Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to ...Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing osteoporosis.The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes.However,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity.Therefore,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were collected.Using multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age.We conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive osteoclasts.Our discovery suggests that this may be mediated through DNA methylation.We suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.展开更多
Background: The etiology of adult obesity is still poorly understood. It has been shown that over-weight children suffer from adverse psychological events, but less is known about the association of adverse psychologi...Background: The etiology of adult obesity is still poorly understood. It has been shown that over-weight children suffer from adverse psychological events, but less is known about the association of adverse psychological factors among normal weight children and adult obesity. Aim: The aim of this study was to examine if the exposure of perception of being bullied during childhood could be associated with development of adult obesity. Methods: Adult, same-sexed twin pairs discordant for BMI were identified from the Danish Twin Registry. The twins underwent an interview and a physical examination. Data were analyzed by means of a growth-curve model and an intra-pair comparison. This design controls for other influences of early lifestyle and socio economic status and is therefore a powerful tool to study independent effects of specific exposures. Results: In total 236 (81.7%) of the twin individuals identified participated in the study. Participants who reported having been bullied in school, had attained a BMI which was on average 1.4 kg/m2 (95% CI = 0.2;2.5, p = 0.02) higher than those not bullied. Two other questions on specific types of bullying resulted in BMI that were 1.1 kg/m2 (CI = 0.1;2.2, p = 0.03) and 1.9 kg/m2 (CI = 0.7;3.1, p = 0.002) larger than subjects who had not been exposed to bullying. There was a direct association between intra pair differences in BMI and exposure to bullying. Conclusion: The results of the study could indicate that being bullied during childhood seems be associated with adult obesity.展开更多
Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed t...Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed BCG.Genome-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed.Furthermore,nine distinct cQTLs were found among infants randomized to BCG.Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination.We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals.These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.展开更多
基金This study was financed by the Research Counsel of Lillebaelt Hospitalthe Region of Southern Denmark(15/24819)+3 种基金the Institute of Regional Health Research,University of Southern Denmarkthe Aase Ejnar Danielsen foundation(10-001835)the Fru Astrid Thaysens foundation(ATL 16/02)We particularly wish to thank Annette Ulv for her hard work recruiting the blood donors,Merete Villumsen for her excellent technical assistance on CTX and PINP measurements,and Hellen Kuasne for her kind support in primer selection for pyrosequencing.
文摘Women gradually lose bone from the age of〜35 years,but around menopause,the rate of bone loss escalates due to increasing bone resorption and decreasing bone formation levels,rendering these individuals more prone to developing osteoporosis.The increased osteoclast activity has been linked to a reduced estrogen level and other hormonal changes.However,it is unclear whether intrinsic changes in osteoclast precursors around menopause can also explain the increased osteoclast activity.Therefore,we set up a protocol in which CD14f blood monocytes were isolated from 49 female donors(40-66 years old).Cells were differentiated into osteoclasts,and data on differentiation and resorption activity were collected.Using multiple linear regression analyses combining in vitro and in vivo data,we found the following:(1)age and menopausal status correlate with aggressive osteoclastic bone resorption in vitro;(2)the type I procollagen N-terminal propeptide level in vivo inversely correlates with osteoclast resorption activity in vitro;(3)the protein level of mature cathepsin K in osteoclasts in vitro increases with age and menopause;and(4)the promoter of the gene encoding the dendritic cell-specific transmembrane protein is less methylated with age.We conclude that monocytes are"reprogrammed"in vivo,allowing them to"remember"age,the menopausal status,and the bone formation status in vitro,resulting in more aggressive osteoclasts.Our discovery suggests that this may be mediated through DNA methylation.We suggest that this may have clinical implications and could contribute to understanding individual differences in age-and menopause-induced bone loss.
文摘Background: The etiology of adult obesity is still poorly understood. It has been shown that over-weight children suffer from adverse psychological events, but less is known about the association of adverse psychological factors among normal weight children and adult obesity. Aim: The aim of this study was to examine if the exposure of perception of being bullied during childhood could be associated with development of adult obesity. Methods: Adult, same-sexed twin pairs discordant for BMI were identified from the Danish Twin Registry. The twins underwent an interview and a physical examination. Data were analyzed by means of a growth-curve model and an intra-pair comparison. This design controls for other influences of early lifestyle and socio economic status and is therefore a powerful tool to study independent effects of specific exposures. Results: In total 236 (81.7%) of the twin individuals identified participated in the study. Participants who reported having been bullied in school, had attained a BMI which was on average 1.4 kg/m2 (95% CI = 0.2;2.5, p = 0.02) higher than those not bullied. Two other questions on specific types of bullying resulted in BMI that were 1.1 kg/m2 (CI = 0.1;2.2, p = 0.03) and 1.9 kg/m2 (CI = 0.7;3.1, p = 0.002) larger than subjects who had not been exposed to bullying. There was a direct association between intra pair differences in BMI and exposure to bullying. Conclusion: The results of the study could indicate that being bullied during childhood seems be associated with adult obesity.
基金supported by the Spinoza grant of the Netherlands Organization for Scientific Research and an ERC Advanced Grant(grant number833247)supported by the European Research Council(starting grant ERC-2009-StG-243149)+3 种基金the Novo Nordisk Foundation(research professorship grant to P.A.)the Danish National Research Foundation(grant DNRF108)the DANIDA,European Union FP7,and OPTIMUNISE(grant Health-F3-2011-261375 to the Bandim Health Project)supported by the Hypathia tenure track grant Radboud UMC。
文摘Genetic variation is a key factor influencing cytokine production capacity,but which genetic loci regulate cytokine production before and after vaccination,particularly in African population is unknown.Here,we aimed to identify single-nucleotide polymorphisms(SNPs)controlling cytokine responses after microbial stimulation in infants of West-African ancestry,comprising of low-birth-weight neonates randomized to bacillus Calmette-Gue rin(BCG)vaccine-at-birth or to the usual delayed BCG.Genome-wide cytokine cytokine quantitative trait loci(cQTL)mapping revealed 12 independent loci,of which the LINC01082-LINC00917 locus influenced more than half of the cytokine-stimulation pairs assessed.Furthermore,nine distinct cQTLs were found among infants randomized to BCG.Functional validation confirmed that several complement genes affect cytokine response after BCG vaccination.We observed a limited overlap of common cQTLs between the West-African infants and cohorts of Western European individuals.These data reveal strong population-specific genetic effects on cytokine production and may indicate new opportunities for therapeutic intervention and vaccine development in African populations.
