Induction of osteoarthritis by intra-articular injection of collagenase in mice. Strain and sex related differences

To study the effects of strain and sex on the development of injury-induced osteoarthritis (OA) in murine knee joints, two doses of highly purified bacterial collagenase (10 units and 30 units) were injected into male and female mice of two closely related strains, C57BL6 and C57BL10. Frontal histological sections of whole knee joints were made late in the disease process and examined for osteoarthritic lesions. Differences in prevalence of cartilage damage between strains and sexes were observed. Prevalence was higher in C57BL10 (male: almost 100%) than in C57BL6 (male: about 25%), and the prevalence was twice as high in males as in females in both strains. The amount of collagenase (10 or 30 units) did not affect the prevalence of lesions, however, it did influence the severity of the damage. The site of the damage appeared to be dose and strain dependent. Male C57BL6 always showed damage on the medial tibial plateau, independent of dose. In male C57BL10 damage almost always appeared on the lateral tibial plateau with 10 units, while with 30 units the medial plateau also became strongly involved. Since it is known that male mice are more prone to spontaneous OA than female mice and C57BL10 are more prone han C57BL6 mice, it can be concluded that predisposition to spontaneous osteoarthritis increases the risk of developing injury-induced osteoarthritis. Location and severity of the changes will probably be related to joint loadin

Systemic overexpression of interleukin-22 induces the negative immune-regulator SOCS3 and potently reduces experimental arthritis in mice

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Local changes in proteoglycan synthesis during culture are different for normal and osteoarthritic cartilage.

Proteoglycan synthesis of mild-to-moderate osteoarthritic human knee cartilage was compared with that of normal cartilage of the same donor. Immediately after cartilage was obtained, the synthesis rate of proteoglycans was higher for osteoarthritic cartilage than for normal cartilage. Proteoglycan synthesis was then located, for both normal and osteoarthritic cartilage, in the middle and deep zone. However, after 4 days of culture, proteoglycan synthesis rate was higher for normal cartilage than for osteoarthritic cartilage. The reason for this transition from a lower to a higher proteoglycan synthesis rate was a strong increase in the proteoglycan synthesis in the superficial zone of normal cartilage. This was not observed for the osteoarthritic cartilage. The chondrocytes in the superficial zone of osteoarthritic cartilage, in contrast to normal cartilage, were mainly joined in cell clusters and proliferating. This may explain their inability to contribute to proteoglycan synthesis