Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1991319 | The Journal of Steroid Biochemistry and Molecular Biology | 2015 | 8 Pages |
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.
Keywords
CTX-ITRAcPBMDOVXGPR30BV/TVSERMsALPAlkaline phosphataseOsteocalcinBoneEstrogentartrate-resistant acid phosphataseOvariectomyBone mineral densitytrabecular separationestrogen replacement therapySerum calciumtrabecular thicknessSerum phosphorusSelective estrogen receptor modulatorscortical areaERTOsteoporosis
Related Topics
Life Sciences
Biochemistry, Genetics and Molecular Biology
Biochemistry
Authors
Wen-bo Kang, Ya-ting Deng, Dong-sheng Wang, Dan Feng, Qian Liu, Xin-shang Wang, Jiang-ying Ru, Yu Cong, Jian-ning Zhao, Ming-gao Zhao, Gang Liu,