ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2009
Dose-dependent effects of Runx2 on bone development.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
- Toward improved phosphorus efficiency in monogastrics-interplay of serum, minerals, bone, and immune system after divergent dietary phosphorus supply in swine.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Trial
- Neddylation of NFATc1 and Runx2 regulates osteoclast-osteoblast balance and represents a dual-action therapeutic target for postmenopausal osteoporosis.Experimental & molecular medicine · 2026Article
- Branch site mutated mice revealed distinct roles of two Runx2 isoforms in bone development.Frontiers in cell and developmental biology · 2026Article
- Non-Canonical TERT Activity Initiates Osteogenesis in Calcific Aortic Valve Disease.Circulation research · 2025Article
- Progress on the mechanism of Polycystin-1 in bone remodeling.Frontiers in cell and developmental biology · 2025Review
- CCAAT/Enhancer-Binding Protein β (C/EBPβ) Regulates Calcium Deposition in Smooth Muscle Cells.International journal of molecular sciences · 2024Article
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- Evolutionary mechanisms modulating the mammalian skull development.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- METTL5 regulates cranial suture fusion via Wnt signaling.Fundamental research · 2023Article
- The Role of the Piezo1 Mechanosensitive Channel in the Musculoskeletal System.International journal of molecular sciences · 2023Review
- Review
- Article
- Mouse embryo phenotyping using X-ray microCT.Frontiers in cell and developmental biology · 2022Review
- Shaping modern human skull through epigenetic, transcriptional and post-transcriptional regulation of the RUNX2 master bone gene.Scientific reports · 2021Article
- Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues.Bone research · 2021Review
- Evolution and expansion of the RUNX2 QA repeat corresponds with the emergence of vertebrate complexity.Communications biology · 2020Review
- Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.International journal of molecular sciences · 2020Review
- Review
- Influence of Maitake (BioMed research international · 2020Article
- Prickle1 regulates differentiation of frontal bone osteoblasts.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Runx2 controls the commitment of mesenchymal cells to the osteoblastic lineage. Distinct promoters, designated P1 and P2, give rise to functionally similar Runx2-II and Runx2-I isoforms. We postulate that this dual promoter gene structure permits temporal and spatial adjustments in the amount of Runx2 isoforms necessary for optimal bone development. To evaluate the gene dose-dependent effect of Runx2 isoforms on bone development, we intercrossed selective Runx2-II(+/-) with nonselective Runx2-II(+/-)/Runx2-I(+/-) mice to create compound mutant mice: Runx2-II(+/-), Runx2-II(+/-)/Runx2-I(+/-), Runx2-II(-/-), Runx2-II(-/-)/Runx2-I(+/-), Runx2-II(-/-)/Runx2-I(-/-). Analysis of the different Runx2-deficient genotypes showed gene dose-dependent differences in the level of expression of the Runx2 isoforms. In addition, we found that Runx2-I is predominately expressed in the perichondrium and proliferating chondrocytes, whereas Runx2-II is expressed in hypertrophic chondrocytes and metaphyseal osteoblasts. Newborn mice showed impaired development of a mineralized skeleton, bone length, and widening of the hypertrophic zone that were proportionate to the reduction in total Runx2 protein expression. Osteoblast differentiation ex vivo was also proportionate to total amount of Runx2 expression that correlated with reduced Runx2 binding to the osteocalcin promoter by quantitative chromatin immunoprecipitation analysis. Functional analysis of P1 and P2 promoters showed differential regulation of the two promoters in osteoblastic cell lines. These findings support the possibility that the total amount of Runx2 derived from two isoforms and the P1 and P2 promoters, by regulating the time, place, and amount of Runx2 in response to changing environmental cues, impacts on bone development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.