Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells

Kanagaraj Gomathi, Muthukumar Rohini, Nicola C. Partridge, Nagarajan Selvamurugan

Research output: Contribution to journalArticlepeer-review

Abstract

Transforming growth factor beta 1 (TGF-β1) functions as a coupling factor between bone development and resorption. Matrix metalloproteinase 13 (MMP13) is important in bone remodeling, and skeletal dysplasia is caused by a deficiency in MMP13 expre-ssion. Runx2, a transcription factor is essential for bone development, and MMP13 is one of its target genes. TGF-β1 promoted Runx2 phosphorylation, which was necessary for MMP13 production in osteoblastic cells, as we previously shown. Since the phosphorylation of some proteins causes them to be degraded by the ubiquitin/proteasome pathway, we hypothesized that TGF-β1 might stabilize the phosphorylated Runx2 protein for its activity by other post-translational modification (PTM). This study demonstrated that TGF-β1-stimulated Runx2 acetylation in rat osteoblastic cells. p300, a histone acetyltransferase interacted with Runx2, and it promoted Runx2 acetylation upon TGF-β1-treatment in these cells. Knockdown of p300 decreased the TGF-β1-stimulated Runx2 acetylation and MMP13 expression in rat osteoblastic cells. TGF-β1-treatment stimulated the acetylated Runx2 bound at the MMP13 promoter, and knockdown of p300 reduced this effect in these cells. Overall, our studies identified the transcriptional regulation of MMP13 by TGF-β1 via Runx2 acetylation in rat osteoblastic cells, and these findings contribute to the knowledge of events presiding bone metabolism.

Original languageEnglish (US)
Article number0292
JournalBiological Chemistry
DOIs
StateAccepted/In press - 2021

Keywords

  • acetylation
  • matrix metalloproteinase 13 (MMP13)
  • Runx2
  • transforming growth factor beta 1 (TGF-β1)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Clinical Biochemistry

Fingerprint

Dive into the research topics of 'Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells'. Together they form a unique fingerprint.

Cite this