miR-27 regulates chondrogenesis by suppressing focal adhesion kinase during pharyngeal arch development.
miR-27 regulates chondrogenesis by suppressing focal adhesion kinase during pharyngeal arch development.
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DOI：
10.1016/j.ydbio.2017.06.013
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发表时间：
2017-09-01
影响因子：
2.7
通讯作者：
Patton JG
中科院分区：
文献类型：
--
作者：
Kara N;Wei C;Commanday AC;Patton JG
颅神经嵴细胞是一种多能细胞群，产生咽软骨的所有成分，并分化为软骨细胞，受到时间细胞内和细胞外信号的严格调节。在这里，我们证明了miR-27作为软骨形成的积极调节因子的新作用，miR-27是咽弓中高度富集的microRNA。miR-27的敲低通过减弱增殖和阻断软骨前细胞的分化导致咽软骨几乎完全丧失。Focal adhesion kinase （FAK）是整合素介导的细胞外基质（ECM）粘附的关键调节因子，并被认为是软骨形成的负调节因子。我们发现FAK在软骨形成过程中在咽弓中下调，是miR-27的直接靶点。抑制miR-27突变体中FAK的积累部分挽救了miR-27敲低后观察到的严重咽软骨缺损。这些数据支持miR-27通过调节FAK促进咽弓软骨分化的关键作用。
Cranial neural crest cells are a multipotent cell population that generate all the elements of the pharyngeal cartilage with differentiation into chondrocytes tightly regulated by temporal intracellular and extracellular cues. Here, we demonstrate a novel role for miR-27, a highly enriched microRNA in the pharyngeal arches, as a positive regulator of chondrogenesis. Knock down of miR-27 led to nearly complete loss of pharyngeal cartilage by attenuating proliferation and blocking differentiation of pre-chondrogenic cells. Focal adhesion kinase (FAK) is a key regulator in integrin-mediated extracellular matrix (ECM) adhesion and has been proposed to function as a negative regulator of chondrogenesis. We show that FAK is downregulated in the pharyngeal arches during chondrogenesis and is a direct target of miR-27. Suppressing the accumulation of FAK in miR-27 morphants partially rescued the severe pharyngeal cartilage defects observed upon knock down of miR-27. These data support a crucial role for miR-27 in promoting chondrogenic differentiation in the pharyngeal arches through regulation of FAK.
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