ArticleAmerican journal of physiology. Cell physiology2012
Subcellular relocation of histone deacetylase 4 regulates growth plate chondrocyte differentiation through Ca2+/calmodulin-dependent kinase IV.
Article in American journal of physiology. Cell physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 35 citations in OpenAlex.
- Piezo1-mediated Mechanotransduction in the musculoskeletal system: Signaling networks and therapeutic perspectives.Bone reports · 2026Review
- HDAC4 regulates hASC osteogenesis and bone regeneration by mediating SMAD4 via histone acetylation.Stem cell reports · 2026Article
- Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification.International journal of molecular medicine · 2025Article
- Blocking calcium-MYC regulatory axis inhibits early dedifferentiation of chondrocytes and contributes to cartilage regeneration.Stem cell research & therapy · 2025Article
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Suanzaoren decoction exerts its antidepressant effect via the CaMK signaling pathway.Translational neuroscience · 2024Article
- The Effect of miR-140-5p with HDAC4 towards Growth and Differentiation Signaling of Chondrocytes in Thiram-Induced Tibial Dyschondroplasia.International journal of molecular sciences · 2023Article
- HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis.BMC musculoskeletal disorders · 2022Article
- Histone deacetylase 4 and 5 translocation elicited by microsecond pulsed electric field exposure is mediated by kinase activity.Frontiers in bioengineering and biotechnology · 2022Article
- Senescence marker protein 30 inhibits tumor growth by reducing HDAC4 expression in non-small cell lung cancer.Translational lung cancer research · 2021Article
- The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders.International journal of molecular sciences · 2021Review
- MicroRNA-1 promotes cartilage matrix synthesis and regulates chondrocyte differentiation via post-transcriptional suppression of Ihh expression.Molecular medicine reports · 2020Article
- TET1 Directs Chondrogenic Differentiation by Regulating SOX9 Dependent Activation ofJBMR plus · 2020Article
- Review
- Conditional deletion of HDAC4 from collagen type 2α1-expressing cells increases angiogenesis in vivo.Molecular medicine (Cambridge, Mass.) · 2020Article
- The Role of HDACs and HDACi in Cartilage and Osteoarthritis.Frontiers in cell and developmental biology · 2020Review
- Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development.International journal of molecular sciences · 2019Review
- TMCO1-mediated CaNature communications · 2019Article
- RETRACTED: Compression regulates gene expression of chondrocytes through HDAC4 nuclear relocation via PP2A-dependent HDAC4 dephosphorylation.Biochimica et biophysica acta · 2016Article
- Immediate and long-term transcriptional response of hind muscle tissue to transient variation of incubation temperature in broilers.BMC genomics · 2016Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Regulatory mechanisms of chondrocyte differentiation in the growth plate are incompletely understood. Here, we find that histone deacetylase 4 (HDAC4) is located in the nucleus of chondrocytes in the proliferation zone and relocates to the cytoplasm of chondrocytes in the prehypertrophic zone in vivo. This suggests that the relocation of HDAC4 from the nucleus to the cytoplasm may play a role during chondrocyte differentiation. Expression of active CaMKIV in chondrocytes promotes HDAC4 relocation into cytoplasm in primary chondrocytes. Conversely, HDAC4 relocation is blocked by a Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) inhibitor. This indicates that CaMKIV signaling plays an important role in regulating HDAC4 relocation. In addition, CaMKIV is required for HDAC4 phosphorylation, which is required for HDAC4 association with the cytoplasmic protein 14-3-3. Active CaMKIV also stimulates runt-related transcription factor-2 (RunX2) and type X collagen (Col X) promoter activities and overcomes repression of these promoter activities by HDAC4. Furthermore, CaMKIV increases gene expression of the chondrocyte differentiation markers Ihh and Col X. Our results demonstrate that CaMKIV induces chondrocyte differentiation through regulation of HDAC4 subcellular relocation, from the nucleus to the cytoplasm, which results in increased activity of RunX2 and transition of chondrocytes from the proliferative to the prehypertrophic stage. Thus, CaMKIV plays an important regulatory role during chondrocyte differentiation.
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