Control of mesenchymal lineage progression by microRNAs targeting the skeletal gene regulators Trps1 and Runx2
Department of Cell Biology
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.
DOI of Published Version
J Biol Chem. 2012 Apr 27. [Epub ahead of print] doi:10.1074/jbc.M112.340398
The Journal of biological chemistry
Zhang Y, Xie R, Gordon JA, LeBlanc KT, Stein JL, Lian JB, Van Wijnen AJ, Stein GS. (2012). Control of mesenchymal lineage progression by microRNAs targeting the skeletal gene regulators Trps1 and Runx2. Stein, Stein, Lian, vanWijnen Lab Publications. https://doi.org/10.1074/jbc.M112.340398. Retrieved from https://escholarship.umassmed.edu/stein/257