Affiliation:
1. Indiana University School of Medicine
2. Indiana University School of Medicineu
3. Indiana University-Purdue University Indianapolis
4. Cornell University
5. Baylor University
6. Indiana University Purdue University Indianapolis
Abstract
Abstract
Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene premutations lead to fragile X syndrome, cognitive disorders, and, in some individuals, scoliosis and craniofacial abnormalities. Four-month-old male FMR1-deficient mice exhibit a mild increase in cortical and cancellous femoral bone mass. However, consequences of FMR1-deficiency in bone of young and aged and of male and female mice and the cellular basis of the skeletal phenotype remain unknown. We found that FMR1-deficiency results in improved bone properties with higher bone mineral density in both sexes and in 2- and 9-month-old mice. But 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-month-old female FMR1-deficient mice. Further, male bones show higher biomechanical properties in 2-month-old, and females at both ages. FMR1-deficiency increases osteoblast number, mineralization, and bone formation and osteocyte dendricity and gene expression in vivo, ex vivo, and in vitro, without affecting osteoclasts in vivo or ex vivo. Thus, FMR1 is a novel osteoblast/osteocyte differentiation inhibitor, and its absence leads to age-, site- and sex-dependent higher bone mass and strength.
Publisher
Research Square Platform LLC
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