Dataset Information

Notch Signaling Enhances Bone Regeneration in the Zebrafish Mandible

ABSTRACT: Loss or damage to the mandible due to trauma, treatment of oral malignancies, and other diseases is currently treated using bone grafting techniques that suffer from numerous shortcomings and contraindications. Zebrafish naturally heal large injuries to their mandibular bone, and thus offer an opportunity to understand how to boost intrinsic healing ability. 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. We also show that modulation of Notch signaling during the initial postoperative period results in lasting changes to regenerate bone quantity one month later. Notch signaling is required for mandibular bone healing, as pharmacological inhibition of Notch signaling blocks cartilage callus formation and results in non-union. Conversely, conditional transgenic activation of Notch signaling accelerates regenerative ossification. Mechanistically, we report that postoperative Notch signaling regulates multiple phases of chondroid regeneration and patterns callus metabolic landscape. Given conserved functions of Notch signaling in bone repair across vertebrates, we propose that targeted activation of Notch signaling during the early phases of bone healing may have therapeutic value.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)

TISSUE(S): Mandible

SUBMITTER: Jeremy Balsbaugh

LAB HEAD: Jeremy L. Balsbaugh

PROVIDER: PXD027280 | Pride | 2022-03-07

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20210514_jcl_DYoungstrom_sample11_870ng.raw	Raw
	20210514_jcl_DYoungstrom_sample12_870ng.raw	Raw
	20210514_jcl_DYoungstrom_sample13_870ng.raw	Raw
	20210514_jcl_DYoungstrom_sample14_870ng.raw	Raw
	20210514_jcl_DYoungstrom_sample16_870ng.raw	Raw

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Publications

Notch signaling enhances bone regeneration in the zebrafish mandible.

Kraus Jessica M JM Giovannone Dion D Rydzik Renata R Balsbaugh Jeremy L JL Moss Isaac L IL Schwedler Jennifer L JL Bertrand Julien Y JY Traver David D Hankenson Kurt D KD Crump J Gage JG Youngstrom Daniel W DW

Development (Cambridge, England) 20220311 5

Loss or damage to the mandible caused by 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 ...[more]

PMID: 35178545

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