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J Cell Physiol：Lgr4的缺失可抑制骨间充质干细胞的分化，迁移和凋亡，并促进其增殖

2019-02-07 MedSci MedSci原创

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调节骨髓间充质干细胞（BMSCs）的关键信号传导网络目前尚未不明确。Lgr4属于富含亮氨酸重复序列的G蛋白偶联受体（LGR）家族，在早期胚胎发育到成年期的多种组织中广泛表达。我们使用插入Lgr4基因的β-geo基因捕获小鼠研究了Lgr4在BMSCs以及成骨，脂肪生成和骨骼肌成肌细胞中是否起作用。通过β-gal染色，在E16.5的Lgr4 +/-小鼠的骨骼，脂肪和肌肉组织中检测到Lgr4的大量表达，

调节骨髓间充质干细胞（BMSCs）的关键信号传导网络目前尚未不明确。Lgr4属于富含亮氨酸重复序列的G蛋白偶联受体（LGR）家族，在早期胚胎发育到成年期的多种组织中广泛表达。我们使用插入Lgr4基因的β-geo基因捕获小鼠研究了Lgr4在BMSCs以及成骨，脂肪生成和骨骼肌成肌细胞中是否起作用。

通过β-gal染色，在E16.5的Lgr4 +/-小鼠的骨骼，脂肪和肌肉组织中检测到Lgr4的大量表达，且集落形成单位-成纤维细胞测定显示Lgr4缺陷促进BMSCs的增殖（野生型[WT]为16±4和Lgr4-/-为28±2），transwell迁移测定显示抑制BMSCs迁移（WT为103±18，Lgr4-/-为57±10），膜联蛋白V染色试验显示凋亡率为0.0720±0.0123到0.0189±0.0051。敲除Lgr4通过抑制BMSC向成骨细胞或脂肪细胞的分化而使骨量和脂肪量减少（BV/TV从WT小鼠中的19.16±2.14增加至KO小鼠的10.36±1.96）。此外，LGR4调节成骨，脂肪形成和肌源性基因表达。重要的是，我们的数据显示，敲除Lgr4通过抑制成骨细胞分化来抑制骨折愈合。此外，BMSCs中Lgr4的缺失延迟了BMSCs移植后干细胞治疗后的骨折愈合。

总之，该研究结果表明，LGR4对于中胚层衍生的组织发育和BMSCs分化至关重要，这表明LGR4可能是相关疾病的有希望的药物靶标和干细胞治疗的关键蛋白质。

原始出处：

Sun P, Jia K, et al., Loss of Lgr4 inhibits differentiation, migration and apoptosis, and promotes proliferation in bone mesenchymal stem cells. J Cell Physiol. 2018 Dec 7. doi: 10.1002/jcp.27927.

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    2019-04-20 cmj8wellington

    #Physio#

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    2019-11-29 zhaozhouchifen

    #Cell#

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    2019-04-03 ms8888626721583891

    #迁移#

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    2019-03-10 h.y200607_23674418

    #间充质干细#

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    2019-03-24 维他命

    #CEL#

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