Bone formation is promoted by mechanical stress, and prostaglandins are thought to mediate these effects in osteocytes. Murine osteocyte MLO-Y4 cells in culture release prostaglandins in response to shear stress, but it was unclear how prostaglandins made their way across the membrane. Cherian et al. show that increased presence of unapposed halves of gap junctions (called hemichannels) may provide passage for the prostaglandins. The authors grew the cells in conditions under which the cells did not make physical contact and thus did not form full gap junctions. In cells exposed to fluid flow for 24 hours, release of prostaglandin E2 was inhibited by various pharmacological inhibitors of hemichannels or by treatment of cells with antisense to the gap junction structural molecule connexin 43. Expression of connexin 43 on the cell surface (detected by biotinylation) was enhanced in response to shear stress. The authors propose that hemichannels--which appear to form passive, energy-independent pores that permit molecules of less than 1 kD to pass without selectivity toward the charge of the molecule--may provide a physiological mechanism for release of highly charged anionic prostaglandin molecules from osteocytes.
P. P. Cherian, A. J. Siller-Jackson, S. Gu, X. Wang, L. F. Bonewald, E. Sprague, J. X. Jiang, Mechanical strain opens connexin 43 hemichannels in osteocytes: A novel mechanism for the release of prostaglandin. Mol. Biol. Cell 16, 3100-3106 (2005). [Abstract] [Full Text]