The effect of valproic acid in BMDMs

Currently, the clinical role and influence of valproic acid (VPA) on bone homeostasis remains controversial. In the current study, we confirmed that VPA treatment was linked to a decrease in bone mass and bone mineral density (BMD), an effect that is hypothesized to be caused by a VPA-induced elevation in osteoclast formation and activity. RNA-sequencing revealed a prominent increase of miR-6359 expression in VPA-treated osteoclast precursors which has been demonstrated to be responsible for osteoclast differentiation and bone-resorptive activity. VPA-induced miR-6359 upregulation in osteoclast precursors enhanced ROS production by silencing the SIRT3 protein level, followed by activating the MAPK signaling pathways, which promoted osteoclast formation and activity, thereby accelerating bone loss. To define the expression profile associated with VPA treatment, we conducted an RNA sequencing analysis of mRNA from osteoclast precursors (BMDMs) with VPA or vehicle treatment for 48 hours