The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol

The sex hormone precursor dehydroepiandrosterone (DHEA), which can be converted into estradiol by the enzyme aromatase, has a protective role against osteoarthritis (OA). To determine whether the protective effects of DHEA are dependent on its conversion to estradiol, the aromatase inhibitor letrozole and/or the estrogen receptor inhibitor fulvestrant were administered in the presence of DHEA in both interleukin 1β (IL-1β)-induced rabbit chondrocytes and a rabbit anterior cruciate ligament transaction (ACLT) model of OA. Expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase-1 (TIMP-1) were used to monitor these effects. Expression of MMP-3 and MMP-13 increased in both DHEA-treated chondrocytes and cartilage in the presence of letrozole and/or fulvestrant, while the expression of TIMP-1 and collagen type II (Col-II) decreased. Our findings suggest that the effects of DHEA may be mediated by its conversion to estradiol.

► DHEA has a protective role against osteoarthritis.
► The protective effects of DHEA are attenuated by letrozol and/or fulvestrant.
► The effects of DHEA may be mediated by its conversion to estradiol.