ArticlePloS one2009
Critical role of activating transcription factor 4 in the anabolic actions of parathyroid hormone in bone.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 73 citations in OpenAlex.
- Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.The Journal of biological chemistry · 2013Trial
- Role of ATF7-TAF12 interactions in the vitamin D response hypersensitivity of osteoclast precursors in Paget's disease.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Trial
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Bone repair and key signalling pathways for cell-based bone regenerative therapy: A review.Journal of Taibah University Medical Sciences · 2023Review
- Assembling the Puzzle Pieces. Insights for in Vitro Bone Remodeling.Stem cell reviews and reports · 2023Review
- The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.Biochemistry. Biokhimiia · 2022Review
- Fluid Shear Stress Promotes Osteoblast Proliferation and Suppresses Mitochondrial-Mediated Osteoblast Apoptosis Through the miR-214-3p-ATF4 Signaling Axis.Physiological research · 2022Article
- Systemic Administration of Recombinant Irisin Accelerates Fracture Healing in Mice.International journal of molecular sciences · 2021Article
- Anabolic actions of PTH in murine models: two decades of insights.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- Paracrine Kynurenic Pathway Activation in the Bone of Young Uremic Rats Can Antagonize Anabolic Effects of PTH on Bone Turnover and Strength through the Disruption of PTH-Dependent Molecular Signaling.International journal of molecular sciences · 2021Article
- Regulation and Role of Transcription Factors in Osteogenesis.International journal of molecular sciences · 2021Review
- Molecular mechanisms of intermuscular bone development in fish: a review.Zoological research · 2021Review
- Exogenous PTH 1-34 Attenuates Impaired Fracture Healing in Endogenous PTH Deficiency Mice via Activating Indian Hedgehog Signaling Pathway and Accelerating Endochondral Ossification.Frontiers in cell and developmental biology · 2021Article
- CircMAP3K11 Contributes to Proliferation, Apoptosis and Migration of Human Periodontal Ligament Stem Cells in Inflammatory Microenvironment by Regulating TLR4 via miR-511 Sponging.Frontiers in pharmacology · 2021Article
- Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice.Signal transduction and targeted therapy · 2020Article
- Accelerated tooth movement in Rsk2-deficient mice with impaired cementum formation.International journal of oral science · 2020Article
- Prospect of Stem Cell Therapy and Regenerative Medicine in Osteoporosis.Frontiers in endocrinology · 2020Review
- Evidences for a New Role of miR-214 in Chondrogenesis.Scientific reports · 2018Article
- Intermittent Administration of Parathyroid Hormone 1-34 Enhances Osteogenesis of Human Mesenchymal Stem Cells by Regulating Protein Kinase Cδ.International journal of molecular sciences · 2017Article
- MicroRNA-214 Suppresses Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Targeting ATF4.Stem cells international · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4). Our study demonstrates that ATF4 deficiency suppresses PTH-stimulated osteoblast proliferation and survival and abolishes PTH-induced osteoblast differentiation, which, together, compromise the anabolic response. We further demonstrate that the PTH-dependent increase in osteoblast differentiation is correlated with ATF4-dependent up-regulation of Osterix. This regulation involves interactions of ATF4 with a specific enhancer sequence in the Osterix promoter. Furthermore, actions of PTH on Osterix require this same element and are associated with increased binding of ATF4 to chromatin. Taken together these experiments establish a fundamental role for ATF4 in the anabolic actions of PTH on the skeleton.
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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.