title: A possible mechanism in DHEA-mediated protection against osteoarthritis.
abstract: Dehydroepiandrosterone (DHEA) and its ester form, DHEA-S, are the most abundant steroids in human plasma. Our previous studies showed that DHEA protects against osteoarthritis (OA). The aim of this paper was to explore the possible mechanisms that underlie DHEA-mediated protection against OA. We tested the expression of β-catenin, it was increased significantly in OA. Rabbit cartilage was treated with various concentrations of DHEA in both IL-1β-induced rabbit chondrocytes and in rabbit cartilage from the anterior cruciate ligament transaction-induced OA model. We found DHEA decreased the expression of β-catenin. Then we further activated Wnt/β-catenin signaling by β-catenin transfection and inactivated it by the inhibitor Dickkopf1 in chondrocytes to reveal its role in the pathogenesis of OA. It turns out the protective effect of DHEA was significantly decreased when Wnt/β-catenin signaling was activated, while inactivating Wnt/β-catenin signaling enhanced the effects of DHEA. Therefore, we hypothesize that DHEA probably exerted its chondroprotective effect by regulating Wnt/β-catenin signaling. Our findings demonstrate the critical role of Wnt/β-catenin signaling in DHEA-mediated protection against OA.
authors: 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: Wei-Jun
authors: WJ
authors: Li
authors: 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: Lu-Ping
authors: LP
authors: Tang
authors: 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: Yan
authors: Y
authors: Xiong
authors: 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: Wei-Ping
authors: WP
authors: Chen
authors: 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: Xin-Die
authors: XD
authors: Zhou
authors: 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: Qian-Hai
authors: QH
authors: Ding
authors: Department of Orthopedic Surgery, The Second Affiliated Hospital of Medical College, Zhejiang University, Jie Fang Road 88#, 310009 Hangzhou, People's Republic of China. Electronic address: ldwu@yahoo.com.
authors: Li-Dong
authors: LD
authors: Wu
mesh_terms: D000818:Animals; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000096:biosynthesis* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D053583:Interleukin-1beta / Q000008:administration & dosage / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D060449:Wnt Signaling Pathway / Q000235:genetics; D051176:beta Catenin / Q000096:biosynthesis* / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D051176:beta Catenin; D003687:Dehydroepiandrosterone
keywords: Chondrocyte; Dehydroepiandrosterone; Dickkopf1; Matrix metalloproteinase; Osteoarthritis; β-Catenin