Gap Junctional Intercellular Communication in Bone

Gap junctional intercellular communication has been demonstrated in bone cells and may contribute to the mechanism by which osteoblasts integrate and amplify extracellular signals, both chemical (hormonal) and biophysical (electrical and mechanical). Connexin 43 (Cx43) is the predominant gap junction protein expressed by bone cells. Experiments with osteoblastic cells in which Cx43 expression was diminished by antisense transfection demonstrate that cell-to-cell coupling in osteoblastic ROS 17/2.8 cells is via gap junctions composed of Cx43. Cellular networks of these coupling deficient clones are dramatically less responsive to parathyroid hormone (PTH) suggesting that coupling contributes to hormonal responsiveness. Furthermore, PTH per se can upregulate cell-to-cell communication in these networks. Membrane deformation-induced Ca2+ signals propagate from the deformed cell to neighboring undeformed cells. This phenomenon is blocked by octanol, a gap junction uncoupler. Physiologically relevant electric fields, i.e., induced by mechanical load, stimulate alkaline phosphatase activity in ROS 17/2.8 cells, but this response is greatly reduced in coupling deficient Cx43 antisense transfectants. Furthermore, electric fields per se regulate Cx43 expression in osteoblastic cells. Gap junctional intercellular communication appears critical for the regulation of osteoblastic behavior and thus bone metabolism by extracellular signals