ArticleMolecular endocrinology (Baltimore, Md.)2009
Runx2 recruits p300 to mediate parathyroid hormone's effects on histone acetylation and transcriptional activation of the matrix metalloproteinase-13 gene.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- High levels of histone acetylation modifications promote the formation of PGCs.Poultry science · 2025Article
- Circ_ST6GAL1-mediated competing endogenous RNA network regulates TGF-β1-stimulated matrix Metalloproteinase-13 expression via Runx2 acetylation in osteoblasts.Non-coding RNA research · 2024Article
- Functional consequences of C-terminal mutations in RUNX2.Scientific reports · 2023Article
- TGFβ-mediated MMP13 secretion drives myoepithelial cell dependent breast cancer progression.NPJ breast cancer · 2023Article
- The role of Trithorax family regulating osteogenic and Chondrogenic differentiation in mesenchymal stem cells.Cell proliferation · 2022Review
- Role of Runx2 in prostate development and stem cell function.The Prostate · 2021Article
- Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2).Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Runx2 plays a central role in Osteoarthritis development.Journal of orthopaedic translation · 2020Review
- Bone Remodeling: Histone Modifications as Fate Determinants of Bone Cell Differentiation.International journal of molecular sciences · 2019Review
- The intracellular NADH level regulates atrophic nonunion pathogenesis through the CtBP2-p300-Runx2 transcriptional complex.International journal of biological sciences · 2018Article
- MEF2C Interacts With c-FOS in PTH-Stimulated Mmp13 Gene Expression in Osteoblastic Cells.Endocrinology · 2017Article
- MAP Kinase-Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic Modification of Chromatin During Osteoblast Differentiation.Journal of cellular physiology · 2017Article
- Control of the Osteoblast Lineage by Mitogen-Activated Protein Kinase Signaling.Current molecular biology reports · 2017Article
- Article
- PTH Signaling and Epigenetic Control of Bone Remodeling.Current molecular biology reports · 2016Article
- miRNA-132-3p inhibits osteoblast differentiation by targeting Ep300 in simulated microgravity.Scientific reports · 2015Article
- Sirtuin 1 is a negative regulator of parathyroid hormone stimulation of matrix metalloproteinase 13 expression in osteoblastic cells: role of sirtuin 1 in the action of PTH on osteoblasts.The Journal of biological chemistry · 2015Article
- A positive role of microRNA-15b on regulation of osteoblast differentiation.Journal of cellular physiology · 2014Article
- Histone H3 lysine 36 methyltransferase Whsc1 promotes the association of Runx2 and p300 in the activation of bone-related genes.PloS one · 2014Article
- Transcriptional regulatory cascades in Runx2-dependent bone development.Tissue engineering. Part B, Reviews · 2013Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
PTH regulates transcription of a number of genes involved in bone remodeling and calcium homeostasis. We have previously shown that the matrix metalloproteinase-13 (MMP-13) gene is induced by PTH in osteoblastic cells as a secondary response through the protein kinase A pathway requiring the runt domain and activator protein 1 binding sites of the proximal promoter. Here, we investigated the changes PTH causes in histone acetylation in this region (which contains the only deoxyribonuclease-hypersensitive sites in the promoter) leading to MMP-13 gene activation in these cells. Chromatin immunoprecipitation experiments revealed that PTH rapidly increased histone H4 acetylation followed by histone H3 acetylation associated with the different regions of the MMP-13 proximal promoter. The hormone also stimulated p300 histone acetyl transferase activity and increased p300 bound to the MMP-13 proximal promoter, and this required protein synthesis. Upon PTH treatment, Runx2, already bound to the runt domain site of the MMP-13 promoter, interacted with p300, which then acetylated histones H4 and H3. The knockdown of either Runx2 or p300 by RNA interference reduced PTH-induced acetylation of histones H3 and H4, association of p300 with the MMP-13 promoter, and resultant MMP-13 gene transcription. Overall, our studies suggest that without altering the gross chromatin structure, PTH stimulates acetylation of histones H3 and H4 via recruitment of p300 to Runx2 bound to the MMP-13 promoter, resulting in gene activation. This work establishes the molecular basis of transcriptional regulation in osteoblasts by PTH, a hormone acting through a G-protein coupled receptor.
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