KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway.

IF 3.2 3区 生物学 Q3 CELL BIOLOGY
Cell and Tissue Research Pub Date : 2024-05-01 Epub Date: 2024-03-12 DOI:10.1007/s00441-024-03884-9
Xiaoyong Wu, Weijun Zhang, Long Long, Yibo Wang, Hongyu Chen, Kanbin Wang, Zhongxiang Wang, Jinwu Bai, Deting Xue, Zhijun Pan
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引用次数: 0

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.

Abstract Image

KDELR2通过GSK3β/β-catenin信号通路促进骨髓间充质干细胞成骨分化。
对于外科医生来说,骨折不愈合是一种具有挑战性的并发症。最近发现 Lys-Asp-Glu-Leu (KDEL) 内质网蛋白保留受体 2 (KDELR2) 与成骨不全症有关。然而,其确切机制仍不清楚。本研究利用慢病毒感染和小鼠骨折模型研究了KDELR2在成骨过程中的作用。结果表明,KDELR2敲除会抑制mBMSCs的成骨分化,而KDELR2过表达则有相反的作用。此外,KDELR2过表达会上调活性-β-catenin和磷酸化-GSK3β(Ser9)的水平,而KDELR2敲除会下调活性-β-catenin和磷酸化-GSK3β(Ser9)的水平。在骨折模型中,过表达 KDELR2 的 mBMSCs 可促进骨折愈合。总之,KDELR2通过调节GSK3β/β-catenin信号通路促进mBMSCs成骨。
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来源期刊
Cell and Tissue Research
Cell and Tissue Research 生物-细胞生物学
CiteScore
7.00
自引率
2.80%
发文量
142
审稿时长
1 months
期刊介绍: The journal publishes regular articles and reviews in the areas of molecular, cell, and supracellular biology. In particular, the journal intends to provide a forum for publishing data that analyze the supracellular, integrative actions of gene products and their impact on the formation of tissue structure and function. Submission of papers with an emphasis on structure-function relationships as revealed by recombinant molecular technologies is especially encouraged. Areas of research with a long-standing tradition of publishing in Cell & Tissue Research include: - neurobiology - neuroendocrinology - endocrinology - reproductive biology - skeletal and immune systems - development - stem cells - muscle biology.
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