Abstract
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.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- mBMSCs:
-
Mouse bone marrow mesenchymal stem cells
- ALP:
-
Alkaline phosphatase
- ARS:
-
Alizarin red staining
- shRNA:
-
Short hairpin RNA
- KDELR2:
-
KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- COL1A1:
-
Collagen type I alpha 1 chain
- RUNX2:
-
Runt-related transcription factor 2
- GSK3β:
-
Glycogen synthase kinase 3 beta
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Acknowledgements
We thank the clients who have offered assistance to this study from Clinical Research Center of the second affiliated hospital, Zhejiang university, including Xing Zhang, Meirong Yu, Sicong Chen, Liya Lin, Yunlu Chen, et al. We also appreciate the general help of Linlin Zhang and Shoumin Feng from Orthopedics Research Institute of Zhejiang University.
Funding
This work was supported by the National Natural Science Foundation of China (NO.82172189 and No. 81871759) and the Joint Funds of the Zhejiang Provincial Natural Science Foundation of China (No. LBY21H060004 and No.LY21H070001).
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Deting Xue and Zhijun Pan designed the research; Xiaoyong Wu, Weijun Zhang and Long Long performed the in vitro experiments; Xiaoyong Wu, Yibo Wang, Weijun Zhang, Kanbin Wang and Jinwu Bai performed the in vivo experiments; Xiaoyong Wu and Zhongxiang Wang analyzed the data; Xiaoyong Wu wrote the paper; Deting Xue and Zhijun Pan revised the paper. All authors have read and approved the manuscript.
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All animal experiments were in accordance to the Animal Care and Use Committee guidelines of Zhejiang University. All experimental procedures were in accordance with the and Institutional Animal Care Use Committee at the Second Affiliated Hospital, School of Medicine, Zhejiang University.
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Wu, X., Zhang, W., Long, L. et al. KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway. Cell Tissue Res 396, 269–281 (2024). https://doi.org/10.1007/s00441-024-03884-9
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DOI: https://doi.org/10.1007/s00441-024-03884-9