ArticleAmerican journal of translational research2017
Intermittent activation of notch signaling promotes bone formation.
Article in American journal of translational research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Benefits and Implications of Resveratrol Supplementation on Microbiota Modulations: A Systematic Review of the Literature.International journal of molecular sciences · 2022Pooled it
- Advancements in bone organoids: perspectives on construction methodologies and application strategies.Journal of advanced research · 2026Review
- DAPT Mitigates Osteoarthritic Cartilage Degeneration and Enhances Articular Repair Through Targeted Modulation of the Gucy1a3 and Notch Signaling Axis.Drug design, development and therapy · 2026Article
- Synergistic Crosstalk of PACAP and Notch Signaling Pathways in Bone Development.International journal of molecular sciences · 2025Article
- Endothelial-mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through Notch signaling.Cell communication and signaling : CCS · 2025Article
- Communication between endothelial cells and osteoblasts in regulation of bone homeostasis: Notch players.Stem cell research & therapy · 2025Review
- Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review.Frontiers in genetics · 2024Review
- [Study on the protective effect of sodium valproic acid on carbonyl cyanide 3-chlorophenylhydrazone-induced oxidative stress injury in osteoblasts].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2023Article
- Scrutinizing the Therapeutic Promise of Purinergic Receptors Targeting Depression.Neurotoxicity research · 2022Review
- Resveratrol Prevents Cytoarchitectural and Interneuronal Alterations in the Valproic Acid Rat Model of Autism.International journal of molecular sciences · 2022Article
- Signaling network regulating osteogenesis in mesenchymal stem cells.Journal of cell communication and signaling · 2022Review
- Cysteamine affects skeletal development and impairs motor behavior in zebrafish.Frontiers in pharmacology · 2022Article
- Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats.Journal of materials science. Materials in medicine · 2021Article
- Total glycosides from Eucommia ulmoides seed promoted osteogenic differentiation of adipose-derived mesenchymal stem cells and bone formation in ovariectomized rats through regulating Notch signaling pathway.Journal of orthopaedic surgery and research · 2021Article
- Context-Specific Osteogenic Potential of Mesenchymal Stem Cells.Biomedicines · 2021Article
- Thm2 interacts with paralog, Thm1, and sensitizes to Hedgehog signaling in postnatal skeletogenesis.Cellular and molecular life sciences : CMLS · 2021Article
- The interaction of Notch and Wnt signaling pathways in vertebrate regeneration.Cell regeneration (London, England) · 2021Review
- Relevance of Notch Signaling for Bone Metabolism and Regeneration.International journal of molecular sciences · 2021Review
- Modulation of Notch1 signaling regulates bone fracture healing.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020Article
- Epidrugs: novel epigenetic regulators that open a new window for targeting osteoblast differentiation.Stem cell research & therapy · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stimulatory and inhibitory effects of Notch signaling pathway on osteogenesis were both widely reported, questioning the effectiveness of small molecules targeting the Notch pathway for prevention or treatment of bone loss diseases. Here we showed that Notch signaling is activated in osteocytes embedded within the mineralized matrix and in late stages of bone marrow mesenchymal cell osteogenic cultures. Inhibition of Notch signaling markedly reduced mineralization activities of bone marrow mesenchymal cells and inhibited expressions of mineralization-associated genes when Notch ligand Jagged1 was conditionally deleted, confirming the essential roles of Notch signaling in mineralization stages of osteoblast differentiation. Moreover, intermittent activation of Notch signaling showed significant increases of bone formation in mice, rats and ovariectomized rats. A two-phase action model of Notch signaling in osteogenesis is proposed, where activation of Notch signaling in early stages of osteoblast differentiation results in proliferation of immature preosteoblast lineage cells and activation in late stages promotes differentiation of osteoblasts into osteocytes. Moreover, valproic acid is a strong activator of Notch signaling, and yearly administration of valproic acid daily showed little side effects, indicating that long term and intermittent activation of Notch signaling will be a safe and ideal way to promote anabolic bone formation for treatment of osteoporosis. Therefore, Notch signaling pathway is a good therapeutic target for bone loss diseases, and valproic acid, resveratrol and other Notch activators are promising therapeutic molecules for promoting anabolic bone formation when administered intermittently.
Indexed as
Identifiers
28670381PMC5489893W2729165583What 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.