Evidences for a new role of miR-214 in chondrogenesis

Roberto, Vania Palma; Gavaia, Paulo; Nunes, Maria Joao; Rodrigues, Elsa; M. Leonor Cancela; Tiago, Daniel

http://hdl.handle.net/10400.1/11329

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Abstract(s)

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.

Keywords

Zebrafish Danio-Rerio Matrix gla protein Cranial neural crest Skeletal development Bone-formation Osteoblast differentiation Gene-expression Osteogenic Differentiation Gilthead seabream Cell lineage