ArticleJournal of cellular physiology2017
MAP Kinase-Dependent RUNX2 Phosphorylation Is Necessary for Epigenetic Modification of Chromatin During Osteoblast Differentiation.
Article in Journal of cellular physiology, 2017. 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, 46 citations in OpenAlex.
- RUNX2 enhances vascular remodeling to promote endothelial proliferation in acute liver injury.International journal of biological sciences · 2026Article
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- Parental benzo[a]pyrene exposure impacts histone modifications in osteoblast subpopulations.Environmental epigenetics · 2025Article
- Natural bioactive products in the regulation of bone metabolism and regeneration.Frontiers in pharmacology · 2025Review
- Curculigoside is a Promising Osteoprotective Agent for Osteoporosis: Review.Drug design, development and therapy · 2025Review
- Insight into the role of integrins and integrins-targeting biomaterials in bone regeneration.Connective tissue research · 2024Review
- The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis.International journal of molecular sciences · 2023Review
- MiR-137 promotes TLR4/NF-κB pathway activity through targeting KDM4A, inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis.Journal of orthopaedic surgery and research · 2023Article
- Discoidin domain receptors; an ancient family of collagen receptors has major roles in bone development, regeneration and metabolism.Frontiers in dental medicine · 2023Article
- Antiosteoporosis Effects, Pharmacokinetics, and Drug Delivery Systems of Icaritin: Advances and Prospects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Bu-Gu-Sheng-Sui decoction promotes osteogenesisFrontiers in pharmacology · 2022Article
- Increased osteoclastogenesis contributes to bone loss in the Costello syndromeFrontiers in cell and developmental biology · 2022Article
- Three-dimensional spheroids of dedifferentiated fat cells enhance bone regeneration.Regenerative therapy · 2021Article
- Breast tumor stiffness instructs bone metastasis via maintenance of mechanical conditioning.Cell reports · 2021Article
- Diversity of Vascular Niches in Bones and Joints During Homeostasis, Ageing, and Diseases.Frontiers in immunology · 2021Review
- Curculigoside Ameliorates Bone Loss by Influencing Mesenchymal Stem Cell Fate in Aging Mice.Frontiers in cell and developmental biology · 2021Article
- Runx2 plays a central role in Osteoarthritis development.Journal of orthopaedic translation · 2020Review
- Double-edged effects and mechanisms of ZnRSC advances · 2020Article
- BK ablation attenuates osteoblast bone formation via integrin pathway.Cell death & disease · 2019Article
- Angelica polysaccharide promotes proliferation and osteoblast differentiation of mesenchymal stem cells by regulation of long non-coding RNA H19: An animal study.Bone & joint research · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
RUNX2, an essential transcription factor for osteoblast differentiation and bone formation is activated by ERK/MAP kinase-dependent phosphorylation. However, relationship between these early events and specific epigenetic modifications of chromatin during osteoblast differentiation have not been previously examined. Here, we explore these relationships using chromatin immunoprecipitation (ChIP) to detect chromatin modifications in RUNX2-binding regions of Bglap2 and Ibsp. Growth of MC3T3-E1c4 preosteoblast cells in differentiation conditions rapidly induced Bglap2 and lbsp mRNAs. For both genes, osteogenic stimulation increased chromatin-bound P-ERK, P-RUNX2, p300, and RNA polymerase II as well as histone H3K9 and H4K5 acetylation. The level of H3K4 di-methylation, another gene activation-associated histone mark, also increased. In contrast, levels of the gene repressive marks, H3K9 mono-, di-, and tri-methylation in the same regions were reduced. Inhibition of MAP kinase signaling blocked differentiation-dependent chromatin modifications and Bglap2 and Ibsp expression. To evaluate the role of RUNX2 phosphorylation in these responses, RUNX2-deficient C3H10T1/2 cells were transduced with adenovirus encoding wild type or phosphorylation site mutant RUNX2 (RUNX2 S301A/S319A). Wild type RUNX2, but not the non-phosphorylated mutant, increased H3K9 and H4K5 acetylation as well as chromatin-associated P-ERK, p300, and polymerase II. Thus, RUNX2 phosphorylation is necessary for subsequent epigenetic changes required for osteoblast gene expression. Taken together, this study reveals a molecular mechanism through which osteogenic genes are controlled by a MAPK and P-RUNX2-dependent process involving epigenetic modifications of specific promoter regions. J. Cell. Physiol. 232: 2427-2435, 2017. © 2016 Wiley Periodicals, Inc.
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