Connexin 43 hemichannel opening associated with Prostaglandin E2 release is adaptively regulated by mechanical stimulation

Abstract

Osteocytes present in the bone are known to be the major mechanosensory cells. Their involvement in mechanoregulation of bone remodeling is not yet clear. Osteocytes are connected with each other thorough gap junctions formed by Connexin 43 (Cx43). Apart from forming gap junctions; Cx43 in osteocytes is also present in the form of hemichannels. Recently, we have developed a unique antibody that specifically blocks hemichannels and does not have any effect on gap junctions. Cx43 hemichannels present in osteocytes of the bone are mechanosensory in nature as they open when subjected to mechanical stimulation in the form of fluid flow shear stress (FFSS). Opening of Cx43 hemichannels results in the release of molecules like PGE2 that are involved in bone remodeling. Our recent report shows that the opening of Cx43 hemichannels depends on the magnitude and duration of shear stress. When osteocytes are subjected to FFSS followed by a brief incubation and reapplication of FFSS, it led to further increase in opening of Cx43 hemichannels. Application of continuous FFSS for longer periods of time (24 hrs) results in decreased opening of hemichannels. These results show that Cx43 hemichannels are adaptive in response to mechanical stimulation, possibly to regulate the release PGE2 during bone remodeling.