The appearance of Panx3 and Cx43 relative to other molecules in the cascades of osteoblast differentiation. (A) Panx3 is induced in the transition stage from proliferation to differentiation by BMP2 and Runx2, and promotes cell cycle exit by inhibiting Wnt/β-catenin signaling through its hemichannel. Panx3 also promotes the expression of differentiation marker genes such as Osx and ALP by activating NFAT through the ER Ca2+ channel, CaMKII and calcineurin pathway. At the maturation stage, Panx3 is downregulated and Cx43 is upregulated, concomitant with increased Wnt/β-catenin signaling and decreased BMP2 signaling. (B) Panx3-mediated CaM and NFATc1 signaling increases Osx expression, which promotes Cx43 transcription.