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Osteocytic connexin 43 channels affect fracture healing |
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| Authors: | Yunhe Chen Meng Chen Tong Xue Guobin Li Dongen Wang Peng Shang Jean X Jiang Huiyun Xu |
| Institution: | 1. Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China
These authors contributed equally to this study.;2. Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi, China;3. Key Laboratory for Space Bioscience and Biotechnology, Research & Development Institute in Shenzhen, Northwestern Polytechnical UniversityShenzhen, Shenzhen, Guangdong, China;4. Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, Texas |
| Abstract: | 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 10 kb-DMP1 promoter were generated: R76W (gap junctions are blocked, whereas hemichannels are promoted) and Δ130–136 (both gap junctions and hemichannels are blocked). R76W mice (promotion of hemichannels) showed a significant increase of new bone formation, whereas delayed osteoclastogenesis and healing was observed in Δ130–136 (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. |
| Keywords: | Cx43 fracture healing gap junction hemichannel transgenic mouse model |