FIGURE 7.

A schematic model showing the hemichannel closure after long FFSS is regulated by Cx43 phosphorylation by MAPK, which is activated by extracellular PGE₂ released by hemichannels via feedback inhibition mechanism. During short term FFSS, Cx43 hemichannels (HC) in osteocytes are induced open, which allows the release of bone modulating factors such as PGE₂. A sustained mechanical stimulation causes Cx43 hemichannel closure due to accumulation of PGE₂ in the extracellular environment. The accumulated PGE₂, likely through the EP2/EP4 receptor, activates p44/42 MAPK and increases Cx43 phosphorylation at Ser²⁷⁹-Ser²⁸² residues thereby leading to closure of Cx43 hemichannels.