Role of connexin43 in osteoblast response to physical load.

Gap junctions are hexameric transmembrane channels formed by connexins, and are responsible for direct cell-to-cell communication. The most abundant gap junction protein in bone is connexin43 (Cx43), although connexin45 (Cx45) is also expressed. In the present study, we tested the hypothesis that bone cell responses to mechanical stimulation are dependent on the type of gap junction communication provided by Cx43 in vitro and in an in vivo model of physical load. Application of cyclic stretch to calvaria osteoblasts results in a modest but detectable increase in PGE2 levels, and the amount of PGE2 produced was lower in cells isolated from Cx43 null mice. Mice with an osteoblast-specific deletion of the Cx43 gene were subjected to an in vivo four-point bending protocol on the tibia. This resulted in fast and exuberant formation of woven bone at the region directly below the loading fulcrum in both osteoblast Cx43-deleted and wild-type mice. However, indirect measurement of endosteal bone apposition suggested a less pronounced effect of physical load in Cx43-deficient than in wild-type mice. Taken together, these results indicate that deficiency of Cx43 in osteoblasts attenuates but does not abolish anabolic responses to mechanical strain.