Evidences for a New Role of miR-214 in Chondrogenesis.
Evidences for a New Role of miR-214 in Chondrogenesis.
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DOI：
10.1038/s41598-018-21735-w
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发表时间：
2018-02-27
影响因子：
4.6
通讯作者：
Tiago DM
中科院分区：
文献类型：
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作者：
Roberto VP;Gavaia P;Nunes MJ;Rodrigues E;Cancela ML;Tiago DM
已知miR-214通过抑制骨生成和刺激破骨细胞生成在哺乳动物骨骼发育中发挥作用，但关于其他脊椎动物的数据以及在软骨形成中的可能作用仍然未知。在这里，我们发现miR-214的表达在斑马鱼骨骼的骨和软骨中检测到，并且在小鼠ATDC 5软骨细胞分化过程中下调。此外，我们观察到在脊椎动物中miR-214初级转录本Dnm 3 os的转录调控保守，在ATDC 5软骨形成细胞中受到Ets 1的调控。此外，在体外和体内过表达miR-214可能通过靶向激活转录因子4（Atf 4）来减轻软骨细胞分化。事实上，体内miR-214过表达阻碍了斑马鱼颅软骨的形成，并与atf 4和关键软骨形成参与者sox 9和col 2a 1的下调相一致。我们发现miR-214过表达可能通过保守机制影响软骨细胞分化，从而在软骨形成中发挥负面作用。
miR-214 is known to play a role in mammalian skeletal development through inhibition of osteogenesis and stimulation of osteoclastogenesis, but data regarding other vertebrates, as well as a possible role in chondrogenesis, remain unknown. Here, we show that miR-214 expression is detected in bone and cartilage of zebrafish skeleton, and is downregulated during murine ATDC5 chondrocyte differentiation. Additionally, we observed a conservation of the transcriptional regulation of miR-214 primary transcript Dnm3os in vertebrates, being regulated by Ets1 in ATDC5 chondrogenic cells. Moreover, overexpression of miR-214 in vitro and in vivo mitigated chondrocyte differentiation probably by targeting activating transcription factor 4 (Atf4). Indeed, miR-214 overexpression in vivo hampered cranial cartilage formation of zebrafish and coincided with downregulation of atf4 and of the key chondrogenic players sox9 and col2a1. We show that miR-214 overexpression exerts a negative role in chondrogenesis by impacting on chondrocyte differentiation possibly through conserved mechanisms.