Control of mesenchymal lineage progression by microRNAs targeting the skeletal gene regulators Trps1 and Runx2
Department of Cell Biology
Medical Subject Headings
MicroRNAs; Osteoblasts; Chondrocytes; DNA-Binding Proteins; Transcription Factors; Core Binding Factor Alpha 1 Subunit; Mesenchymal Stem Cells; Musculoskeletal Development
Multiple microRNAs (miRNAs) that target the osteogenic Runt-related transcription factor 2 (RUNX2) define an interrelated network of miRNAs that control osteoblastogenesis. We addressed whether these miRNAs have functional targets beyond RUNX2 that co-regulate skeletal development. Here, we find that seven RUNX2-targeting miRNAs (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-205 and miR-217) also regulate the chondrogenic GATA transcription factor Tricho-Rhino-Phalangeal Syndrome I (TRPS1). While the efficacy of each miRNA to target RUNX2 or TRPS1 differs in osteoblasts and chondrocytes, each effectively blocks maturation of pre-committed osteoblasts and chondrocytes. Furthermore, these miRNAs can redirect mesenchymal stem cells into adipogenic cell fate with concomitant up-regulation of key lineage specific transcription factors. Thus, a program of multiple miRNAs controls mesenchymal lineage progression by selectively blocking differentiation of osteoblasts and chondrocytes to control skeletal development.
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Citation: J Biol Chem. 2012 Apr 27. [Epub ahead of print] doi:10.1074/jbc.M112.340398