MicroRNA-375, a new regulator of cadherin-7, suppresses the migration of chondrogenic progenitors

Endochondral bone formation requires a complex interplay among immature mesenchymal progenitor cells to form the cartilaginous anlagen, involving migration, aggregation and condensation. Even though condensation of chondrogenic progenitors is an essential step in this process, the mechanism(s) by which this occurs has not been well studied. Here, we investigated the involvement of microRNAs (miRNAs) in this process and found that the expression of miR-375 decreased upon chondrogenic differentiation of limb mesenchymal cells. Blockade of miR-375 via peptide nucleic acid (PNA)-based antisense oligonucleotides (ASOs) increased the migration of chondrogenic progenitors, the formation of precartilage condensations and the expression level of cadherin-7. Furthermore, miR-375 was necessary and sufficient to down-regulate cell migration through negative regulation of cadherin-7 by the direct interaction with 3' UTR of cadherin-7. In addition, miR-375 is also involved in the cell migration and precartilage condensation mediated by p38MAPK, a positive signaling in the chondrogenic differentiation. Collectively, our results suggest that miR-375 negatively modulates cell migration and subsequent precartilage condensation by targeting cadherin-7. (C) 2012 Elsevier Inc. All rights reserved.