p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation

Eric D. Jensen, Lingling Niu, Giuseppina Caretti, Samantha M. Nicol, Nadiya Teplyuk, Gary S. Stein, Vittorio Sartorelli, Andre J van Wijnen, Frances V. Fuller-Pace, Jennifer J Westendorf

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.

Original languageEnglish (US)
Pages (from-to)1438-1451
Number of pages14
JournalJournal of Cellular Biochemistry
Volume103
Issue number5
DOIs
StatePublished - Apr 1 2008

Fingerprint

Osteoblasts
DEAD-box RNA Helicases
Stem Cells
Transcription
Core Binding Factor Alpha 1 Subunit
Transcription Factors
Crosstalk
Gene expression
Proteomics
Purification
Assays
Proteins
Chemical activation
Cells
RNA
Specifications
Gene Expression
Cell Line

Keywords

  • CBFa1
  • Ddx5
  • DEAD box
  • Mesodermal cell differentiation
  • Osteocalcin

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Jensen, E. D., Niu, L., Caretti, G., Nicol, S. M., Teplyuk, N., Stein, G. S., ... Westendorf, J. J. (2008). p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. Journal of Cellular Biochemistry, 103(5), 1438-1451. https://doi.org/10.1002/jcb.21526

p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. / Jensen, Eric D.; Niu, Lingling; Caretti, Giuseppina; Nicol, Samantha M.; Teplyuk, Nadiya; Stein, Gary S.; Sartorelli, Vittorio; van Wijnen, Andre J; Fuller-Pace, Frances V.; Westendorf, Jennifer J.

In: Journal of Cellular Biochemistry, Vol. 103, No. 5, 01.04.2008, p. 1438-1451.

Research output: Contribution to journalArticle

Jensen, ED, Niu, L, Caretti, G, Nicol, SM, Teplyuk, N, Stein, GS, Sartorelli, V, van Wijnen, AJ, Fuller-Pace, FV & Westendorf, JJ 2008, 'p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation', Journal of Cellular Biochemistry, vol. 103, no. 5, pp. 1438-1451. https://doi.org/10.1002/jcb.21526
Jensen ED, Niu L, Caretti G, Nicol SM, Teplyuk N, Stein GS et al. p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. Journal of Cellular Biochemistry. 2008 Apr 1;103(5):1438-1451. https://doi.org/10.1002/jcb.21526
Jensen, Eric D. ; Niu, Lingling ; Caretti, Giuseppina ; Nicol, Samantha M. ; Teplyuk, Nadiya ; Stein, Gary S. ; Sartorelli, Vittorio ; van Wijnen, Andre J ; Fuller-Pace, Frances V. ; Westendorf, Jennifer J. / p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. In: Journal of Cellular Biochemistry. 2008 ; Vol. 103, No. 5. pp. 1438-1451.
@article{d68fa2f9653f4918a6011bfee8a539a0,
title = "p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation",
abstract = "Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.",
keywords = "CBFa1, Ddx5, DEAD box, Mesodermal cell differentiation, Osteocalcin",
author = "Jensen, {Eric D.} and Lingling Niu and Giuseppina Caretti and Nicol, {Samantha M.} and Nadiya Teplyuk and Stein, {Gary S.} and Vittorio Sartorelli and {van Wijnen}, {Andre J} and Fuller-Pace, {Frances V.} and Westendorf, {Jennifer J}",
year = "2008",
month = "4",
day = "1",
doi = "10.1002/jcb.21526",
language = "English (US)",
volume = "103",
pages = "1438--1451",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation

AU - Jensen, Eric D.

AU - Niu, Lingling

AU - Caretti, Giuseppina

AU - Nicol, Samantha M.

AU - Teplyuk, Nadiya

AU - Stein, Gary S.

AU - Sartorelli, Vittorio

AU - van Wijnen, Andre J

AU - Fuller-Pace, Frances V.

AU - Westendorf, Jennifer J

PY - 2008/4/1

Y1 - 2008/4/1

N2 - Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.

AB - Runx2 is an essential transcription factor for osteoblast development from mesenchymal progenitors. Runx2 regulates gene expression by interacting with numerous transcription factors and co-activators to integrate signaling events within the nucleus. In this study we used affinity purification and proteomic techniques to identify novel Runx2 interacting proteins. One of these proteins is the DEAD box RNA helicase, p68 (Ddx5). p68 regulates many aspects of RNA expression, including transcription and splicing. p68 co-localized with Runx2 in punctate foci within the nucleus. In transcription assays, p68 functioned as a co-activator of Runx2, but its helicase activity was not essential for co-activation. In accordance, Runx2 transcriptional activity was muted in p68-suppressed cells. Surprisingly, osteoblast differentiation of the multipotent progenitor C2C12 cell line was accelerated by p68 suppression and Runx2 suppressed p68 expression in calvarial progenitor cells. Together these data demonstrate that p68 is a novel co-activator for Runx2, but it inhibits osteogenic differentiation of progenitor cells. Moreover Runx2 has an active role in regulating p68 levels in osteoblast precursors. Thus, crosstalk between Runx2 and p68 controls osteoblast specification and maturation at multiple levels.

KW - CBFa1

KW - Ddx5

KW - DEAD box

KW - Mesodermal cell differentiation

KW - Osteocalcin

UR - http://www.scopus.com/inward/record.url?scp=41749105770&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41749105770&partnerID=8YFLogxK

U2 - 10.1002/jcb.21526

DO - 10.1002/jcb.21526

M3 - Article

C2 - 17960593

AN - SCOPUS:41749105770

VL - 103

SP - 1438

EP - 1451

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 5

ER -