Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors

Nadiya M. Teplyuk, Mario Galindo, Viktor I. Teplyuk, Jitesh Pratap, Daniel W. Young, David Lapointe, Amjad Javed, Janet L. Stein, Jane B. Lian, Gary S. Stein, Andre J van Wijnen

Research output: Contribution to journalArticle

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Abstract

Runt-related transcription factor 2 (Runx2) controls lineage commitment, proliferation, and anabolic functions of osteoblasts as the subnuclear effector of multiple signaling axes (e.g. transforming growth factor-β/BMP-SMAD, SRC/YES-YAP, and GROUCHO/TLE). Runx2 levels oscillate during the osteoblast cell cycle with maximal levels in G1. Here we examined what functions and target genes of Runx2 control osteoblast growth. Forced expression of wild type Runx2 suppresses growth of Runx2-/- osteoprogenitors. Point mutants defective for binding to WW domain or SMAD proteins or the nuclear matrix retain this growth regulatory ability. Hence, key signaling pathways are dispensable for growth control by Runx2. However, mutants defective for DNA binding or C-terminal gene repression/activation functions do not block proliferation. Target gene analysis by Affymetrix expression profiling shows that the C terminus of Runx2 regulates genes involved in G protein-coupled receptor signaling (e.g. Rgs2, Rgs4, Rgs5, Rgs16, Gpr23, Gpr30, Gpr54, Gpr64, and Gna13). We further examined the function of two genes linked to cAMP signaling as follows: Gpr30 that is stimulated and Rgs2 that is down-regulated by Runx2. RNA interference of Gpr30 and forced expression of Rgs2 in each case inhibit osteoblast proliferation. Notwithstanding its growth-suppressive potential, our results surprisingly indicate that Runx2 may sensitize cAMP-related G protein-coupled receptor signaling by activating Gpr30 and repressing Rgs2 gene expression in osteoblasts to increase responsiveness to mitogenic signals.

Original languageEnglish (US)
Pages (from-to)27585-27597
Number of pages13
JournalJournal of Biological Chemistry
Volume283
Issue number41
DOIs
StatePublished - Oct 10 2008
Externally publishedYes

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Osteoblasts
GTP-Binding Proteins
Genes
Growth
G-Protein-Coupled Receptors
Nuclear Matrix-Associated Proteins
Transforming Growth Factors
RNA Interference
Gene expression
Transcriptional Activation
Cell Cycle
Transcription Factors
Chemical activation
Cells
RNA
Gene Expression
DNA
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Teplyuk, N. M., Galindo, M., Teplyuk, V. I., Pratap, J., Young, D. W., Lapointe, D., ... van Wijnen, A. J. (2008). Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. Journal of Biological Chemistry, 283(41), 27585-27597. https://doi.org/10.1074/jbc.M802453200

Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. / Teplyuk, Nadiya M.; Galindo, Mario; Teplyuk, Viktor I.; Pratap, Jitesh; Young, Daniel W.; Lapointe, David; Javed, Amjad; Stein, Janet L.; Lian, Jane B.; Stein, Gary S.; van Wijnen, Andre J.

In: Journal of Biological Chemistry, Vol. 283, No. 41, 10.10.2008, p. 27585-27597.

Research output: Contribution to journalArticle

Teplyuk, NM, Galindo, M, Teplyuk, VI, Pratap, J, Young, DW, Lapointe, D, Javed, A, Stein, JL, Lian, JB, Stein, GS & van Wijnen, AJ 2008, 'Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors', Journal of Biological Chemistry, vol. 283, no. 41, pp. 27585-27597. https://doi.org/10.1074/jbc.M802453200
Teplyuk NM, Galindo M, Teplyuk VI, Pratap J, Young DW, Lapointe D et al. Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. Journal of Biological Chemistry. 2008 Oct 10;283(41):27585-27597. https://doi.org/10.1074/jbc.M802453200
Teplyuk, Nadiya M. ; Galindo, Mario ; Teplyuk, Viktor I. ; Pratap, Jitesh ; Young, Daniel W. ; Lapointe, David ; Javed, Amjad ; Stein, Janet L. ; Lian, Jane B. ; Stein, Gary S. ; van Wijnen, Andre J. / Runx2 regulates G protein-coupled signaling pathways to control growth of osteoblast progenitors. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 41. pp. 27585-27597.
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AU - Pratap, Jitesh

AU - Young, Daniel W.

AU - Lapointe, David

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