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Significance Like other complex disorders, such as diabetes and obesity, osteoporosis is strongly influenced by genetic factors. In this study, we explored the function of the fat mass and obesity-associated gene (FTO), an RNA demethyase that has been strongly linked by genome-wide association studies to obesity and bone density. We show that loss of Fto in mouse osteoblasts leads to age-related bone loss with increased susceptibility of osteoblasts to cell death. RNA profiling of osteoblasts lacking Fto prioritized FTO targets that are members of the DNA repair pathway, which are activated in response to genotoxic stimuli. Our results identify an epigenetic pathway in which FTO normally functions in bone to enhance the stability of mRNA-encoding proteins that protect osteoblasts from genotoxic damage.
Zhang et al. (Wed,) studied this question.