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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

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
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    2018-10-07 zhaojie88
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    2018-10-07 lq1771
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