ArticleCell death & disease2013
Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- Engineering 3D-BMSC exosome-based hydrogels that collaboratively regulate bone microenvironment and promote osteogenesis for enhanced cell-free bone regeneration.Materials today. Bio · 2025Article
- Exercise mediates myocardial infarction via non-coding RNAs.Frontiers in cardiovascular medicine · 2024Review
- Epidermal growth factor signalling pathway in endochondral ossification: an evidence-based narrative review.Annals of medicine · 2022Review
- The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials.Frontiers in bioengineering and biotechnology · 2022Review
- MicroRNA-218 competes with differentiation media in the induction of osteogenic differentiation of mesenchymal stem cell by regulating β-catenin inhibitors.Molecular biology reports · 2020Article
- Functions of Circular RNAs in Regulating Adipogenesis of Mesenchymal Stem Cells.Stem cells international · 2020Review
- Article
- miR‑488 negatively regulates osteogenic differentiation of bone marrow mesenchymal stem cells induced by psoralen by targeting Runx2.Molecular medicine reports · 2019Article
- FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition.Nucleic acids research · 2019Article
- Roles for HB-EGF in Mesenchymal Stromal Cell Proliferation and Differentiation During Skeletal Growth.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Epidermal growth factor can signal via β-catenin to control proliferation of mesenchymal stem cells independently of canonical Wnt signalling.Cellular signalling · 2019Article
- Investigating the Osteoinductive Potential of a Decellularized Xenograft Bone Substitute.Cells, tissues, organs · 2019Article
- Knockdown of FOXA2 enhances the osteogenic differentiation of bone marrow-derived mesenchymal stem cells partly via activation of the ERK signalling pathway.Cell death & disease · 2018Article
- Article
- microRNA Regulation of Skeletal Development.Current osteoporosis reports · 2017Review
- MicroRNAs in bone diseases.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Review
- EGF receptor ligands: recent advances.F1000Research · 2016Review
- miR-216a rescues dexamethasone suppression of osteogenesis, promotes osteoblast differentiation and enhances bone formation, by regulating c-Cbl-mediated PI3K/AKT pathway.Cell death and differentiation · 2015Article
- CREB1-driven expression of miR-320a promotes mitophagy by down-regulating VDAC1 expression during serum starvation in cervical cancer cells.Oncotarget · 2015Article
- The role of microRNAs in bone remodeling.International journal of oral science · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoblast differentiation is a pivotal event in bone formation. Runt-related transcription factor-2 (Runx2) is an essential factor required for osteoblast differentiation and bone formation. However, the underlying mechanism of Runx2-regulated osteogenic differentiation is still unclear. Here, we explored the corresponding mechanism using the C2C12/Runx2(Dox) subline, which expresses Runx2 in response to doxycycline (Dox). We found that Runx2-induced osteogenic differentiation of C2C12 cells results in a sustained decrease in the expression of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family. Forced expression of HB-EGF or treatment with HB-EGF is capable of reducing the expression of alkaline phosphatase (ALP), a defined marker of early osteoblast differentiation. HB-EGF-mediated inhibition of ALP depends upon activation of the EGFR and the downstream extracellular signal-regulated kinase, c-Jun N-terminal kinase mitogen-activated protein kinase pathways as well as phosphatidylinositol 3-kinase/Akt pathway. Runx2 specifically binds to the Hbegf promoter, suggesting that Hbegf transcription is directly inhibited by Runx2. Runx2 can upregulate miR-1192, which enhances Runx2-induced osteogenic differentiation. Moreover, miR-1192 directly targets Hbegf through translational inhibition, suggesting enhancement of Runx2-induced osteogenic differentiation by miR-1192 through the downregulation of HB-EGF. Taken together, our results suggest that Runx2 induces osteogenic differentiation of C2C12 cells by inactivating HB-EGF-EGFR signaling through the downregulation of HB-EGF via both transcriptional and post-transcriptional mechanisms.
Indexed as
Identifiers
What OpenQuestion holds
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.