Conclusion: Alterations in the orientation of the collagen network of the cartilage correlated with Safranin-O loss suggesting that alterations in collagen:PG interactions play a role in the early phases of the OA process and precede frank histologic changes in the articular surface. The results in this study report for the first time OA-like lesions occurring spontaneously in articular cartilage of the ankle in the guinea-pig