Fig. 9

Model of the sodium channel Scn1a in regulating preosteoblast senescence. Scn1a expression is positively regulated by mTORC1 upstream of C/EBPα, whereas its permeability to Na+ is gated by protein kinase A (PKA)-induced phosphorylation. Prosenescent stresses increase the permeability of Scn1a to Na+ by suppressing PKA activity and induce depolarization in preosteoblasts. Depolarization increases Ca2+ influx and activates downstream NFAT/ATF3/p53 signaling, thus promoting preosteoblast senescence