ArticleThe Journal of biological chemistry2012
Transforming growth factor β suppresses osteoblast differentiation via the vimentin activating transcription factor 4 (ATF4) axis.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 61 citations in OpenAlex.
- Advances in the mechanism for steroid-induced osteonecrosis of the femoral head.Bone research · 2026Review
- Dose-Dependent Effects of TGF-β Inhibition on Osteoblast Differentiation and Wound Healing.Current issues in molecular biology · 2025Article
- Cell signaling and transcriptional regulation of osteoblast lineage commitment, differentiation, bone formation, and homeostasis.Cell discovery · 2024Review
- Switch of ELF3 and ATF4 transcriptional axis programs the amino acid insufficiency-linked epithelial-to-mesenchymal transition.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis.Endocrinology and metabolism (Seoul, Korea) · 2023Article
- Accelerated Bone Loss in Transgenic Mice Expressing Constitutively Active TGF-β Receptor Type I.International journal of molecular sciences · 2023Article
- Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women.Diagnostics (Basel, Switzerland) · 2022Article
- Review
- MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm.Cell death and differentiation · 2021Article
- Osteoclastogenic Potential of Tissue-Engineered Periosteal Sheet: Effects of Culture Media on the Ability to Recruit Osteoclast Precursors.International journal of molecular sciences · 2021Article
- A Loop-Based and AGO-Incorporated Virtual Screening Model Targeting AGO-Mediated miRNA-mRNA Interactions for Drug Discovery to Rescue Bone Phenotype in Genetically Modified Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Article
- The IAP Antagonist SM-164 Eliminates Triple-Negative Breast Cancer Metastasis to Bone and Lung in Mice.Scientific reports · 2020Article
- Hop2 Interacts with ATF4 to Promote Osteoblast Differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis.Nature communications · 2019Article
- Hepatic Osteodystrophy-Molecular Mechanisms Proposed to Favor Its Development.International journal of molecular sciences · 2019Review
- Article
- Reducing Smad3/ATF4 was essential for Sirt1 inhibiting ER stress-induced apoptosis in mice brown adipose tissue.Oncotarget · 2017Article
- Vimentin is important in the neural differentiation of PC12 cells promoted by sialylation.Glycoconjugate journal · 2017Article
- Immunology of Gut-Bone Signaling.Advances in experimental medicine and biology · 2017Article
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 2 institutions in 1 country.
Funding
Abstract
ATF4 is an osteoblast-enriched transcription factor of the leucine zipper family. We recently identified that vimentin, a leucine zipper-containing intermediate filament protein, suppresses ATF4-dependent osteocalcin (Ocn) transcription and osteoblast differentiation. Here we show that TGFβ inhibits ATF4-dependent activation of Ocn by up-regulation of vimentin expression. Osteoblasts lacking Atf4 (Atf4(-/-)) were less sensitive than wild-type (WT) cells to the inhibition by TGFβ on alkaline phosphatase activity, Ocn transcription and mineralization. Importantly, the anabolic effect of a monoclonal antibody neutralizing active TGFβ ligands on bone in WT mice was blunted in Atf4(-/-) mice. These data establish that ATF4 is required for TGFβ-related suppression of Ocn transcription and osteoblast differentiation in vitro and in vivo. Interestingly, TGFβ did not directly regulate the expression of ATF4; instead, it enhanced the expression of vimentin, a negative regulator of ATF4, at the post-transcriptional level. Accordingly, knockdown of endogenous vimentin in 2T3 osteoblasts abolished the inhibition of Ocn transcription by TGFβ, confirming an indirect mechanism by which TGFβ acts through vimentin to suppress ATF4-dependent Ocn activation. Furthermore, inhibition of PI3K/Akt/mTOR signaling, but not canonical Smad signaling, downstream of TGFβ, blocked TGFβ-induced synthesis of vimentin, and inhibited ATF4-dependent Ocn transcription in osteoblasts. Thus, our study identifies that TGFβ stimulates vimentin production via PI3K-Akt-mTOR signaling, which leads to suppression of ATF4-dependent Ocn transcription and osteoblast differentiation.
Indexed as
Identifiers
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.