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

• Published in: The Journal of steroid biochemistry and molecular biology 2013-03, Vol.134, p.15-22
• Main Authors: Li, Weijun, Tang, Luping, Xiong, Yan, Zhou, Xindie, Wu, Lidong
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - metabolism; Adjuvants, Immunologic - therapeutic use; Animals; Aromatase Inhibitors - therapeutic use; Cartilage - drug effects; Cartilage - metabolism; Cartilage - pathology; Cells, Cultured; Chondrocyte; Chondrocytes - drug effects; Chondrocytes - metabolism; Chondrocytes - pathology; Dehydroepiandrosterone; Dehydroepiandrosterone - metabolism; Dehydroepiandrosterone - therapeutic use; Estradiol - analogs & derivatives; Estradiol - metabolism; Estradiol - therapeutic use; Estrogen Antagonists - therapeutic use; Female; Fulvestrant; Gene Expression Regulation; Letrozole; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Matrix Metalloproteinase 3 - genetics; Nitriles - therapeutic use; Osteoarthritis; Osteoarthritis - genetics; Osteoarthritis - metabolism; Osteoarthritis - pathology; Osteoarthritis - prevention & control; Rabbits; Tissue Inhibitor of Metalloproteinase-1 - genetics; Triazoles - therapeutic use
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2012.10.001

► 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. 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.