Evidences for a new role of miR-214 in chondrogenesis

• Autor(a) principal: Roberto, Vania Palma
• Data de Publicação: 2018
• Outros Autores: Gavaia, Paulo, Nunes, Maria Joao, Rodrigues, Elsa, M. Leonor Cancela, Tiago, Daniel
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/11329
• topic: Zebrafish Danio-Rerio; Matrix gla protein; Cranial neural crest; Skeletal development; Bone-formation; Osteoblast differentiation; Gene-expression; Osteogenic Differentiation; Gilthead seabream; Cell lineage

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.