ArticleThe Journal of clinical investigation2010
Activating transcription factor 4 regulates osteoclast differentiation in mice.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 95 citations in OpenAlex.
- Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.The Journal of biological chemistry · 2013Trial
- Trial
- Lapatinib Induces Ferroptosis in Cardiomyocytes by Regulating ATF4/GPX4.Cardiovascular toxicology · 2026Article
- Targeting the Ip6k2-Runx2 axis disrupts osteoblast-osteoclast coupling to treat osteoporosis.Nature communications · 2026Article
- Sialin-STAT3 axis regulates bone homeostasis in mice.Bone research · 2026Article
- Enhancing Bone Healing Using Carvacrol on Calcium Phosphate Substrates.ACS applied materials & interfaces · 2026Article
- ATF-4 deficiency increases ER stress and induces osteoarthritis formation in mice.Molecular and cellular biochemistry · 2025Article
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- The p53-miR17 family-Rankl axis bridges liver-bone communication.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints.Nature communications · 2024Article
- Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints.bioRxiv : the preprint server for biology · 2023Article
- [Oridonin suppresses the effect of thioacetamide for promoting osteoclast differentiation of RAW264.7 cells and inhibiting osteoblast differentiation of bone mesenchymal stem cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2023Article
- Targeting Kindlin-2 in adipocytes increases bone mass through inhibiting FAS/PPARActa pharmaceutica Sinica. B · 2023Article
- Osteoclast microRNA Profiling in Rheumatoid Arthritis to Capture the Erosive Factor.JBMR plus · 2023Article
- Article
- Bone and the Unfolded Protein Response: In Sickness and in Health.Calcified tissue international · 2023Review
- Oridonin Attenuates Thioacetamide-Induced Osteoclastogenesis Through MAPK/NF-κB Pathway and Thioacetamide-Inhibited Osteoblastogenesis Through BMP-2/RUNX2 Pathway.Calcified tissue international · 2023Article
- FTY720 Attenuates LPS-Induced Inflammatory Bone Loss by Inhibiting Osteoclastogenesis via the NF-Journal of immunology research · 2023Article
6 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
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Activating transcription factor 4 (ATF4) is a critical transcription factor for osteoblast (OBL) function and bone formation; however, a direct role in osteoclasts (OCLs) has not been established. Here, we targeted expression of ATF4 to the OCL lineage using the Trap promoter or through deletion of Atf4 in mice. OCL differentiation was drastically decreased in Atf4-/- bone marrow monocyte (BMM) cultures and bones. Coculture of Atf4-/- BMMs with WT OBLs or a high concentration of RANKL failed to restore the OCL differentiation defect. Conversely, Trap-Atf4-tg mice displayed severe osteopenia with dramatically increased osteoclastogenesis and bone resorption. We further showed that ATF4 was an upstream activator of the critical transcription factor Nfatc1 and was critical for RANKL activation of multiple MAPK pathways in OCL progenitors. Furthermore, ATF4 was crucial for M-CSF induction of RANK expression on BMMs, and lack of ATF4 caused a shift in OCL precursors to macrophages. Finally, ATF4 was largely modulated by M-CSF signaling and the PI3K/AKT pathways in BMMs. These results demonstrate that ATF4 plays a direct role in regulating OCL differentiation and suggest that it may be a therapeutic target for treating bone diseases associated with increased OCL activity.
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What OpenQuestion holds
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.