Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of ...Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.展开更多
基金supported by the National Institutes of Health R01-AR053643Veterans Research Administration Merit Award I01BX00515+7 种基金a Research Support Funds Grant(RSFG),Indiana University Purdue University Indianapolis-Office of the Vice Chancellor for Research,Indianapolis to LIP.supported by ASBMR Fund for Research and Education Research and Collaborative Grant Programsupported by the National Institutes of Health R01AG067997 to CJHsupported by the IUPUI Diversity Scholars Research Program(DSRP)Diversity Summer Undergraduate Research Opportunity Program(DS-UROP)Indiana CTSI Student Summer Research ProgramIUPUI work study programsupported by the Life Health Science Internship(LHSI)。
文摘Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.
