CARTILAGE CONTRIBUTION TO GENDER DIFFERENCES IN JOINT DISEASE PROGRESSION - A STUDY WITH RAT ARTICULAR-CARTILAGE

Objective. Rheumatoid arthritis is associated with a worse prognosis i n females and is influenced by sex hormone changes. Similar observatio ns in osteoarthritis support the hypothesis that gender differences in cartilage make a hitherto unrecognized contribution to gender differe nces in arthritis. The aim of the present study was to investigate pot ential gender differences in articular cartilage biochemistry, metabol ism and response to inflammatory mediators. Methods. Femoral head cart ilages from age-matched male and female Wistar rats were analysed for the water, glycosaminoglycan, hydroxyproline and collagen crosslink co ntents. Proteoglycan loss and synthesis were assessed in vitro, and in the presence and absence of serum and interleukin-1. An in vivo model of inflammation-induced cartilage degradation was employed to investi gate gender differences in cartilage susceptibility to erosion caused by granulomatous tissue. Results. Articular cartilage from male Wistar rats presented higher levels of both proteoglycan and collagen and sh owed a lower spontaneous glycosamninoglycan loss and higher proteoglyc an synthesis in vitro than cartilage from females. Proteoglycan synthe sis from female, but not male, cartilage was significantly stimulated by foetal calf serum. Female cartilage was more sensitive to IL-1 inhi bition of proteoglycan synthesis while the opposite was observed in IL -1-induced proteoglycan loss. Female cartilage was more susceptible to granuloma-induced degradation than male when implanted into female mi ce, but no differences were observed between male and female cartilage implanted in mate mice. Conclusion. These results demonstrate importa nt gender differences in cartilage biochemistry, metabolism and sucept ibility to inflammatory mediators which may have important consequence s for the joint destruction in arthritis and support a role for hormon e therapy.