Article ID Journal Published Year Pages File Type
1991710 The Journal of Steroid Biochemistry and Molecular Biology 2013 8 Pages PDF
Abstract

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.

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Life Sciences Biochemistry, Genetics and Molecular Biology Biochemistry
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