Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this s...Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine （CA） repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine （L2-4） PMO patients vs. 92 controls. The （CA）n〈22 and （CA）n≥22 alleles were designated short （S） and long （L）, respectively. ESR2 genotype was categorically defined as SS （2 S alleles）, SL （having the mixed S and L alleles）, and LL （2 L alleles）. At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group （P〈0.01）. The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype （P〈0.05）. After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck （adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001） and the L2-4 （adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023）. This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions.展开更多
Objective To examine the relationship between the vitamin D receptor(VDR) gene polymorphism and osteoporosis in postmenopausal women in Shanghai. Methods 102 postmenopausal women recruited from Ruijin Hospital were os...Objective To examine the relationship between the vitamin D receptor(VDR) gene polymorphism and osteoporosis in postmenopausal women in Shanghai. Methods 102 postmenopausal women recruited from Ruijin Hospital were osteoporotic. We measured the lumbar vertebrae and femur of all patients with a modal dual-energy X-ray absorptionmetry, and also the serum osteocalcin by ELISA. The VDR gene was amplified using a polymerase chain reaction (PCR). The VDR genotypes were determined by the PCR-RFLP. Results bb, aa and TT genotype were found mainly in these osteoporosis patients, only one BB and two tt were found among these patients. No significant association was observed among three subgroups of bb, Bb and BB. Conclusion The rareness of B and t alleles suggested that it is unlikely that they are important factors for the heredity of osteoporosis in Chinese women. Thus VDR gene typing may be of little value in assessing the osteoporosis risk in Chinese population.展开更多
Objective To explore the relationship between vitamin D receptor(VDR)gene polymorphisms and bone mineral density(BMD)in patients with type 2 diabetes mellitus(DM)and to better understand the pathogenesis of osteoporos...Objective To explore the relationship between vitamin D receptor(VDR)gene polymorphisms and bone mineral density(BMD)in patients with type 2 diabetes mellitus(DM)and to better understand the pathogenesis of osteoporosis.Methods Ninety seven patients with type 2 DM were recruited for this study.BMD was measured by single photon absorptiometry at the lower one third of the nondominant radius and ulna.Polymorphisms of the VDR gene were analyzed by DNA amplification with polymerase chain reaction(PCR)and endonuclease digestion with Bsm Ⅰ.Results The respective frequencies of VDR genotypes were BB 18.6%,Bb 27.8% and bb 53.6%.The Z scores of the three groups were - 1.57 ± - 0.60,- 1.45 ± - 0.67 and - 1.41 ± - 0.81,respectively.Although the BMD of the Bb genotype DM patients was higher than that of BB genotype DM patients and lower than that of bb genotype DM patients,there were no significant differences.Conclusion These findings suggest a small influence of VDR gene polymorphism on the BMD of patients with type 2 DM.Further study on the value of VDR genotypes in the pathogenesis of osteoporosis in diabetes mellitus is still needed.展开更多
Insulin-like growth factor-1 receptor(IGF-1 R)is involved in both glucose and bone metabolism.IGF-1 R signaling regulates the canonical Wnt/β-catenin signaling pathway.In this study,we investigated whether the IGF-1...Insulin-like growth factor-1 receptor(IGF-1 R)is involved in both glucose and bone metabolism.IGF-1 R signaling regulates the canonical Wnt/β-catenin signaling pathway.In this study,we investigated whether the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis(DOP).Serum from patients with or without DOP was collected to measure the IGF-1 R level using enzyme-linked immunosorbent assay(ELISA).Rats were given streptozotocin following a four-week high-fat diet induction(DOP group),or received vehicle after the same period of a normal diet(control group).Dual energy X-ray absorption,a biomechanics test,and hematoxylin-eosin(HE)staining were performed to evaluate bone mass,bone strength,and histomorphology,respectively,in vertebrae.Quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were performed to measure the total and phosphorylation levels of IGF-1 R,glycogen synthase kinase-3β(GSK-3β),andβ-catenin.The serum IGF-1 R level was much higher in patients with DOP than in controls.DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group.HE staining showed that the histomorphology of DOP vertebrae was seriously impaired,which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae.PCR analysis demonstrated that IGF-1 R mRNA expression was significantly up-regulated,and western blotting detection showed that phosphorylation levels of IGF-1 R,GSK-3β,andβ-catenin were enhanced in DOP rat vertebrae.Our results suggest that the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of DOP.This may contribute to development of the underlying therapeutic target for DOP.展开更多
文摘Postmenopausal osteoporosis （PMO） is considered a polygenic disease. The estrogen receptor β （ESR2） gene is a candidate mediating the genetic influence on bone mass and the risk of osteoporosis. The aim of this study is to investigate the association of a cytosine-adenine （CA） repeat polymorphism in the fifth intron of the ESR2 gene with PMO in Chinese Han population. The CA repeat polymorphism was genotyped in a case-control study, involving 78 femoral neck PMO patients vs. 122 controls and 108 lumbar spine （L2-4） PMO patients vs. 92 controls. The （CA）n〈22 and （CA）n≥22 alleles were designated short （S） and long （L）, respectively. ESR2 genotype was categorically defined as SS （2 S alleles）, SL （having the mixed S and L alleles）, and LL （2 L alleles）. At both the femoral neck and the L2-4 region, LL genotype and L allele frequencies of the PMO group were significantly higher than those of the control group （P〈0.01）. The subjects with the SL, the LL, and the combined SL and LL genotype had a significant increased risk of PMO when compared with those with the SS genotype （P〈0.05）. After adjustments for age, years since menopause, menopausal age, and body mass index, logistic regression analysis showed that the subjects with the combined SL and LL genotype had increased risk of PMO when compared with those with the SS genotype both at the femoral neck （adjusted OR 4.923, 95% CI 1.986-12.203 , P=0.001） and the L2-4 （adjusted OR 2.267, 95% CI 1.121-4.598, P=0.023）. This extensive association study has identified the ESR2 CA repeat polymorphism to be independently associated with PMO at the femoral neck and the L2-4 in Chinese Han population. The data also suggested that the presence of the L allele may dominantly increase the risk of PMO at the two regions.
文摘Objective To examine the relationship between the vitamin D receptor(VDR) gene polymorphism and osteoporosis in postmenopausal women in Shanghai. Methods 102 postmenopausal women recruited from Ruijin Hospital were osteoporotic. We measured the lumbar vertebrae and femur of all patients with a modal dual-energy X-ray absorptionmetry, and also the serum osteocalcin by ELISA. The VDR gene was amplified using a polymerase chain reaction (PCR). The VDR genotypes were determined by the PCR-RFLP. Results bb, aa and TT genotype were found mainly in these osteoporosis patients, only one BB and two tt were found among these patients. No significant association was observed among three subgroups of bb, Bb and BB. Conclusion The rareness of B and t alleles suggested that it is unlikely that they are important factors for the heredity of osteoporosis in Chinese women. Thus VDR gene typing may be of little value in assessing the osteoporosis risk in Chinese population.
文摘Objective To explore the relationship between vitamin D receptor(VDR)gene polymorphisms and bone mineral density(BMD)in patients with type 2 diabetes mellitus(DM)and to better understand the pathogenesis of osteoporosis.Methods Ninety seven patients with type 2 DM were recruited for this study.BMD was measured by single photon absorptiometry at the lower one third of the nondominant radius and ulna.Polymorphisms of the VDR gene were analyzed by DNA amplification with polymerase chain reaction(PCR)and endonuclease digestion with Bsm Ⅰ.Results The respective frequencies of VDR genotypes were BB 18.6%,Bb 27.8% and bb 53.6%.The Z scores of the three groups were - 1.57 ± - 0.60,- 1.45 ± - 0.67 and - 1.41 ± - 0.81,respectively.Although the BMD of the Bb genotype DM patients was higher than that of BB genotype DM patients and lower than that of bb genotype DM patients,there were no significant differences.Conclusion These findings suggest a small influence of VDR gene polymorphism on the BMD of patients with type 2 DM.Further study on the value of VDR genotypes in the pathogenesis of osteoporosis in diabetes mellitus is still needed.
基金Project supported by the National Natural Science Foundation of China(Nos.81774338 and 81674000)the Natural Science Foundation of Guangdong Province(No.2016A030313645)+1 种基金the Science and Technology Projects of Guangdong Province(No.2016A020226006)the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(2018),China
文摘Insulin-like growth factor-1 receptor(IGF-1 R)is involved in both glucose and bone metabolism.IGF-1 R signaling regulates the canonical Wnt/β-catenin signaling pathway.In this study,we investigated whether the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of diabetic osteoporosis(DOP).Serum from patients with or without DOP was collected to measure the IGF-1 R level using enzyme-linked immunosorbent assay(ELISA).Rats were given streptozotocin following a four-week high-fat diet induction(DOP group),or received vehicle after the same period of a normal diet(control group).Dual energy X-ray absorption,a biomechanics test,and hematoxylin-eosin(HE)staining were performed to evaluate bone mass,bone strength,and histomorphology,respectively,in vertebrae.Quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting were performed to measure the total and phosphorylation levels of IGF-1 R,glycogen synthase kinase-3β(GSK-3β),andβ-catenin.The serum IGF-1 R level was much higher in patients with DOP than in controls.DOP rats exhibited strikingly reduced bone mass and attenuated compression strength of the vertebrae compared with the control group.HE staining showed that the histomorphology of DOP vertebrae was seriously impaired,which manifested as decreased and thinned trabeculae and increased lipid droplets within trabeculae.PCR analysis demonstrated that IGF-1 R mRNA expression was significantly up-regulated,and western blotting detection showed that phosphorylation levels of IGF-1 R,GSK-3β,andβ-catenin were enhanced in DOP rat vertebrae.Our results suggest that the IGF-1 R/β-catenin signaling axis plays a role in the pathogenesis of DOP.This may contribute to development of the underlying therapeutic target for DOP.
