PUBLICATION
Notch signaling enhances bone regeneration in the zebrafish mandible
- Authors
- Kraus, J.M., Giovannone, D., Rydzik, R., Balsbaugh, J.L., Moss, I.L., Schwedler, J.L., Bertrand, J.Y., Traver, D., Hankenson, K.D., Crump, J.G., Youngstrom, D.W.
- ID
- ZDB-PUB-220219-16
- Date
- 2022
- Source
- Development (Cambridge, England) 149(5): (Journal)
- Registered Authors
- Traver, David
- Keywords
- Bone, Fracture Healing, Notch Signaling, Osteoblasts, Regeneration, Zebrafish
- MeSH Terms
-
- Animals
- Bone Regeneration
- Bony Callus/metabolism
- Fracture Healing*/physiology
- Mammals
- Mandible
- Zebrafish*
- PubMed
- 35178545 Full text @ Development
Citation
Kraus, J.M., Giovannone, D., Rydzik, R., Balsbaugh, J.L., Moss, I.L., Schwedler, J.L., Bertrand, J.Y., Traver, D., Hankenson, K.D., Crump, J.G., Youngstrom, D.W. (2022) Notch signaling enhances bone regeneration in the zebrafish mandible. Development (Cambridge, England). 149(5).
Abstract
Loss or damage to the mandible due to trauma, treatment of oral malignancies, and other diseases is treated using bone grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to mandibular bone, offering an opportunity to understand how to boost intrinsic healing potential. Using a novel her6:mCherry Notch reporter, we show that canonical Notch signaling is induced during the initial stages of cartilage callus formation in both mesenchymal cells and chondrocytes following surgical mandibulectomy. We also show that modulation of Notch signaling dose during the initial postoperative period results in lasting changes to regenerate bone quantity one month later. Pharmacological inhibition of Notch signaling reduces the size of the cartilage callus and delays its conversion into bone, resulting in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates conversion of the cartilage callus into bone, improving bone healing. Given conserved functions of this pathway in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing in mammals may both augment the size of the initial callus and boost its ossification into reparative bone.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping