Dicer-dependent pathways regulate chondrocyte proliferation and differentiation

摘要: Small noncoding RNAs, microRNAs (miRNAs), bind to messenger RNAs through base pairing suppress gene expression. Despite accumulating evidence that miRNAs play critical roles in various biological processes across diverse organisms, their mammalian skeletal development have not been demonstrated. Here, we show Dicer, an essential component for biogenesis of miRNAs, is normal development. Dicer-null growth plates a progressive reduction the proliferating pool chondrocytes, leading severe defects and premature death mice. The chondrocytes caused by two distinct mechanisms: decreased chondrocyte proliferation accelerated differentiation into postmitotic hypertrophic chondrocytes. These appear be mechanisms downstream or independent Ihh-PTHrP signaling pathway, pivotal system regulates differentiation. Microarray analysis showed limited expression changes miRNA-target genes, suggesting that, majority cases, chondrocytic do directly regulate target RNA abundance. Our results demonstrate role Dicer-dependent pathway regulation during