title: Osteoprotective effects of estrogen membrane receptor GPR30 in ovariectomized rats.
abstract: G protein-coupled estrogen receptor 30 (GPR30) is expressed in bone tissue. However, little is known regarding the function of GPR30 in postmenopausal osteoporosis. In this study, we examined the effects of GPR30 on ovariectomy (OVX)-induced osteoporosis in rats, including the effects on proliferation, differentiation, and expression of proteins in osteoblasts. Administration of G1 (35 μg/kg, ip, 3 times/week for 6 weeks), a specific agonist of GPR30, prevented OVX-induced increase in bone turnover rate, decrease in bone mineral content and bone mineral density, damage to bone structure, and aggravation of bone biomechanical properties. In addition, G1 did not affect uterine weight in the OVX rats. Osteoblasts isolated from calvarias from newborn rats were used to explore the underlying mechanisms. G1 (150 pM) promoted proliferation and differentiation of osteoblasts through a positive feedback of GPR30, which then activated the PI3K-Akt, ERK, and CREB pathways. G15 (750 pM), a specific antagonist of GPR30, reversed the above effects initiated by G1 treatment. In conclusion, activation of GPR30 protected bones against osteoporosis in OVX rats and exerted no untoward effect on the uterus. We suggest that GPR30 can be used as an effective therapeutic target for the prevention and treatment of postmenopausal osteoporosis.
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Wen-bo
authors.initials: WB
authors.lastname: Kang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ya-ting
authors.initials: YT
authors.lastname: Deng
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Dong-sheng
authors.initials: DS
authors.lastname: Wang
authors.affiliation: Department of Radiology, Tangdu Hospital, Fourth Military Medical University, Xi'an 7l0038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Orthodontic, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xin-shang
authors.initials: XS
authors.lastname: Wang
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Jiang-ying
authors.initials: JY
authors.lastname: Ru
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China. Electronic address: zhaojianning.0207@163.com.
authors.forename: Jian-ning
authors.initials: JN
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. Electronic address: minggao@fmmu.edu.cn.
authors.forename: Ming-gao
authors.initials: MG
authors.lastname: Zhao
authors.affiliation: Jinling Hospital, Department of Orthopedics, Nanjing University, School of Medicine, Nanjing 210002, China. Electronic address: liugene@hotmail.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D009929:Organ Size; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D015398:Signal Transduction; D014599:Uterus
chemical_list: C520305:Gper1 protein, rat; D043562:Receptors, G-Protein-Coupled
keywords: Bone; Estrogen; GPR30; Osteoporosis; Ovariectomy