@Article{ecn.2007.0099,
AUTHOR = {Carlos González, Paula Abello, Raquel Cepeda, Lorena Salazar, Octavio Aravena, Barbara Pesce, Diego Catalán, Juan C. Aguillón},
TITLE = {Inflammation, synovial angiogenesis and chondroid apoptosis in the evolution of type II collagen-induced arthritis},
JOURNAL = {European Cytokine Network},
VOLUME = {18},
YEAR = {2007},
NUMBER = {3},
PAGES = {127--135},
URL = {http://www.techscience.com/ECN/v18n3/65982},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2007.0099}
}