Notch Signaling in Bone Development and Regeneration
Summary
Notch signalling is a highly conserved cell-to-cell communication pathway that orchestrates cell fate determination, proliferation and differentiation within the skeletal system. Activation occurs when membrane-bound ligands engage Notch receptors, triggering proteolytic cleavage and release of the Notch intracellular domain (NICD), which translocates to the nucleus to modulate gene transcription through RBPJκ and downstream effectors such as HES and HEY. During embryonic skeletogenesis, Notch regulates the balance between chondrogenic and osteogenic lineages, ensuring proper formation of cartilage templates and subsequent bone deposition. In postnatal life, Notch maintains bone homeostasis by fine-tuning osteoblast and osteoclast activity and contributes to fracture repair by recapitulating developmental programmes. Dysregulation of Notch signalling has been implicated in age-related bone loss, nonunion fractures and degenerative musculoskeletal disorders. Strategic modulation of the pathway holds promise for enhancing skeletal regeneration, combating osteoporosis and improving outcomes in complex bone-healing scenarios.
Research from Nature Portfolio
No recent Nature Portfolio content available.
Notch Signaling in Bone Development and Regeneration publication trend
The graph below shows the total number of articles in notch signaling in bone development and regeneration across all publications each year (not limited to Nature Index journals).
Technical terms
Notch receptor: A single-pass transmembrane protein that, upon ligand binding, releases an intracellular domain to regulate target gene transcription.
NICD (Notch intracellular domain): The cleaved fragment of the Notch receptor that enters the nucleus to activate downstream gene expression.
RBPJκ: A DNA-binding transcriptional effector that partners with NICD to regulate canonical Notch target genes.
Skeletal stem and progenitor cells (SSPCs): Bone marrow–derived cells capable of differentiating into osteoblasts, chondrocytes and adipocytes, essential for bone maintenance and repair.
Osteogenic differentiation: The process by which multipotent progenitors commit to and mature as bone-forming osteoblasts.
References
- Loss of Notch signaling in skeletal stem cells enhances bone formation with aging. Bone Research (2023).
- Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing. Experimental & Molecular Medicine (2023).
- DNA methylation mediated Rbpjk suppression protects against fracture nonunion caused by systemic inflammation. Journal of Clinical Investigation (2023).
- Insights into the Notch signaling pathway in degenerative musculoskeletal disorders: Mechanisms and perspectives. Biomedicine & Pharmacotherapy (2023).
- Notch Signaling in Skeletal Development, Homeostasis and Pathogenesis. Biomolecules (2020).
Turn complex research questions into confident strategic decisions
When you're under pressure to set direction, justify investment, or understand your competitive position, you need more than raw data — you need trusted insights you can act on.
Benchmark your performance against global peers using robust, methodologically sound analysis.
Combine quantitative metrics with qualitative expert insight to uncover strengths, gaps and emerging opportunities.
Gain tailored, decision-ready recommendations aligned to your strategic priorities.
Talk to us to learn more about our data dashboards and bespoke strategy reports.
Grow research skills, confidence and careers with training built for every stage of the research lifecycle.
Developed with Nature Portfolio journal Editors and internationally renowned experts. Discover three ways to learn:
Self-paced, online courses in convenient bite-sized units, covering key skills across scientific writing, publishing, grant writing, data analysis, and more.
Expert trainer-led workshops with hands-on exercises and real-time feedback across core research skills, delivered via interactive group sessions.
Editor-led workshops combining core principles in writing and publishing, personalised 1:1 feedback from Nature Portfolio Editors and hands-on exercises.
Explore course catalogues and workshop agendas, enquire about the options or request institutional pricing.