Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone

Supaporn Suttamanatwong, Eric D Jensen, Jody Schilling, Renny T. Franceschi, Ann E. Carlson, Kim Mansky, Rajaram Gopalakrishnan

Research output: Contribution to journalArticle

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Abstract

As part of its catabolic action in bone, parathyroid hormone (PTH) inhibits extracellular matrix mineralization. We previously showed that PTH dose-dependently induces matrix gla protein (MGP) expression in osteoblasts and this induction is at least partially responsible for PTH-mediated inhibition of mineralization. Recently, we identified PKA and ERK/MAPK as the key signaling pathways involved in PTH regulation of MGP expression. The goal of this study was to further characterize the mechanism by which PTH stimulates expression of MGP. Deletion analysis of the murine Mgp gene promoter identified a PTH-responsive region between -173 bp and -49 bp. Using gel-mobility shift assays we found that Sp1/Sp3, and Runx2 bind to distinct sites within this region. Mutation of either the Sp or the Runx2 site reduced MGP induction by PTH, while mutation of both sites completely abolished PTH responsiveness. Overexpression of Runx2 or Sp1 activated the Mgp reporter, while Sp3 was a dose-dependent repressor of Sp1 and PTH-induced MGP expression. Collectively, these data show that PTH regulates MGP gene transcription in osteoblasts through altered activities of Sp and Runx2 transcription factors.

Original languageEnglish (US)
Pages (from-to)284-292
Number of pages9
JournalJournal of Cellular Biochemistry
Volume107
Issue number2
DOIs
StatePublished - May 15 2009

Fingerprint

Core Binding Factor Alpha 1 Subunit
Parathyroid Hormone
Osteoblasts
Sp Transcription Factors
Genes
matrix Gla protein
Mutation
Electrophoretic Mobility Shift Assay
Transcription
Extracellular Matrix

Keywords

  • Matrix gla protein
  • Osteoblasts
  • Parathyroid hormone
  • Runx2
  • Sp transcription factors

Cite this

Suttamanatwong, S., Jensen, E. D., Schilling, J., Franceschi, R. T., Carlson, A. E., Mansky, K., & Gopalakrishnan, R. (2009). Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone. Journal of Cellular Biochemistry, 107(2), 284-292. https://doi.org/10.1002/jcb.22124

Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone. / Suttamanatwong, Supaporn; Jensen, Eric D; Schilling, Jody; Franceschi, Renny T.; Carlson, Ann E.; Mansky, Kim; Gopalakrishnan, Rajaram.

In: Journal of Cellular Biochemistry, Vol. 107, No. 2, 15.05.2009, p. 284-292.

Research output: Contribution to journalArticle

Suttamanatwong, S, Jensen, ED, Schilling, J, Franceschi, RT, Carlson, AE, Mansky, K & Gopalakrishnan, R 2009, 'Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone', Journal of Cellular Biochemistry, vol. 107, no. 2, pp. 284-292. https://doi.org/10.1002/jcb.22124
Suttamanatwong S, Jensen ED, Schilling J, Franceschi RT, Carlson AE, Mansky K et al. Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone. Journal of Cellular Biochemistry. 2009 May 15;107(2):284-292. https://doi.org/10.1002/jcb.22124
Suttamanatwong, Supaporn ; Jensen, Eric D ; Schilling, Jody ; Franceschi, Renny T. ; Carlson, Ann E. ; Mansky, Kim ; Gopalakrishnan, Rajaram. / Sp proteins and Runx2 mediate regulation of matrix gla protein (MGP) expression by parathyroid hormone. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 2. pp. 284-292.
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