title: The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol.
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.
authors.affiliation: Department of Orthopedic Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88#, 310009 Hangzhou, People's Republic of China.
authors.forename: Weijun
authors.initials: W
authors.lastname: Li
authors.forename: Luping
authors.initials: L
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xindie
authors.initials: X
authors.lastname: Zhou
authors.forename: Lidong
authors.initials: L
authors.lastname: Wu
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000378:metabolism / Q000627:therapeutic use*; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism* / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D000077289:Letrozole; D053509:Matrix Metalloproteinase 13 / Q000235:genetics; D019278:Matrix Metalloproteinase 3 / Q000235:genetics; D009570:Nitriles / Q000627:therapeutic use; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D047072:Aromatase Inhibitors; D004965:Estrogen Antagonists; D009570:Nitriles; D019715:Tissue Inhibitor of Metalloproteinase-1; D014230:Triazoles; D000077267:Fulvestrant; D003687:Dehydroepiandrosterone; D004958:Estradiol; D000077289:Letrozole; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3