ArticleCell death & disease2018
CCN3 and DLL1 co-regulate osteogenic differentiation of mouse embryonic fibroblasts in a Hey1-dependent manner.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- EZH2 directs HER2+ breast cancer progression through the modulation of epithelial plasticity.EMBO reports · 2026Article
- The Relationship Between CCN3 and Rheumatoid Arthritis and Its Potential Therapeutic Value.Journal of immunology research · 2026Review
- IRX3 controls a SUMOylation-dependent differentiation switch in adipocyte precursor cells.Nature communications · 2025Article
- CCN Proteins as Matricellular Regulators of Bone in Aging and Disease.Current osteoporosis reports · 2025Review
- Exploring the Role of Ccn3 in Type III Cell of Mice Taste Buds.Journal of neurochemistry · 2025Article
- OGT mediated HDAC5 O-GlcNAcylation promotes osteogenesis by regulating the homeostasis of epigenetic modifications and proteolysis.Journal of orthopaedic translation · 2025Article
- Integrin αVβ3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Simulation and Computational Study of RING Domain Mutants of BRCA1 and Ube2k in AD/PD Pathophysiology.Molecular biotechnology · 2024Article
- Article
- Danlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction.Frontiers in pharmacology · 2024Article
- CCN3/NOV Regulates Proliferation and Neuronal Differentiation in Mouse Hippocampal Neural Stem Cells via the Activation of the Notch/PTEN/AKT Pathway.International journal of molecular sciences · 2023Article
- Myeloid CCN3 protects against aortic valve calcification.Cell communication and signaling : CCS · 2023Article
- TAZ promotes osteogenic differentiation of mesenchymal stem cells line C3H10T1/2, murine multi-lineage cells lines C2C12, and MEFs induced by BMP9.Cell death discovery · 2022Article
- Molecular and Genetic Interactions between CCN2 and CCN3 behind Their Yin-Yang Collaboration.International journal of molecular sciences · 2022Review
- Cellular communication network factor 3 in cartilage development and maintenance.Journal of cell communication and signaling · 2021Review
- Article
- [Regulatory effect of CCN3 on proliferation of mouse embryonic fibroblasts and its mechanism].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021Article
- Schnurri-3 regulates BMP9-induced osteogenic differentiation and angiogenesis of human amniotic mesenchymal stem cells through Runx2 and VEGF.Cell death & disease · 2020Article
- Delta Like-1 Gene Mutation: A Novel Cause of Congenital Vertebral Malformation.Frontiers in genetics · 2019Article
- Differential expression of Notch related genes in dental pulp stem cells and stem cells isolated from apical papilla.Journal of oral biology and craniofacial researchArticle
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Notch signaling pathway is one of the most important pathways to regulate intercellular signal transduction and is crucial in the regulation of bone regeneration. Nephroblastoma overexpressed (NOV or CCN3) serves as a non-canonical secreted ligand of Notch signaling pathway and its role in the process of osteogenic differentiation of mesenchymal stem cells (MSCs) was undefined. Here we conducted a comprehensive study on this issue. In vivo and in vitro studies have shown that CCN3 significantly inhibited the early and late osteogenic differentiation of mouse embryonic fibroblasts (MEFs), the expression of osteogenesis-related factors, and the subcutaneous ectopic osteogenesis of MEFs in nude mice. In mechanism studies, we found that CCN3 significantly inhibited the expression of BMP9 and the activation of BMP/Smad and BMP/MAPK signaling pathways. There was also a mutual inhibition between CCN3 and DLL1, one of the classic membrane protein ligands of Notch signaling pathway. Additionally, we further found that Hey1, the target gene shared by BMP and Notch signaling pathways, partially reversed the inhibitory effect of CCN3 on osteoblastic differentiation of MEFs. In summary, our findings suggested that CCN3 significantly inhibited the osteogenic differentiation of MEFs. The inhibitory effect of CCN3 was mainly through the inhibition of BMP signaling and the mutual inhibition with DLL1, so as to inhibit the expression of Hey1, the target gene shared by BMP and Notch signaling pathways.
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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 Socratic graph.