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Real-time Bioluminescence Imaging of Notch Signaling Dynamics during Murine Neurogenesis
Published on: December 12, 2019
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Role of Notch signaling in corticalization
Gherardo Mazziotti1,2, Ernesto Canalis3
1Department of Biomedical Sciences, Humanitas, University of Milan, Pieve Emanuele-Milan, Italy.
Journal of Endocrinological Investigation
|November 1, 2025
Summary
Corticalization, the process of forming strong cortical bone, is crucial for lifelong skeletal integrity. Impaired corticalization leads to bone fragility, highlighting its importance in bone health.
Area of Science:
- Skeletal Biology
- Bone Physiology
- Developmental Biology
Background:
- Cancellous bone remodeling is well-studied, but mechanisms of cortical bone formation and homeostasis remain unclear.
- Corticalization, where trabeculae merge into cortical bone, is vital for skeletal integrity throughout life.
- Defects in cortical bone formation result in significant skeletal fragility.
Purpose of the Study:
- To investigate the mechanisms underlying cortical bone formation and homeostasis.
- To explore the role of NOTCH3 signaling in corticalization.
- To understand the link between impaired corticalization and skeletal fragility.
Main Methods:
- Utilized mouse models with genetic inactivation of key bone-related genes (Sp7, Itgb3, Socs3, Clcn7).
- Investigated Notch receptor signaling, focusing on NOTCH3.
- Analyzed mouse models expressing the active NOTCH3 intracellular domain (N3ICD) in osteoblasts and osteocytes.
Main Results:
- Mouse models with inactivated Sp7, Itgb3, Socs3, and Clcn7 showed impaired corticalization and osteopetrosis.
- Expression of active NOTCH3 intracellular domain in osteoblasts and osteocytes prevented cortical bone formation.
- These NOTCH3-expressing mice exhibited skeletal fragility, increased intracortical remodeling, and porosity.
Conclusions:
- Corticalization is an essential process for maintaining skeletal integrity with lifelong implications.
- NOTCH3 signaling appears to play a critical role in regulating cortical bone formation.
- Impaired corticalization, potentially mediated by NOTCH3, leads to skeletal fragility.
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