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Front Physiol：FasL调节Mmp2在成骨细胞中的表达

2018-10-05 MedSci MedSci原创

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已知FasL是凋亡通路中的重要参与者，但最近的报道指出其在细胞死亡之外的重要新作用，如对骨细胞的作用。这得到了在成骨过程中FasL的非凋亡外观以及与FasL缺陷（gld）小鼠中的细胞凋亡无关的明显骨改变的支持。但是这一新角色背后的分子机制尚未揭示。 本研究中，研究人员探究了膜内骨，其中成骨细胞直接与间充质前体分化而没有中间软骨形成步骤。小鼠下颌第一臼齿周的颌骨作为研究模型。选择在发育期间首先

已知FasL是凋亡通路中的重要参与者，但最近的报道指出其在细胞死亡之外的重要新作用，如对骨细胞的作用。这得到了在成骨过程中FasL的非凋亡外观以及与FasL缺陷（gld）小鼠中的细胞凋亡无关的明显骨改变的支持。但是这一新角色背后的分子机制尚未揭示。

本研究中，研究人员探究了膜内骨，其中成骨细胞直接与间充质前体分化而没有中间软骨形成步骤。小鼠下颌第一臼齿周的颌骨作为研究模型。选择在发育期间首先存在复杂的一组骨细胞（成骨细胞、骨细胞、破骨细胞）的阶段进行初步检查。

结果，免疫组织化学染色在此阶段检测非凋亡细胞中的FasL。此外，与野生型样品相比，成骨PCR阵列分析显示，FasL缺陷组在gld骨中Mmp2的表达显著降低。为了检查这种新型FasL-Mmp2关系的可能性，使用抗FasL抗体或rmFasL处理膜内骨衍生的成骨细胞（MC3T3-E1）。实际上，FasL中和导致Mmp2的表达降低，并且添加到细胞中的rmFasL导致相反的效果。由于Mmp2-/- 小鼠显示膜内骨的年龄依赖性改变，因此检查了gld下颌骨的早期阶段，并且在gld小鼠中也证实了年龄依赖性表型。

总之，该研究体内和体外研究结果表明FasL在与Mmp2表达相关的骨发育中具有新的非凋亡功能。

原始出处：

Svandova E, Vesela B, et al., FasL Modulates Expression of Mmp2 in Osteoblasts. Front Physiol. 2018 Sep 19;9:1314. doi: 10.3389/fphys.2018.01314. eCollection 2018.

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    2019-03-08 gracezdd

    #FAS#

    0

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    2018-11-22 cmj8wellington

    #Physio#

    0

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    2018-10-07 zhaojie88

    #成骨#

    0

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    2018-10-07 jj000004

    #骨细胞#

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    2018-10-07 lq1771

    #ASL#

    0