Nonunion is a challenging complication of fractures for the surgeon. Recently the Lys-Asp-Glu-Leu (KDEL) endoplasmic reticulum protein retention receptor 2 (KDELR2) has been found that involved in osteogenesis imperfecta. However, the exact mechanism is still unclear. In this study, we used lentivirus infection and mouse fracture model to investigate the role of KDELR2 in osteogenesis. Our results showed that KDELR2 knockdown inhibited the osteogenic differentiation of mBMSCs, whereas KDELR2 overexpression had the opposite effect. Furthermore, the levels of active-β-catenin and phospho-GSK3β (Ser9) were upregulated by KDELR2 overexpression and downregulated by KDELR2 knockdown. In the fracture model, mBMSCs overexpressing KDELR2 promoted healing. In conclusion, KDELR2 promotes the osteogenesis of mBMSCs by regulating the GSK3β/β-catenin signaling pathway.

对于外科医生来说，骨不连是一种具有挑战性的骨折并发症。最近发现 Lys-Asp-Glu-Leu (KDEL) 内质网蛋白保留受体 2 (KDELR2) 参与成骨不全症。然而，确切的机制仍不清楚。在本研究中，我们利用慢病毒感染和小鼠骨折模型来研究KDELR2在成骨中的作用。我们的结果表明，KDELR2 敲低抑制 mBMSC 的成骨分化，而 KDELR2 过表达则具有相反的作用。此外，活性β-连环蛋白和磷酸化GSK3β（Ser9）的水平因KDELR2过表达而上调，并因KDELR2敲低而下调。在骨折模型中，过度表达 KDELR2 的 mBMSC 促进愈合。总之，KDELR2通过调节GSK3β/β-catenin信号通路促进mBMSC的成骨。