巨噬细胞清道夫受体1通过JAK/STAT3信号通路调节骨髓间充质干细胞成骨分化
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国家自然科学基金(81472081); 国家自然科学基金青年基金(81100942);江苏省自然科学基金(BK2010539);2020年江苏省青蓝工程资助


Macrophage scavenger receptor 1 regulates BMSC osteogenic differentiation through JAK/STAT3 signaling pathway
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    摘要:

    目的:探索巨噬细胞清道夫受体1(macrophage scavenger receptor 1,MSR1)对骨髓间充质干细胞(bone marrow mesenchymal stem cell,BMSC)成骨分化的调控作用及机制。方法:在体内水平,对MSR1 野生型(wild type,WT)及敲除(knock out,KO)小鼠进行胫骨骨皮质缺损模型,并于术后第10天对缺损部位进行小动物CT扫描三维重建及参数分析。在体外实验中,用MSR1 WT及KO小鼠来源的原代巨噬细胞的条件培养基刺激BMSC,并通过CCK-8、Transwell、茜素红染色、碱性磷酸酶染色和实时定量逆转录聚合酶链反应等实验检测MSR1对BMSC的增殖、迁移和成骨分化能力的调控作用。最后,通过Western blot和ELISA实验探讨MSR1对BMSC成骨分化发挥调控作用的具体机制。结果:在体内水平,MSR1的缺失可导致小鼠骨愈合能力显著减弱。在体外水平,MSR1的敲除可显著影响BMSC的成骨分化能力,但不影响增殖及迁移能力。在机制探索方面,MSR1可通过JAK/STAT3信号通路上调骨形态发生蛋白2(bone morphogenetic protein 2,BMP2)的分泌,进而发挥其对BMSC成骨分化的调控作用。结论:MSR1是巨噬细胞发挥调节BMSC成骨分化作用的关键分子之一,这为今后靶向MSR1促进骨愈合提供了坚实的理论基础。

    Abstract:

    Objective:To explore the effect and mechanism of macrophage scavenger receptor 1(MSR1)on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs). Methods:In vivo,MSR1 wild type(WT)and knock out(KO)mice were used to perform tibial monocortical defect model. Further,the three-dimensional reconstruction and parameter analysis after micro-CT scan were carried out on day 10 post-injury. In vitro,BMSCs were first stimulated by conditioned medium from MSR1 WT or KO primary macrophages. Then,CCK-8,Transwell,alizarin red staining,alkaline phosphatase staining and real-time quantitative reverse transcription polymerase chain reaction were performed to explore the effect of MSR1 on proliferation,migration and osteogenic differentiation of BMSCs. Western blot and ELISA were used to investigate the specific mechanism of MSR1 on osteogenic differentiation of BMSCs. Results:The loss of MSR1 significantly reduced the ability of bone regeneration in vivo. In addition,knockout of MSR1 in macrophages significantly affected the osteogenic differentiation ability of BMSCs,but not the proliferation and migration ability in vitro. We also identified MSR1 could increase the secretion of bone morphogenetic protein 2(BMP2)through JAK/STAT3 signaling pathway,thus exerting its regulatory effect on BMSCs osteogenic differentiation. Conclusion:MSR1 is one of the key molecules that macrophages play a role in regulating osteogenic differentiation of BMSCs,which provides a solid theoretical basis for targeting macrophages MSR1 to promote bone healing in the future.

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殷旻皓,刘 浩,张永杰.巨噬细胞清道夫受体1通过JAK/STAT3信号通路调节骨髓间充质干细胞成骨分化[J].南京医科大学学报(自然科学版),2020,(8):1105-1110

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  • 收稿日期:2020-04-26
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  • 在线发布日期: 2020-08-21
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