title: MicroRNA-34a regulates migration of chondroblast and IL-1β-induced degeneration of chondrocytes by targeting EphA5.
abstract: MicroRNAs function as an endogenous mode of fine gene regulation and have been implicated in multiple differentiation and developmental processes. In the present study, we investigated the role of miRNA-34 during chondrogenic differentiation of chick limb mesenchymal cells. We found that the expression of miR-34a increased upon chondrogenic inhibition. Blockade of miR-34a via PNA-based antisense oligonucleotides (ASOs) recovered the chondro-inhibitory actions of JNK inhibitor on migration of chondrogenic progenitors and the formation of precartilage condensation. Furthermore, we determined that EphA5 is a relevant target of miR-34a during chondrogenesis. MiR-34a was necessary and sufficient to down-regulate EphA5 expression, and up-modulation of EphA5 is sufficient to overcome inhibitory actions of miR-34 inhibition on cell migration and condensation of chick limb mesenchymal cells on collagen substrate. Taken together, our data suggest that miR-34a is a negative modulator of chondrogenesis, particularly in migration of chondroblasts, by targeting EphA5 and resulting inhibition of cellular condensation during chondrogenesis of chick limb mesenchymal cells.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Wonkwang University, Iksan, Chunbuk 570-749, Republic of Korea.
authors.forename: Dongkyun
authors.initials: D
authors.lastname: Kim
authors.forename: Jinsoo
authors.initials: J
authors.lastname: Song
authors.forename: Sunhyo
authors.initials: S
authors.lastname: Kim
authors.forename: Churl-Hong
authors.initials: CH
authors.lastname: Chun
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Jin
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D002645:Chickens; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D020219:Chondrogenesis; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology; D035683:MicroRNAs / Q000378:metabolism*; D051381:Rats; D036123:Receptor, EphA5 / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D036123:Receptor, EphA5; D048670:MAP Kinase Kinase 4