Abstract
MicroRNAs (miRNAs) have been implicated in various cellular processes, such as cell fate determination, cell death, and tumorigenesis. In the present study, we investigated the role of miRNA-34a (miR-34a) in the reorganization of the actin cytoskeleton, which is essential for chondrocyte differentiation. miRNA arrays to identify genes that appeared to be up-regulated or down-regulated during chondrogenesis were applied with chondrogenic progenitors treated with JNK inhibitor. PNA-based antisense oligonucleotides and miRNA precursor were used for investigation of the functional roles of miR-34a. We found that, in chick chondroprogenitors treated with JNK inhibitor, which suppresses chondrogenic differentiation, the expression levels of miR-34a and RhoA1 are up-regulated through modulation of Rac1 expression. Blockade of miR-34a via the use of PNA-based antisense oligonucleotides was associated with decreased protein expression of RhoA (a known modulator of stress fiber expression), down-regulation of stress fibers, up-regulation of Rac1, and recovery of protein level of type II collagen. miR-34a regulates RhoA/Rac1 cross-talk and negatively modulates reorganization of the actin cytoskeleton, which is one of the essential processes for establishing chondrocyte-specific morphology.
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