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PGE₂ Is Essential for Gap Junction-Mediated Intercellular Communication between Osteocyte-Like MLO-Y4 Cells in Response to Mechanical Strain

Department of Biochemistry (B.C., L.F.B., J.X.J.), Medicine (S.Z., L.F.B.) and Radiology (J.L., E.S.), University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900; and Asahi Chemical Company (Y.K.), Ohito, Japan

Address all correspondence and requests for reprints to: Jean X. Jiang, Ph.D., Department of Biochemistry, MSC 7760, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900. E-mail: jiangj{at}uthscsa.edu

We have observed, in our previous studies, that fluid flow increases gap junction-mediated intercellular coupling and the expression of a gap junction protein, connexin 43, in osteocyte-like MLO-Y4 cells. Interestingly, this stimulation is further enhanced during the poststress period, indicating that a released factor(s) is likely to be involved. Here, we report that the conditioned medium obtained from the fluid flow-treated MLO-Y4 cells increased the number of functional gap junctions and connexin 43 protein. These changes are similar to those observed in MLO-Y4 cells directly exposed to fluid flow. Fluid flow was found to induce PGE₂ release and increase cyclooxygenase 2 expression. Treatment of the cells with PGE₂ had the same effect as fluid flow, suggesting that PGE₂ could be responsible for these autocrine effects. When PGE₂ was depleted from the fluid flow-conditioned medium, the stimulatory effect on gap junctions was partially, but significantly, decreased. Addition of the cyclooxygenase inhibitor, indomethacin, partially blocked the stimulatory effects of mechanical strain on gap junctions. Taken together, these studies suggest that the stimulatory effect of fluid flow on gap junctions is mediated, in part, by the release of PGE₂. Hence, PGE₂ is an essential mediator between mechanical strain and gap junctions in osteocyte-like cells.

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