ArticleBone2014
The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.
Article in Bone, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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
26 citing papers in PubMed, 55 citations in OpenAlex.
- Article
- Effect of Canagliflozin Pretreatment on the Efficacy of Insulin Therapy to Rescue Type 1 Diabetes-Related Bone Fragility in Male Mice.Calcified tissue international · 2026Article
- Data-driven inference of Boolean networks from transcriptomes to predict cellular differentiation and reprogramming.NPJ systems biology and applications · 2025Article
- Review
- Obese-diabetic femaleJBMR plus · 2025Article
- The Critical Role of The Piezo1/β-catenin/ATF4 Axis on The Stemness of Gli1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Tanshinone IIA attenuates valvular interstitial cells' calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress.Open medicine (Warsaw, Poland) · 2023Article
- Poor bone matrix quality: What can be done about it?Current osteoporosis reports · 2021Review
- Regulation and Role of Transcription Factors in Osteogenesis.International journal of molecular sciences · 2021Review
- Spatial-Temporal Patterns and Inflammatory Factors of Bone Matrix Remodeling.Stem cells international · 2021Review
- ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation.Stem cell research & therapy · 2020Article
- Validation of reference genes for expression analysis in a murine trauma model combining traumatic brain injury and femoral fracture.Scientific reports · 2020Article
- Article
- Inhibition of vascular endothelial growth factor in young adult mice causes low bone blood flow and bone strength with no effect on bone mass in trabecular regions.Bone reports · 2019Article
- Reactivation of a developmentaleLife · 2019Article
- The Role of Matrix Composition in the Mechanical Behavior of Bone.Current osteoporosis reports · 2018Review
- Low bone toughness in the TallyHO model of juvenile type 2 diabetes does not worsen with age.Bone · 2018Article
- Vibrational spectroscopic techniques to assess bone quality.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2017Review
- Changes in the Fracture Resistance of Bone with the Progression of Type 2 Diabetes in the ZDSD Rat.Calcified tissue international · 2016Article
- Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness.
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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.