed area index, significantly increased by 42 dpi (p = 0.0014). This indicates that the activation and proliferation of endothelium becomes significant before an effective vascularization area is formed. The apoptosis index was also an earlier indicator of cartilage damage, becoming significant from 28 dpi in comparison to controls (p < 0.0001). Finally, it was observed that the increase in the arthritic index showed a strong correlation with the increase in both angiogenesis (r = 0.95; p = 0.0021) and apoptosis (r = 0.90; p = 0.0015). In conclusion, a robust correlation between synovial membrane inflammation, angiogenesis and chondrocyte apoptosis, with respect to the increase in the clinical severity of CIA, has been demonstrated by a quantitative computer-assisted immunomorphometric analysis.

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