Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2

Ying Zhang, Rong Lin Xie, Jonathan Gordon, Kimberly LeBlanc, Janet L. Stein, Jane B. Lian, Andre J van Wijnen, Gary S. Stein

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)21926-21935
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number26
DOIs
StatePublished - Jun 22 2012
Externally publishedYes

Fingerprint

Gene Targeting
Regulator Genes
MicroRNAs
Genes
Osteoblasts
Chondrocytes
Transcription Factors
GATA Transcription Factors
Stem cells
Mesenchymal Stromal Cells
Up-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Zhang, Y., Xie, R. L., Gordon, J., LeBlanc, K., Stein, J. L., Lian, J. B., ... Stein, G. S. (2012). Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. Journal of Biological Chemistry, 287(26), 21926-21935. https://doi.org/10.1074/jbc.M112.340398

Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. / Zhang, Ying; Xie, Rong Lin; Gordon, Jonathan; LeBlanc, Kimberly; Stein, Janet L.; Lian, Jane B.; van Wijnen, Andre J; Stein, Gary S.

In: Journal of Biological Chemistry, Vol. 287, No. 26, 22.06.2012, p. 21926-21935.

Research output: Contribution to journalArticle

Zhang, Y, Xie, RL, Gordon, J, LeBlanc, K, Stein, JL, Lian, JB, van Wijnen, AJ & Stein, GS 2012, 'Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2', Journal of Biological Chemistry, vol. 287, no. 26, pp. 21926-21935. https://doi.org/10.1074/jbc.M112.340398
Zhang, Ying ; Xie, Rong Lin ; Gordon, Jonathan ; LeBlanc, Kimberly ; Stein, Janet L. ; Lian, Jane B. ; van Wijnen, Andre J ; Stein, Gary S. / Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 26. pp. 21926-21935.
@article{c525c47119d14a059455584968854c31,
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.",
author = "Ying Zhang and Xie, {Rong Lin} and Jonathan Gordon and Kimberly LeBlanc and Stein, {Janet L.} and Lian, {Jane B.} and {van Wijnen}, {Andre J} and Stein, {Gary S.}",
year = "2012",
month = "6",
day = "22",
doi = "10.1074/jbc.M112.340398",
language = "English (US)",
volume = "287",
pages = "21926--21935",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "26",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84862699407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862699407&partnerID=8YFLogxK

U2 - 10.1074/jbc.M112.340398

DO - 10.1074/jbc.M112.340398

M3 - Article

C2 - 22544738

AN - SCOPUS:84862699407

VL - 287

SP - 21926

EP - 21935

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 26

ER -