ArticleBone2021
PTHrP targets salt-inducible kinases, HDAC4 and HDAC5, to repress chondrocyte hypertrophy in the growth plate.
Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 18 citations in OpenAlex.
- Spatial control of parathyroid hormone receptor-1 signaling dictates ligand-specific biological outcomes.Signal transduction and targeted therapy · 2026Article
- Skeletal dysplasias of the parathyroid hormone signaling cascade: radiological manifestations and molecular mechanisms.Pediatric radiology · 2026Review
- Humanized mice to model rare human diseases.Proceedings of the National Academy of Sciences of the United States of America · 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
- Versatility of 14-3-3 proteins and their roles in bone and joint-related diseases.Bone research · 2024Review
- Targeting SIK3 to modulate hippocampal synaptic plasticity and cognitive function by regulating the transcription of HDAC4 in a mouse model of Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Growth disorders caused by variants in epigenetic regulators: progress and prospects.Frontiers in endocrinology · 2024Review
- Unveiling the Role of Sik1 in Osteoblast Differentiation: Implications for Osteoarthritis.Molecular and cellular biology · 2024Article
- The multiple roles of salt-inducible kinases in regulating physiology.Physiological reviews · 2023Review
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- PTH, FGF-23, Klotho and Vitamin D as regulators of calcium and phosphorus: Genetics, epigenetics and beyond.Frontiers in endocrinology · 2022Review
- Factors affecting prepubertal and pubertal bone age progression.Frontiers in endocrinology · 2022Review
- The Level of Histone Deacetylase 4 is Associated with Aging Cartilage Degeneration and Chondrocyte Hypertrophy.Journal of inflammation research · 2022Article
- Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypertrophy of chondrocytes is a crucial step in the endochondral bone formation process that drives bone lengthening and the transition to endochondral bone formation. Both Parathyroid hormone-related protein (PTHrP) and Histone deacetylase 4 (HDAC4) inhibit chondrocyte hypertrophy. Use of multiple mouse genetics models reveals how PTHrP and HDAC4 participate in a pathway that regulates chondrocyte hypertrophy. PTHrP/cAMP/protein kinase A (PKA) signaling pathway phosphorylates the PKA-target sites on salt-inducible kinase 3 (Sik3), which leads to inhibition of Sik3 kinase activity. Inhibition of Sik3 kinase activity decreases phosphorylation of HDAC4 by Sik3 at binding sites for 14-3-3; lower levels of HDAC4 phosphorylation then allow HDAC4 nuclear translocation. In the nucleus, the transcription factor, Myocyte Enhancer Factor 2 (Mef2), activates Runt-related transcription factor 2 (Runx2), and together these two transcription factors drive the hypertrophic process. HDAC4 binds both Mef2 and Runx2 and blocks their activities. There are genetic redundancies in this pathway. Sik1 and Sik2 also mediate PTHrP/cAMP/PKA signaling when Sik3 activity is low. HDAC5 also mediates PTHrP signaling when HDAC4 expression is low. Thus, PTHrP triggers a kinase cascade that leads to inhibition of the key transcription factors (Mef2 and Runx2) that promote chondrocyte hypertrophy.
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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.