ArticleThe Journal of clinical investigation2014
NOTCH inhibits osteoblast formation in inflammatory arthritis via noncanonical NF-κB.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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The trial behind it
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Who cites it
59 citing papers in PubMed, 86 citations in OpenAlex.
- Notch Signalling Pathway in the Pathogenesis of Periodontitis: Research Progress.International dental journal · 2026Review
- Betulinic acid alleviates the inflammatory injury of osteoblasts in osteoporosis by augmenting autophagy via the AMPK-mTOR signaling pathway.International journal of molecular medicine · 2026Article
- Low-Intensity Pulsed Ultrasound Enhances Intramembranous Bone Healing in a Critical-Size Bone Defect of the Rat Calvaria.Journal of clinical medicine · 2026Article
- The risk of osteoporosis in COPD: An analysis of sex differences and mediating effects based on NHANES.NPJ primary care respiratory medicine · 2026Article
- Role of Notch signaling pathway in joint homeostasis and osteoarthritis.Frontiers in bioengineering and biotechnology · 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
- The Notch signaling pathway in regulating bone and cartilage homeostasis: novel insights into the pathogenesis and therapeutics of osteoarthritis.Cell communication and signaling : CCS · 2025Review
- Development of RelB-targeting small-molecule inhibitors of non-canonical NF-κB signaling with antitumor efficacy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Multifaceted Role of Notch Signaling in Vascular Health and Diseases.Biomedicines · 2025Review
- The role of growth hormone in assisted reproductive technology for patients with diminished ovarian reserve: from signaling pathways to clinical applications.Frontiers in endocrinology · 2025Review
- Article
- Another Notch in the Belt of Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Osteogenic Protection against Fine Dust with Erucic Acid-Induced Exosomes.Journal of functional biomaterials · 2024Article
- Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects.bioRxiv : the preprint server for biology · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Osteoimmunology: The Crosstalk between T Cells, B Cells, and Osteoclasts in Rheumatoid Arthritis.International journal of molecular sciences · 2024Review
- Article
- DNA methylation-mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation.The Journal of clinical investigation · 2023Article
- The role of apoptosis in the pathogenesis of osteoarthritis.International orthopaedics · 2023Review
- The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials.Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
NOTCH-dependent signaling pathways are critical for normal bone remodeling; however, it is unclear if dysfunctional NOTCH activation contributes to inflammation-mediated bone loss, as observed in rheumatoid arthritis (RA) patients. We performed RNA sequencing and pathway analyses in mesenchymal stem cells (MSCs) isolated from transgenic TNF-expressing mice, a model of RA, to identify pathways responsible for decreased osteoblast differentiation. 53 pathways were dysregulated in MSCs from RA mice, among which expression of genes encoding NOTCH pathway members and members of the noncanonical NF-κB pathway were markedly elevated. Administration of NOTCH inhibitors to RA mice prevented bone loss and osteoblast inhibition, and CFU-fibroblasts from RA mice treated with NOTCH inhibitors formed more new bone in recipient mice with tibial defects. Overexpression of the noncanonical NF-κB subunit p52 and RELB in a murine pluripotent stem cell line increased NOTCH intracellular domain-dependent (NICD-dependent) activation of an RBPjκ reporter and levels of the transcription factor HES1. TNF promoted p52/RELB binding to NICD, which enhanced binding at the RBPjκ site within the Hes1 promoter. Furthermore, MSC-enriched cells from RA patients exhibited elevated levels of HES1, p52, and RELB. Together, these data indicate that persistent NOTCH activation in MSCs contributes to decreased osteoblast differentiation associated with RA and suggest that NOTCH inhibitors could prevent inflammation-mediated bone loss.
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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.