KDELR2 通过 GSK3β/β-catenin 信号通路促进骨髓间充质干细胞成骨分化。
KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway.
机构信息
Department of Orthopedic Surgery of the Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China.
Orthopedics Research Institute of Zhejiang University, No. 88, Jiefang Road, Hangzhou, 310009, China.
出版信息
Cell Tissue Res. 2024 May;396(2):269-281. doi: 10.1007/s00441-024-03884-9. Epub 2024 Mar 12.
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.
骨不连是外科医生面临的一个具有挑战性的骨折并发症。最近发现，赖氨酸天冬氨酸谷氨酸亮氨酸（KDEL）内质网蛋白保留受体 2（KDELR2）参与了成骨不全症。然而，其确切机制尚不清楚。在这项研究中，我们使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 mBMSCs 的成骨分化，而 KDELR2 过表达则产生相反的效果。此外，KDELR2 过表达上调了活性-β-连环蛋白和磷酸化-GSK3β（Ser9）的水平，而 KDELR2 敲低则下调了这些水平。在骨折模型中，过表达 KDELR2 的 mBMSCs 促进了愈合。总之，KDELR2 通过调节 GSK3β/β-连环蛋白信号通路促进 mBMSCs 的成骨作用。
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