Centre of Marine Sciences (CCMAR/CIMAR-LA), University of Algarve, 8005-139, Faro, Portugal.
PhD Program in Biomedical Sciences, DCBM, University of Algarve, 8005-139, Faro, Portugal.
Sci Rep. 2018 Feb 27;8(1):3704. doi: 10.1038/s41598-018-21735-w.
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.
miR-214 通过抑制成骨作用和刺激破骨细胞生成而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其在软骨发生中的可能作用仍不清楚。在这里，我们表明 miR-214 的表达在斑马鱼骨骼的骨和软骨中被检测到，并在鼠 ATDC5 软骨细胞分化期间下调。此外，我们观察到 miR-214 初级转录物 Dnm3os 的转录调控在脊椎动物中是保守的，在 ATDC5 软骨细胞中受 Ets1 调控。此外，miR-214 的过表达在体外和体内减轻了软骨细胞分化，可能通过靶向激活转录因子 4（Atf4）。事实上，miR-214 在体内的过表达阻碍了斑马鱼头骨软骨的形成，并与 atf4 以及关键的软骨发生因子 sox9 和 col2a1 的下调相一致。我们表明，miR-214 的过表达通过可能通过保守机制影响软骨细胞分化而在软骨发生中发挥负作用。
