骨痂形成期白介素IL-6-gp130信号参与骨形成及骨再生。Gαi1/3（G蛋白抑制性α亚单位1/3）是我们证实可介导多种细胞因子信号转导的新型关键信号分子。前期研究发现敲除/敲减Gαi1/3显著抑制IL-6诱导下游AKT和ERK信号的转导；shRNA敲减MC3T-E1中的Gαi1/3后，显著抑制了其成骨能力；在Gαi1/3双敲除鼠中骨小梁显著减少。我们提出Gαi1/3介导IL-6-gp130信号转导促骨损伤修复这一假说。本项目将系统检测小鼠骨不连模型中Gαi1/3、IL-6及gp130等表达情况,解析Gαi介导IL-6-gp130信号转导促成骨作用和分子机制。通过调节骨折端Gαi1/3表达水平，在体研究Gαi1/3调控小鼠骨损伤修复的作用。最后对比观察野生型、Gαi1/3基因敲除/过表达小鼠对骨修复的敏感性差异。拟证实IL-6-gp130-Gαi1/3通路是骨再生修复的关键信号分子。

IL-6-gp130 signaling is important for bone formation and regeneration in the period of callus formation. We have identified Gαi1/3 as a novel and key signal molecule to mediate multiple growth factors signaling. Pilot studies found that Gαi1/3 knockout/knockdown significantly inhibited IL-6-induced downstream AKT and ERK activation. shRNA-mediated knockdown of Gαi1/3 significantly inhibited osteogenic ability of osteogenic precursor cells. The trabecular structure is destroyed in Gαi1/ 3 knockout mice. We propose the hypothesis that Gαi1/3 mediates IL-6 signaling to promote bone regeneration. This project will systematically examine expression of IL-6, gp130 and Gαi1/3 in nonunion model of mice. Research focus will be on the mechanism of Gαi-mediated IL-6-gp130 signal transduction, and the mechanism of Gαi-induced bone regeneration. By regulating the expression of Gαi1/3 at the fracture area, we will study the role of Gαi1/3 in callus formation of mice. Finally, we will compare the sensitivity of bone regeneration between wild-type and Gαi1/3 double knockout mice to verify that IL-6-gp130-Gαi1/3 pathway is an essential signaling pathway in promoting bone regeneration.