title: Osteoprotective effect of combination therapy of low-dose oestradiol with G15, a specific antagonist of GPR30/GPER in ovariectomy-induced osteoporotic rats.
abstract: Identified and cloned in 1996 for the first time, G protein-coupled oestrogen receptor (ER) 30 (GPR30/GPER) has been a hot spot in the field of sex hormone research till now. In the present study, we examined the effects of low-dose oestradiol (E2) combined with G15, a specific antagonist of GPR30 on ovariectomy (OVX)-induced osteoporosis in rats. Female Sprague-Dawley (SD) rats undergoing OVX were used to evaluate the osteoprotective effect of the drugs. Administration of E2 [35 μg/kg, intraperitoneally (ip), three times/week) combining G15 (160 μg/kg, ip, three times/week) for 6 weeks was found to have prevented OVX-induced effects, including increase in bone turnover rate, decrease in bone mineral content (BMC) and bone mineral density (BMD), damage of bone structure and the aggravation in biomechanical properties of bone. The therapeutic effect of these two drugs in combination was better than that of E2 alone. Meanwhile, the administration of G15 prevented body weight increase or endometrium proliferation in the rats. In conclusion, administration of low-dose E2 combining G15 had a satisfactory bone protective effect for OVX rats, without significant influence on body weight or the uterus. This combination therapy may be an effective supplement of drugs in prevention and treatment for postmenopausal osteoporosis.
authors.affiliation: Department of Orthopedics, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China.
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Kang
authors.affiliation: Department of Orthopedics, Jinling Hospital, School of Medicine, Nanjing University, Nanjing 210002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Orthopedics, Yangzhou No 1 People's Hospital, Second Clinical School of Yangzhou University, Yangzhou 225000, China.
authors.forename: Jiang-Ying
authors.initials: JY
authors.lastname: Ru
authors.affiliation: Department of Stomatology, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Si-Qi
authors.initials: SQ
authors.lastname: Ying
authors.affiliation: Department of Ultrasound, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.affiliation: Department of Orthopedics, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China gangliu3@126.com zhaojianning.0207@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Clinical School of Nanjing, Second Military Medical University, Nanjing 210002, China gangliu3@126.com zhaojianning.0207@163.com.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Zhao
mesh_terms: D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology*; D004359:Drug Therapy, Combination / Q000379:methods; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism; D010052:Ovariectomy; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C568862:4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline; D052117:Benzodioxoles; C520305:Gper1 protein, rat; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D004958:Estradiol
keywords: G protein-coupled oestrogen receptor 30 (GPR30/GPER); G15; bone; oestradiol (E2); osteoporosis; ovariectomy (OVX)