ArticleJournal of inflammation research2022
The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.
Article in Journal of inflammation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Bibliometric analysis of research trends and emerging insights of osteoarthritis and chondrocyte hypertrophy.Frontiers in surgery · 2025Pooled it
- Review
- HIF-2α drives osteoarthritis progression via suppression of the HDAC4-ATF4-CHOP signaling axis.PloS one · 2026Article
- Gene Therapy for the Treatment of Osteoarthritis: Advances and Prospective.Current pharmaceutical design · 2026Review
- Article
- HDAC4 regulates apoptosis in Acan-CreFEBS open bio · 2025Article
- Review
- 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
- The N-terminal fragment of histone deacetylase 4 (1-669aa) promotes chondrocyte apoptosis via the p53-dependent endoplasmic reticulum stress pathway.Journal of cellular and molecular medicine · 2024Article
- PP2Ac Regulates Autophagy via Mediating mTORC1 and ULK1 During Osteoclastogenesis in the Subchondral Bone of Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Two Members of Vitamin-K-Dependent Proteins, Gla-Rich Protein (GRP) and Matrix Gla Protein (MGP), as Possible New Players in the Molecular Mechanism of Osteoarthritis.Journal of clinical medicine · 2024Article
- Article
- Inflammatory and Metabolic Signaling Interfaces of the Hypertrophic and Senescent Chondrocyte Phenotypes Associated with Osteoarthritis.International journal of molecular sciences · 2023Review
- The Role of Genetics and Epigenetic Regulation in the Pathogenesis of Osteoarthritis.International journal of molecular sciences · 2023Review
- MicroRNA Signatures in Cartilage Ageing and Osteoarthritis.Biomedicines · 2023Article
- Molecular Mechanisms of Cartilage Repair and Their Possible Clinical Uses: A Review of Recent Developments.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: To determine the role of histone deacetylase 4 (HDAC4)-controlled chondrocyte hypertrophy in the onset and development of age-related osteoarthritis (OA). Methods: Morphological analysis of human knee cartilages was performed to observe structural changes during cartilage degeneration. HDAC4 expression was deleted in adult aggrecan (Acan)-CreERT2; HDAC4fl/fl transgenic mice. The onset and development of age-related OA were investigated in transgenic and control mice using hematoxylin and eosin (H&E) and Safranin O staining. Furthermore, the progression of ACLT-induced OA following adenovirus-mediated HDAC4 overexpression was explored in rats. The expression levels of genes related to hypertrophy, cartilage matrix and its digestion, and chondrocyte proliferation were investigated using qPCR. Immunohistochemistry (IHC) was used to explore the mechanisms underlying HDAC4-controlled age-related changes in OA progression. Results: In human cartilage, we performed morphological analysis and IHC, the results showed that hypertrophy-related structural changes are related to HDAC4 expression. Age-related OA was detected early (OARSI scores 2.7 at 8-month-old) following HDAC4 deletion in 2-month-old mice. Furthermore, qPCR and IHC results showed changes in hypertrophy-related genes Col10a1, Runx2 and Sox9 in chondrocytes, particularly in the expression of Runt-related transcription factor 2 (Runx2, 13.29±0.99 fold). The expression of the main cartilage matrix-related genes Col2a1 and Acan decreased, that of cartilage matrix digestion-related gene MMP-13 increased, while that of chondrocyte proliferation-related genes PTHrP, Ihh and Gli1 changed. In contrast, rat cartilage's qPCR and IHC results showed opposite outcomes after HDAC4 overexpression. Conclusion: Based on the results above, we concluded that HDAC4 expression regulates the onset and development of age-related OA by controlling chondrocyte hypertrophy. These results may help in the development of early diagnosis and treatment of age-related OA.
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Registered trials
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