ArticleJCI insight2019
PTHrP targets HDAC4 and HDAC5 to repress chondrocyte hypertrophy.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Immunity-and-matrix-regulatory cells promote hyaline-like cartilage repair in osteoarthritis.Bioactive materials · 2026Article
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Comprehensive mass spectrometry screening-derived atlas of HDAC inhibitors reveals histone-specific acetylation changes.Cell reports · 2026Article
- Stage-Specific Expression of Histone Deacetylases in the Mouse Mandibular Condylar Cartilage.Cartilage · 2025Article
- A mouse model of Jansen's metaphyseal chondrodysplasia for investigating disease mechanisms and candidate therapeutics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Revolutionizing the treatment of intervertebral disc degeneration: an approach based on molecular typing.Journal of translational medicine · 2025Article
- The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024Article
- PTHrP participates in the bone destruction of middle ear cholesteatoma via promoting macrophage differentiation into osteoclasts induced by RANKL.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Enhanced articular cartilage regeneration using costal chondrocyte-derived scaffold-free tissue engineered constructs with ascorbic acid treatment.Journal of orthopaedic translation · 2024Article
- Scoping Pleiotropy of CK2 in Musculoskeletal Disorders for a Novel Targeting Approach.Kinases and phosphatases · 2024Article
- Growth disorders caused by variants in epigenetic regulators: progress and prospects.Frontiers in endocrinology · 2024Review
- The nuclear localization sequence and C-terminus of parathyroid hormone-related protein regulate normal pancreatic islet development and function.General and comparative endocrinology · 2023Article
- Review
- Article
- Epigenetic therapy targeting bone marrow mesenchymal stem cells for age-related bone diseases.Stem cell research & therapy · 2022Review
- HDAC4 mutant represses chondrocyte hypertrophy by locating in the nucleus and attenuates disease progression of posttraumatic osteoarthritis.BMC musculoskeletal disorders · 2022Article
- The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.Journal of inflammation research · 2022Article
- PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.Frontiers in endocrinology · 2022Review
- In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Genes with specificity for expression in the round cell layer of the growth plate are enriched in genomewide association study (GWAS) of human height.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
During endochondral bone formation, chondrocyte hypertrophy represents a crucial turning point from chondrocyte differentiation to bone formation. Both parathyroid hormone-related protein (PTHrP) and histone deacetylase 4 (HDAC4) inhibit chondrocyte hypertrophy. Using multiple mouse genetics models, we demonstrate in vivo that HDAC4 is required for the effects of PTHrP on chondrocyte differentiation. We further show in vivo that PTHrP leads to reduced HDAC4 phosphorylation at the 14-3-3-binding sites and subsequent HDAC4 nuclear translocation. The Hdac4-KO mouse shares a similar but milder phenotype with the Pthrp-KO mouse, indicating the possible existence of other mediators of PTHrP action. We identify HDAC5 as an additional mediator of PTHrP signaling. While the Hdac5-KO mouse has no growth plate phenotype at birth, the KO of Hdac5 in addition to the KO of Hdac4 is required to block fully PTHrP action on chondrocyte differentiation at birth in vivo. Finally, we show that PTHrP suppresses myocyte enhancer factor 2 (Mef2) action that allows runt-related transcription factor 2 (Runx2) mRNA expression needed for chondrocyte hypertrophy. Our results demonstrate that PTHrP inhibits chondrocyte hypertrophy and subsequent bone formation in vivo by allowing HDAC4 and HDAC5 to block the Mef2/Runx2 signaling cascade. These results explain the phenotypes of several genetic abnormalities in humans.
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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.