Site‐specific cartilage changes in murine degenerative knee joint disease induced by iodoacetate and collagenase

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Abstract
Degenerative joint disease was induced in the knee joints of mice by intraarticular injection of two different stimuli: iodoacetate and highly purified collagenase. Proteoglycan synthesis was measured in vivo at different time points in four topographical areas of the knee joint (central and peripheral parts of the patella and central parts of the medial and lateral tibial plateaus) and was compared with histological observations of localized damage to the joint. In vitro incubation with iodoacetate had a direct effect on proteoglycan metabolism. Intra-articular injection of iodoacetate in vivo inhibited the proteoglycan synthesis in cartilage from the central part of the patella. In the peripheral part of the patella, inhibition on day 1 was followed by stimulation of synthesis on days 3–30. Proteoglycan synthesis also was inhibited in the central parts of the medial and lateral tibial plateaus. The areas with inhibited synthesis had loss of safranin O staining on histology. In vitro incubation with collagenase did not have a direct effect on the proteoglycan metabolism of intact cartilage; this led to the assumption that osteoarthritis after injection of collagenase is caused by ligamentous injury, which leads to an unstable joint. Injection of collagenase in vivo stimulated the proteoglycan synthesis in cartilage from the central and peripheral parts of the patella. In an early stage of the process, the cartilage from the tibial plateaus also was slightly stimulated. From 30 days after injection of collagenase, synthesis in the lateral tibial plateau decreased, whereas synthesis in the patella remained stimulated and synthesis in the medial tibial plateau remained normal. On histology, cartilage from the patella and the medial tibial plateau had a normal appearance, and there was loss of cartilage from the lateral tibial plateau. Our data indicate that the variation in response of cartilage from different anatomical areas of the knee joint depends on the stimulus used. This suggests that the location of cartilage damage depends on the etiological factor responsible for induction of the osteoarthritic process.