Cartilage contribution to gender differences in joint disease progression. A study with rat articular cartilage

Rheumatoid arthritis is associated with a worse prognosis in females and is influenced by sex hormone changes. Similar observations in osteoarthritis support the hypothesis that gender differences in cartilage make a hitherto unrecognized contribution to gender differences in arthritis. The aim of the present study was to investigate potential gender differences in articular cartilage biochemistry, metabolism and response to inflammatory mediators.

Femoral head cartilages from age-matched male and female Wistar rats were analysed for the water, glycosaminoglycan, hydroxyproline and collagen crosslink contents. 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 investigate gender differences in cartilage susceptibility to erosion caused by granulomatous tissue.

Articular cartilage from male Wistar rats presented higher levels of both proteoglycan and collagen and showed a lower spontaneous glycosaminoglycan loss and higher proteoglycan synthesis in vitro than cartilage from females. Proteoglycan synthesis from female, but not male, cartilage was significantly stimulated by foetal calf serum. Female cartilage was more sensitive to IL-1 inhibition 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 mice, but no differences were observed between male and female cartilage implanted in male mice.

These results demonstrate important gender differences in cartilage biochemistry, metabolism and susceptibility to inflammatory mediators which may have important consequences for the joint destruction in arthritis and support a role for hormone therapy.