ArticleBone2021
JAGGED1 stimulates cranial neural crest cell osteoblast commitment pathways and bone regeneration independent of canonical NOTCH signaling.
Article in Bone, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- CSF1R+ macrophage and osteoclast depletion impairs neural crest proliferation and craniofacial morphogenesis.Development (Cambridge, England) · 2026Article
- Ectodysplasin-A (EDA) Signaling Cross-Talk in Skeletogenesis.Calcified tissue international · 2026Review
- Regulation of Skeletogenic Pathways by m6A RNA Modification: A Comprehensive Review.Calcified tissue international · 2025Review
- The Therapeutic Potential of Melatonin in Alzheimer's Disease: A Comprehensive Review.Current medicinal chemistry · 2025Review
- Enhanced osteogenic potential of iPSC-derived mesenchymal progenitor cells following genome editing of GWAS variants in the RUNX1 gene.Bone research · 2024Article
- Article
- The Hippo signalling pathway in bone homeostasis: Under the regulation of mechanics and aging.Cell proliferation · 2024Review
- 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
- Polarity and migration of cranial and cardiac neural crest cells: underlying molecular mechanisms and disease implications.Frontiers in cell and developmental biology · 2024Review
- Biomedical engineering approaches for the delivery of JAGGED1 as a potential tissue regenerative therapy.Frontiers in bioengineering and biotechnology · 2023Review
- Molecular Signature of Neuroinflammation Induced in Cytokine-Stimulated Human Cortical Spheroids.Biomedicines · 2022Article
- Notch signaling enhances bone regeneration in the zebrafish mandible.Development (Cambridge, England) · 2022Article
- Gene regulatory network from cranial neural crest cells to osteoblast differentiation and calvarial bone development.Cellular and molecular life sciences : CMLS · 2022Review
- Regulation and Role of Transcription Factors in Osteogenesis.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Craniofacial bone loss is a complex clinical problem with limited regenerative solutions. Currently, BMP2 is used as a bone-regenerative therapy in adults, but in pediatric cases of bone loss, it is not FDA-approved due to concerns of life-threatening inflammation and cancer. Development of a bone-regenerative therapy for children will transform our ability to reduce the morbidity associated with current autologous bone grafting techniques. We discovered that JAGGED1 (JAG1) induces cranial neural crest (CNC) cell osteoblast commitment during craniofacial intramembranous ossification, suggesting that exogenous JAG1 delivery is a potential craniofacial bone-regenerative approach. In this study, we found that JAG1 delivery using synthetic hydrogels containing O9-1 cells, a CNC cell line, into critical-sized calvarial defects in C57BL/6 mice provided robust bone-regeneration. Since JAG1 signals through canonical (Hes1/Hey1) and non-canonical (JAK2) NOTCH pathways in CNC cells, we used RNAseq to analyze transcriptional pathways activated in CNC cells treated with JAG1 ± DAPT, a NOTCH-canonical pathway inhibitor. JAG1 upregulated expression of multiple NOTCH canonical pathway genes (Hes1), which were downregulated in the presence of DAPT. JAG1 also induced bone chemokines (Cxcl1), regulators of cytoskeletal organization and cell migration (Rhou), signaling targets (STAT5), promoters of early osteoblast cell proliferation (Prl2c2, Smurf1 and Esrra), and, inhibitors of osteoclasts (Id1). In the presence of DAPT, expression levels of Hes1 and Cxcl1 were decreased, whereas, Prl2c2, Smurf1, Esrra, Rhou and Id1 remain elevated, suggesting that JAG1 induces osteoblast proliferation through these non-canonical genes. Pathway analysis of JAG1 + DAPT-treated CNC cells revealed significant upregulation of multiple non-canonical pathways, including the cell cycle, tubulin pathway, regulators of Runx2 initiation and phosphorylation of STAT5 pathway. In total, our data show that JAG1 upregulates multiple pathways involved in osteogenesis, independent of the NOTCH canonical pathway. Moreover, our findings suggest that JAG1 delivery using a synthetic hydrogel, is a bone-regenerative approach with powerful translational potential.
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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.