ArticleInternational journal of biological sciences2013
atf4 promotes β-catenin expression and osteoblastic differentiation of bone marrow mesenchymal stem cells.
Article in International journal of biological sciences, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 75 citations in OpenAlex.
- Bioactive Chitosan Oligosaccharides Derived from Crab Shell Waste Stimulate Osteogenic Differentiation in Pre-Osteoblast Cells.Marine drugs · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- ATF-4 deficiency increases ER stress and induces osteoarthritis formation in mice.Molecular and cellular biochemistry · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- MicroRNA functions in osteogenic differentiation of periodontal ligament stem cells: a scoping review.Frontiers in oral health · 2025Review
- Evaluating the Anti-Osteoporotic Potential of Mediterranean Medicinal Plants: A Review of Current Evidence.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence.International journal of molecular sciences · 2023Review
- The Critical Role of The Piezo1/β-catenin/ATF4 Axis on The Stemness of Gli1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Mechanotransduction Signaling Pathways in the Regulation of Osteogenesis.International journal of molecular sciences · 2023Review
- The role of noncoding RNAs in the osteogenic differentiation of human periodontal ligament-derived cells.Non-coding RNA research · 2023Review
- Osteogenesis of bone marrow mesenchymal stem cell in hyperglycemia.Frontiers in endocrinology · 2023Review
- The Role of Endoplasmic Reticulum Stress in Differentiation of Cells of Mesenchymal Origin.Biochemistry. Biokhimiia · 2022Review
- Magnesium implantation or supplementation ameliorates bone disorder in CFTR-mutant mice through an ATF4-dependent Wnt/β-catenin signaling.Bioactive materials · 2022Article
- Role of histone modification in the occurrence and development of osteoporosis.Frontiers in endocrinology · 2022Review
- A possible connection between reactive oxygen species and the unfolded protein response in lens development: From insight to foresight.Frontiers in cell and developmental biology · 2022Review
- Signaling Pathway and Transcriptional Regulation in Osteoblasts during Bone Healing: Direct Involvement of Hydroxyapatite as a Biomaterial.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Regulation of Osteoblast Differentiation by Cytokine Networks.International journal of molecular sciences · 2021Review
- ATF4 promotes lung cancer cell proliferation and invasion partially through regulating Wnt/β-catenin signaling.International journal of medical sciences · 2021Article
- Accelerated tooth movement in Rsk2-deficient mice with impaired cementum formation.International journal of oral science · 2020Article
- ER stress arm XBP1s plays a pivotal role in proteasome inhibition-induced bone formation.Stem cell research & therapy · 2020Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Bone marrow mesenchymal stem cells (MSCs) can differentiate into multiple cell types including osteoblasts. How this differentiation process is controlled, however, is not completely understood. Here we show that activating transcription factor 4 (ATF4) plays a critical role in promoting bone marrow MSC differentiation towards the osteoblast lineage. Ablation of the Atf4 gene blocked the formation of osteoprogenitors and inhibited osteoblast differentiation without affecting the expansion and formation of MSCs in bone marrow cultures. Loss of ATF4 dramatically reduced the level of β-catenin protein in MSCs in vitro and in osteoblasts/osteoprogenitors located on trabecular and calvarial surfaces. Loss of ATF4 did not decrease the expression of major canonical Wnt/β-catenin signaling components such as Wnt3a, Wnt7b, Wnt10b, Lrp5, and Lrp6 in MSCs. Furthermore, shRNA knockdown of ATF4 expression decreased the level of β-catenin protein in MC-4 preosteoblasts. In contrast, overexpression of ATF4 increased β-catenin protein levels in MC-4 cells. Finally, ATF4 and β-catenin formed a protein-protein complex in COS-7 cells coexpressing both factors or in MC-4 preosteoblastic cells. This study establishes a new role of ATF4 in controlling the β-catenin protein levels and MSC differentiation towards the osteoblast lineage.
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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.