ArticleDevelopment (Cambridge, England)2009
Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription.
Article in Development (Cambridge, England), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 117 citations in OpenAlex.
- Spatiotemporal Regulation and Lineage Specification in Embryonic Endochondral Ossification.International journal of molecular sciences · 2026Review
- Differential regulation of coronal and lambdoid suture patency by PTHLH and HHIP activity in mice.Development (Cambridge, England) · 2025Article
- Ribosomal protein deficiencies linked to Diamond-Blackfan anemia induce distinctive alterations of ATF4 expression.iScience · 2025Article
- The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes.Nature metabolism · 2025Article
- Zfp260 choreographs the early stage osteo-lineage commitment of skeletal stem cells.Nature communications · 2024Article
- ER procollagen storage defect without coupled unfolded protein response drives precocious arthritis.Life science alliance · 2024Article
- Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence.International journal of molecular sciences · 2023Review
- Runt-related Transcription Factors and Gene Regulatory Mechanisms in Skeletal Development and Diseases.Current osteoporosis reports · 2023Review
- Comparative transcriptome analysis provides insight into the molecular targets and signaling pathways of deer TGF-1 regulating chondrocytes proliferation and differentiation.Molecular biology reports · 2023Article
- Emerging RUNX2-Mediated Gene Regulatory Mechanisms Consisting of Multi-Layered Regulatory Networks in Skeletal Development.International journal of molecular sciences · 2023Review
- MicroRNAs-mediated regulation pathways in rheumatic diseases.Inflammopharmacology · 2023Review
- Amino acid metabolism in skeletal cells.Bone reports · 2022Article
- Runx2 regulates chromatin accessibility to direct the osteoblast program at neonatal stages.Cell reports · 2022Article
- Comparison of Gene Expression Patterns in Articular Cartilage and Xiphoid Cartilage.Biochemical genetics · 2022Article
- De novo serine synthesis regulates chondrocyte proliferation during bone development and repair.Bone research · 2022Article
- Limb Mesoderm and Head Ectomesenchyme Both Express a Core Transcriptional Program During Chondrocyte Differentiation.Frontiers in cell and developmental biology · 2022Article
- Gibberellic Acid Initiates ER Stress and Activation of Differentiation in Cultured Human Immortalized Keratinocytes HaCaT and Epidermoid Carcinoma Cells A431.Pharmaceutics · 2021Article
- Targeting the integrated stress response in ophthalmology.Current eye research · 2021Review
- The Role of BMP Signaling in Osteoclast Regulation.Journal of developmental biology · 2021Review
- Regulation and Role of Transcription Factors in Osteogenesis.International journal of molecular sciences · 2021Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Activating transcription factor 4 (Atf4) is a leucine-zipper-containing protein of the cAMP response element-binding protein (CREB) family. Ablation of Atf4 (Atf4(-/-)) in mice leads to severe skeletal defects, including delayed ossification and low bone mass, short stature and short limbs. Atf4 is expressed in proliferative and prehypertrophic growth plate chondrocytes, suggesting an autonomous function of Atf4 in chondrocytes during endochondral ossification. In Atf4(-/-) growth plate, the typical columnar structure of proliferative chondrocytes is disturbed. The proliferative zone is shortened, whereas the hypertrophic zone is transiently expanded. The expression of Indian hedgehog (Ihh) is markedly decreased, whereas the expression of other chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal. Furthermore, forced expression of Atf4 in chondrocytes induces endogenous Ihh mRNA, and Atf4 directly binds to the Ihh promoter and activates its transcription. Supporting these findings, reactivation of Hh signaling pharmacologically in mouse limb explants corrects the Atf4(-/-) chondrocyte proliferation and short limb phenotypes. This study thus identifies Atf4 as a novel transcriptional activator of Ihh in chondrocytes that paces longitudinal bone growth by controlling growth plate chondrocyte proliferation and differentiation.
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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.