The effects of estrogens on cartilage degradation using in vivo and in vitro models.

We have investigated the effects of estradiol on cartilage breakdown. The model of arthritis used involved the subcutaneous implantation of rat femoral head cartilage (FHCs) into the dorsal region of female mice. The FHCs had been previously wrapped in sterile 5 mg cotton to provoke the growth of granulomatous tissue adjacent to cartilage. Animals were dosed daily, a day after implantation, for 14 days with either 17 beta-estradiol or tamoxifen at different doses. The FHCs were removed and analysed for glycosaminoglycan (GAG) content. The results demonstrated that estradiol accelerated cartilage breakdown in a dose dependent manner, an effect which is blocked by tamoxifen. In addition, estradiol was found to increase cartilage degradation in an in vitro model using FHCs. This effect was enhanced by the addition of fibroblasts.