MicroRNA-874-3p Exerts Skeletal Anabolic Effects Epigenetically During Weaning by Suppressing XXXX .

@entity17029 @entity604 @entity8087 @entity460
UNASSIGNED: Embryonic skeletogenesis and post-natal bone development require the transfer of @entity460 from the mother to the offspring during pregnancy and lactation. Bone resorption in the mother thus becomes elevated during these periods, resulting in significant maternal skeletal loss. There follows an anabolic phase around weaning, during which there is a remarkable recovery of the maternal skeleton. However, the mechanism(s) of this anabolic response remains largely unknown. We identified 8 differentially expressed miRNAs by array profiling, of which miR-874-3p was highly expressed at weaning, a time when @entity604 was noted to recover. We report that this weaning-associated miRNA is an anabolic target. Thus, an agomir of miR-874-3p induced osteoblast differentiation and mineralization. These actions were mediated through the inhibition of @entity17029 expression and enhanced @entity8087 transcriptional activation. When injected in vivo, the agomir significantly increased osteoblastogenesis and mineralization, reversed @entity604 due to ovariectomy, and increased bone strength. We speculate that elevated miR-874-3p expression during weaning enhances bone formation, and that this miRNA may become a potentially exciting therapeutic target for conditions of @entity604 .
