Osteocytic connexin 43 channels affect fracture healing

The cross-talk between cells is very critical for moving forward fracture healing in an orderly manner. Connexin (Cx) 43-formed gap junctions and hemichannels mediate the communication between adjacent cells and cells and extracellular environment. Loss of Cx43 in osteoblasts/osteocytes results in delayed fracture healing. For investigating the role of two channels in osteocytes in bone repair, two transgenic mouse models with Cx43 dominant negative mutants driven by a 10kb-DMP1 promoter were generated: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Delta 130-136 (both gap junctions and hemichannels are blocked). R76W mice (promotion of hemichannels) showed a significant increase of new bone formation, whereasdelayed osteoclastogenesis and healing was observed in Delta 130-136 (impairment of gap junctions), but not in R76W mice (hemichannel promotion may recover the delay). These results suggest that gap junctions and hemichannels play some similar and cooperative roles in bone repair.