Modulation of Notch1 signaling regulates bone fracture healing.
Notch signaling
alpha-smooth muscle actin
bone fracture
inducible Cre
osteoblast differentiation
periosteal progenitors
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
06
11
2019
revised:
30
01
2020
accepted:
22
02
2020
pubmed:
7
3
2020
medline:
2
2
2021
entrez:
7
3
2020
Statut:
ppublish
Résumé
Fracture healing involves interactions of different cell types, driven by various growth factors, and signaling cascades. Periosteal mesenchymal progenitor cells give rise to the majority of osteoblasts and chondrocytes in a fracture callus. Notch signaling has emerged as an important regulator of skeletal cell proliferation and differentiation. We investigated the effects of Notch signaling during the fracture healing process. Increased Notch signaling in osteochondroprogenitor cells driven by overexpression of Notch1 intracellular domain (NICD1) (αSMACreERT2 mice crossed with Rosa-NICD1) during fracture resulted in less cartilage, more mineralized callus tissue, and stronger and stiffer bones after 3 weeks. Periosteal cells overexpressing NICD1 showed increased proliferation and migration in vitro. In vivo data confirmed that increased Notch1 signaling caused expansion of alpha-smooth muscle actin (αSMA)-positive cells and their progeny including αSMA-derived osteoblasts in the callus without affecting osteoclast numbers. In contrast, anti-NRR1 antibody treatment to inhibit Notch1 signaling resulted in increased callus cartilage area, reduced callus bone mass, and reduced biomechanical strength. Our study shows a positive effect of induced Notch1 signaling on the fracture healing process, suggesting that stimulating the Notch pathway could be beneficial for fracture repair.
Identifiants
pubmed: 32141629
doi: 10.1002/jor.24650
pmc: PMC7483882
mid: NIHMS1576092
doi:
Substances chimiques
Notch1 protein, mouse
0
Receptor, Notch1
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2350-2361Subventions
Organisme : Connecticut Innovations
ID : 14-SCA-UCHC-02
Pays : International
Organisme : NIAMS NIH HHS
ID : AR070813
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055607
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070813
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR066028
Pays : United States
Organisme : Connecticut Innovations
ID : 16-RMB-UCHC-10
Pays : International
Organisme : PRORP-CDMRP
ID : OR140396
Pays : International
Organisme : NIAMS NIH HHS
ID : AR055607
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR066028
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR055607
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR066028
Pays : United States
Organisme : NIAMS NIH HHS
ID : AR070813
Pays : United States
Informations de copyright
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
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