Pannexin-1 and P2X7-Receptor Are Required for Apoptotic Osteocytes in Fatigued Bone to Trigger RANKL Production in Neighboring Bystander Osteocytes

摘要: Osteocyte apoptosis is required to induce intracortical bone remodeling after microdamage in animal models, but how apoptotic osteocytes signal neighboring "bystander" cells initiate the process unknown. Apoptosis has been shown open pannexin-1 (Panx1) channels release adenosine diphosphate (ATP) as a "find-me" for phagocytic cells. To address whether use this signaling mechanism, we adapted rat ulnar fatigue-loading model reproducibly introduce into mouse cortical and measured subsequent changes osteocyte apoptosis, receptor activator of NF-κB ligand (RANKL) expression osteoclastic resorption wild-type (WT; C57Bl/6) mice genetically deficient Panx1 (Panx1KO). Mouse loading produced linear microcracks comparable number location model. WT showed increased RANKL at sites 3 days endocortical tunneling day 14. With fatigue, Panx1KO exhibited levels identical mice. However, they did not upregulate bystander or resorption. interacts with P2X7 R ATP release; thus, examined R-deficient treated antagonist Brilliant Blue G (BBG) test possible role find-me signal. RKO failed despite normally elevated fatigue loading. Similarly, treatment fatigued C57Bl/6 BBG mimicked behavior both mice; had no effect on completely prevented increases attenuated activation by more than 50%. These results indicate that are trigger production implicate an essential mediating process.