ArticleThe Journal of biological chemistry2005
A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation.
Article in The Journal of biological chemistry, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- JUNB and JUND in Urological Cancers: A Literature Review.Current issues in molecular biology · 2025Review
- Targeting Chondrocyte Hypertrophy as Strategies for the Treatment of Osteoarthritis.Bioengineering (Basel, Switzerland) · 2025Review
- A High-Fat Diet Induces Epigenetic 1-Carbon Metabolism, Homocystinuria, and Renal-Dependent HFpEF.Nutrients · 2025Article
- Epigenetics of Homocystinuria, Hydrogen Sulfide, and Circadian Clock Ablation in Cardiovascular-Renal Disease.Current issues in molecular biology · 2024Review
- Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2024Article
- Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells.Cell communication and signaling : CCS · 2024Article
- Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis.International journal of molecular sciences · 2023Review
- Novel mechanism of the COVID-19 associated coagulopathy (CAC) and vascular thromboembolism.Npj viruses · 2023Article
- Hydrogen sulfide mitigates skeletal muscle mitophagy-led tissue remodeling via epigenetic regulation of the gene writer and eraser function.Physiological reports · 2022Article
- Two Modulators of Skeletal Development: BMPs and Proteoglycans.Journal of developmental biology · 2022Review
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Gadd45 in Normal Hematopoiesis and Leukemia.Advances in experimental medicine and biology · 2022Article
- Roles for GADD45 in Development and Cancer.Advances in experimental medicine and biology · 2022Review
- GADD45 in Stress Signaling, Cell Cycle Control, and Apoptosis.Advances in experimental medicine and biology · 2022Article
- Expression Profiling and Functional Analysis of CandidateFrontiers in genetics · 2021Article
- Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways.Journal of natural medicines · 2019Article
- Systems biology reveals how altered TGFβ signalling with age reduces protection against pro-inflammatory stimuli.PLoS computational biology · 2019Article
- Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair.Cellular and molecular life sciences : CMLS · 2017Review
- Gene Expression Analysis Reveals the Concurrent Activation of Proapoptotic and Antioxidant-Defensive Mechanisms in Flavokawain B-Treated Cervical Cancer HeLa Cells.Integrative cancer therapies · 2017Article
- XBP1-Independent UPR Pathways Suppress C/EBP-β Mediated Chondrocyte Differentiation in ER-Stress Related Skeletal Disease.PLoS genetics · 2015Article
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
The growth arrest and DNA damage-inducible 45beta (GADD45beta) gene product has been implicated in the stress response, cell cycle arrest, and apoptosis. Here we demonstrated the unexpected expression of GADD45beta in the embryonic growth plate and uncovered its novel role as an essential mediator of matrix metalloproteinase-13 (MMP-13) expression during terminal chondrocyte differentiation. We identified GADD45beta as a prominent early response gene induced by bone morphogenetic protein-2 (BMP-2) through a Smad1/Runx2-dependent pathway. Because this pathway is involved in skeletal development, we examined mouse embryonic growth plates, and we observed expression of Gadd45beta mRNA coincident with Runx2 protein in pre-hypertrophic chondrocytes, whereas GADD45beta protein was localized prominently in the nucleus in late stage hypertrophic chondrocytes where Mmp-13 mRNA was expressed. In Gadd45beta(-/-) mouse embryos, defective mineralization and decreased bone growth accompanied deficient Mmp-13 and Col10a1 gene expression in the hypertrophic zone. Transduction of small interfering RNA-GADD45beta in epiphyseal chondrocytes in vitro blocked terminal differentiation and the associated expression of Mmp-13 and Col10a1 mRNA in vitro. Finally, GADD45beta stimulated MMP-13 promoter activity in chondrocytes through the JNK-mediated phosphorylation of JunD, partnered with Fra2, in synergy with Runx2. These observations indicated that GADD45beta plays an essential role during chondrocyte terminal differentiation.
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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.