title: Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2.
abstract: 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.
authors.affiliation: Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rong-Lin
authors.initials: RL
authors.lastname: Xie
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gordon
authors.forename: Kimberly
authors.initials: K
authors.lastname: LeBlanc
authors.forename: Janet L
authors.initials: JL
authors.lastname: Stein
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lian
authors.forename: Andre J
authors.initials: AJ
authors.lastname: van Wijnen
authors.forename: Gary S
authors.initials: GS
authors.lastname: Stein
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D019902:Chondrocytes / Q000166:cytology; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D035683:MicroRNAs / Q000378:metabolism; D008954:Models, Biological; D041681:NIH 3T3 Cells; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D050980:GATA Transcription Factors; D035683:MicroRNAs; D012097:Repressor Proteins; C493716:Runx2 protein, mouse; D014157:Transcription Factors; C525953:Trps1 protein, mouse