Primary osteoarthrosis in guinea pigs

Abstract: The course of primary osteoarthrosis (OA) in Hartley guinea pigs, which spontaneously develop OA in their knee joints, was studied by stereology (quantitative morphology). Between 6 and 12 months of age, structural changes similar to those of human OA developed, predominantly in the central (non meniscus- covered) medial condyle, while the lateral condyle remained unaffected. In the early phases, cartilage fibrillation and subsequent destruction was accompanied by subchondral bone sclerosis. The epiphyseal volume increased predominantly in the medial condyle, indicating a potential for growth and remodelling in the joint. The results support the notion that unbalanced joint growth and remodelling may be a pathogenetic factor in OA. Cartilage destruction was focal, with cell clustering, hypertrophy and increased metachromasia surrounded by a border of grossly intact cartilage. Subjacent to the destructed cartilage, the height of the calcified cartilage increased, and the surface density of bone at the osteocartilaginous interface decreased in the medial condyle. Cysts and osteophytes apparently developed through fibrocartilaginous proliferation. In Hartley guinea pig OA, tissue destruction is thus accompanied by attempts at repair. Surgical load redistribution affected the development of primary guinea pig OA. Redistribution of local load from the medial to the lateral condyle by osteotomy, retarded OA development on the medial side, while increasing development of OA on the lateral side. By amputation, the general load was increased in the non-amputated leg, resulting in augmented OA changes in the cartilage. In contrast, the amputated leg with diminshed load, exhibited reduced OA changes. In both intervention groups, the bone seemed to react more rapidly to a changed mechanical situation than cartilage, the latter probably having a more limited repertoire regarding response to injury/disease. The immunolocalization of two bone matrix proteins, bone sialoprotein (BSP), and osteopontin (OPN) was investigated by electron microscopy of proximal tibias from young rats. Both BSP and OPN were located at the osteocartilaginous interface, where they may have a structural role or regulate mineralization. In situ hybridization showed that BSP was synthesized closer to the osteocartilaginous interface than OPN, suggesting that OPN may be involved in later stages of osteogenesis than BSP. In the guinea pig OA model ultrastructural immunohistochemistry revealed that BSP had a similar distribution at the osteocartilaginous interface as in young rats, a pattern largely unchanged even in the older animals. Immunolabelling was increased in OA, but only in areas of severe changes, indicating that changes in the concentration of BSP is not a suitable marker for early OA. We conclude that the guinea pig model is promising for studies on the molecular events in pathogenesis of OA. Our results demonstrate the close connection between development of pathological changes in cartilage and bone, respectively, and that load beyond a certain level is an important factor.