ArticleBiochimica et biophysica acta2015
Mitogen-activated protein kinase p38 induces HDAC4 degradation in hypertrophic chondrocytes.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- HBP-A Attenuates Knee Osteoarthritis Progression via MLK3/P38/HDAC4 Axis-Mediated Dual Protection of Articular Cartilage and Quadriceps.Journal of cellular and molecular medicine · 2025Article
- The Molecular Mechanism Investigation of HBP-A Slows Down Meniscus Hypertrophy and Mineralisation by the Damage Mechanical Model.Journal of cellular and molecular medicine · 2024Article
- Mechanism and application of feedback loops formed by mechanotransduction and histone modifications.Genes & diseases · 2024Review
- HDAC4 in cancer: A multitasking platform to drive not only epigenetic modifications.Frontiers in molecular biosciences · 2023Review
- Histone deacetylase 4 deletion results in abnormal chondrocyte hypertrophy and premature ossification from collagen type 2α1‑expressing cells.Molecular medicine reports · 2020Article
- Review
- Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo.Molecular medicine (Cambridge, Mass.) · 2020Article
- Expression and Role of IL-1β Signaling in Chondrocytes Associated with Retinoid Signaling during Fracture Healing.International journal of molecular sciences · 2020Article
- The role of histone deacetylase 4 during chondrocyte hypertrophy and endochondral bone development.Bone & joint research · 2020Review
- Hypertrophic differentiation of mesenchymal stem cells is suppressed by xanthotoxin via the p38‑MAPK/HDAC4 pathway.Molecular medicine reports · 2017Article
- RETRACTED: Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation.Biochimica et biophysica acta · 2016Article
- Cyclic Equibiaxial Tensile Strain Alters Gene Expression of Chondrocytes via Histone Deacetylase 4 Shuttling.PloS one · 2016Article
- Tissue-specific up-regulation of arginase I and II induced by p38 MAPK mediates endothelial dysfunction in type 1 diabetes mellitus.British journal of pharmacology · 2015Article
- Focus on the p38 MAPK signaling pathway in bone development and maintenance.BoneKEy reports · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Histone deacetylase 4 (HDAC4) is a critical negative regulator for chondrocyte hypertrophy by binding to and inhibiting Runx2, a critical transcription factor for chondrocyte hypertrophy. It is unclear how HDAC4 expression and stability are regulated during growth plate development. We report here that inhibition of mitogen-activated protein kinase (MAPK) p38 by dominant negative p38 or p38 inhibitor prevents HDAC4 degradation. Mutation of a potential caspase-2 and 3 cleavage site Asp289 stabilizes HDAC4 in chondrocytes. In contrast, constitutively active MAPK kinase 6 (constitutive activator of p38) transgenic mice exhibit decreased HDAC4 content in vivo. We also observed that p38 stimulates caspase-3 activity in chondrocytes. Inhibition of p38 or caspases reduced HDAC4 degradation. HDAC4 inhibited Runx2 promoter activity in a dose-dependent manner and caspase inhibitors further enhanced this inhibition by preventing HDAC4 degradation. Overall, these results demonstrate that p38 promotes HDAC4 degradation by increasing caspase-mediated cleavage, which releases Runx2 from a repressive influence of HDAC4 and promotes the chondrocyte hypertrophy and bone formation.
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Registered trials
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