INFLAMMATION-INDUCED CARTILAGE DEGRADATION IN FEMALE RODENTS - PROTECTIVE ROLE OF SEX-HORMONES

Objective. To investigate the effects of physiologic levels of sex ste roids on inflammation and cytokine production and their consequential cartilage degradation. Methods. We used an in vivo model of inflammati on-induced cartilage degradation in female mice to study the effects o f ovariectomy and hormone treatment, and in vitro culture systems to e xamine the influence of sex steroids on cartilage metabolism, interleu kin-1 (IL-1) production by granulomatous tissue, and its effects on fe male mouse articular cartilage. Results. Ovariectomy resulted in accel erated cartilage breakdown associated with increased production of IL- 1 by granulomatous tissue. The effects of ovariectomy on cartilage wer e reversed by treatment with estradiol and androgen, but not by proges terone treatment. Estradiol and progesterone reduced both spontaneous and IL-1-induced cartilage degradation in vitro. Testosterone antagoni zed the effects of IL-1 on both proteoglycan loss and proteoglycan syn thesis. Conclusion. These data suggest that sex steroids have an impor tant influence on inflammation-induced cartilage breakdown in female a nimals, with protective effects of both estradiol and androgens. Multi ple mechanisms may be involved, and they are likely to include direct immunomodulatory effects as well as interactions with the effects of c ytokine and of the glucocorticoid response to inflammation.