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Am J Physiol Cell Physiol 281: C1917-C1925, 2001;
0363-6143/01 $5.00
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Vol. 281, Issue 6, C1917-C1925, December 2001

Gap junctions and fluid flow response in MC3T3-E1 cells

M. M. Saunders1, J. You1, J. E. Trosko2, H. Yamasaki3, Z. Li1, H. J. Donahue1, and C. R. Jacobs4

1 Musculoskeletal Research Laboratory, Department of Orthopedics and Rehabilitation, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033; 2 Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, Michigan 48824; and 3 Kwansei Gakuin University, Uegahava, Nishinomiya 662-8501, Japan; 4 Biomechanical Engineering Division, Department of Mechanical Engineering, Stanford University, Stanford, California 94304

In the current study, we examined the role of gap junctions in oscillatory fluid flow-induced changes in intracellular Ca2+ concentration and prostaglandin release in osteoblastic cells. This work was completed in MC3T3-E1 cells with intact gap junctional communication as well as in MC3T3-E1 cells rendered communication deficient through expression of a dominant-negative connexin. Our results demonstrate that MC3T3-E1 cells with intact gap junctions respond to oscillatory fluid flow with significant increases in prostaglandin E2 (PGE2) release, whereas cells with diminished gap junctional communication do not. Furthermore, we found that cytosolic Ca2+ (Ca<UP><SUB>i</SUB><SUP>2+</SUP></UP>) response was unaltered by the disruption in gap junctional communication and was not significantly different among the cell lines. Thus our results suggest that gap junctions contribute to the PGE2 but not to the Ca<UP><SUB>i</SUB><SUP>2+</SUP></UP> response to oscillatory fluid flow. These findings implicate gap junctional intercellular communication (GJIC) in bone cell ensemble responsiveness to oscillatory fluid flow and suggest that gap junctions and GJIC play a pivotal role in mechanotransduction mechanisms in bone.

prostaglandin E2; calcium; mechanotransduction; gap junctional intercellular communication


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