Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
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.
Funding source: Science and Engineering Research Board
Award Identifier / Grant number: CRG/2018/000051
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: A grant from India’s Department of Science and Technology-Science and Engineering Research Board (DST-SERB) sponsored this research (CRG/2018/000051 to N.S.).
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Conflict of interest statement: The authors declare no conflicts of interest regarding this manuscript.
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Artikel in diesem Heft
- Frontmatter
- Research Articles
- Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
- Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
- High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis
- Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
- Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
- M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
- Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
- Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells
Artikel in diesem Heft
- Frontmatter
- Research Articles
- Inhibitory effect of mitoquinone against the α-synuclein fibrillation and relevant neurotoxicity: possible role in inhibition of Parkinson’s disease
- Effect of myeloperoxidase oxidation and N-homocysteinylation of high-density lipoprotein on endothelial repair function
- High cellulose diet promotes intestinal motility through regulating intestinal immune homeostasis and serotonin biosynthesis
- Quercetin increases mitochondrial proteins (VDAC and SDH) and downmodulates AXL and PIM-1 tyrosine kinase receptors in NRAS melanoma cells
- Regulation of transforming growth factor-β1-stimulation of Runx2 acetylation for matrix metalloproteinase 13 expression in osteoblastic cells
- M6A methylation-mediated elevation of SM22α inhibits the proliferation and migration of vascular smooth muscle cells and ameliorates intimal hyperplasia in type 2 diabetes mellitus
- Characterization of hepatic zonation in mice by mass-spectrometric and antibody-based proteomics approaches
- Characterization of a fluorescent 1,8-naphthalimide-functionalized PAMAM dendrimer and its Cu(ii) complexes as cytotoxic drugs: EPR and biological studies in myeloid tumor cells