TY - JOUR
T1 - Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2
AU - Zhang, Ying
AU - Xie, Rong Lin
AU - Gordon, Jonathan
AU - LeBlanc, Kimberly
AU - Stein, Janet L.
AU - Lian, Jane B.
AU - Van Wijnen, Andre J.
AU - Stein, Gary S.
PY - 2012/6/22
Y1 - 2012/6/22
N2 - 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 coregulate 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). Although the efficacy of each miRNA to target RUNX2 or TRPS1 differs in osteoblasts and chondrocytes, each effectively blocks maturation of precommitted 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.
AB - 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 coregulate 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). Although the efficacy of each miRNA to target RUNX2 or TRPS1 differs in osteoblasts and chondrocytes, each effectively blocks maturation of precommitted 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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U2 - 10.1074/jbc.M112.340398
DO - 10.1074/jbc.M112.340398
M3 - Article
C2 - 22544738
AN - SCOPUS:84862699407
SN - 0021-9258
VL - 287
SP - 21926
EP - 21935
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 26
ER -