Spontaneous OA occurs in the medial compartment of the knee joint of male and female Hartley albino guinea pigs as well as in other strains of guinea pigs. Although it occurs in both males and females, males tend to grow faster, thus reaching greater body weights and therefore tend to have more consistent pathological alterations. The disease is generally bilaterally symmetrical with respect to incidence and severity and the earliest changes can be seen when animals are approximately 3 months old and weigh about 700 grams. The lesions are initially present on the medial tibial plateau in the area not protected by the meniscus and consist of focal chondrocyte death, proteoglycan loss and fibrillation. Usually about 50% of the animals of this age and weight will have minimal focal changes. The underlying chondrocytes do not exhibit cloning at this stage nor are there morphologic changes in subchondral bone, menisci or synovial membranes. Histopathologic sections must be prepared in the frontal plane in order to observe the medial and lateral aspects of the joint and step sections (200 Ìm) will maximize ability to detect early changes.
When animals are 6 months old and weigh approximately 900 grams, minimal to moderate lesions will be present in 90- 100% of the medial tibial plateaus. Lesions will generally be bilaterally symmetrical. Histopathological features include chondrocyte death/loss extending into the upper middle zone, fibrillation and proteoglycan loss. In addition, cloning extends into the middle and sometimes deep zones and shifts in toluidine blue orthochromatic (blue) to metachromatic (purple) staining of matrix occur, thus indicating changes in proteoglycan synthesis in areas not affected by severe changes leading to fibrillation/ cartilage loss. Small osteophytes are often present at the outer aspect of the medial tibial plateau. Generally there are no obvious subchondral bone changes, meniscal degenerative changes, femoral cartilage degeneration or synovial inflammation at this stage.
Nine-month-old animals will have mild to moderate medial tibial cartilage degeneration, mild femoral condylar degeneration and tibial osteophytes. Mild degenerative changes may be present in the menisci and synovial membranes may be minimally thickened as a result of synoviocyte proliferation. Early sclerosis of subchondral bone may be apparent. By the time the animals are 1 year old, cartilage degenerative changes are usually quite profound and involve all aspects of the medial compartment of the knee. Chondrocyte and proteoglycan loss with fibrillation may extend into the deep zone and cloning is prominent. Subchondral sclerosis is often extensive and subchondral bone cysts are present with severe meniscal degenerative changes.
Because of the very predictable manner in which guinea pigs develop spontaneous knee OA and the obvious similarities to human disease, the model can be used for a variety of purposes including studies of pathogenesis and potential therapeutic intervention.
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