AcanCreER lacks specificity to chondrocytes and targets periosteal progenitors in the fractured callus.


Journal

Bone
ISSN: 1873-2763
Titre abrégé: Bone
Pays: United States
ID NLM: 8504048

Informations de publication

Date de publication:
01 2023
Historique:
received: 26 09 2022
revised: 19 10 2022
accepted: 24 10 2022
pmc-release: 01 01 2024
pubmed: 30 10 2022
medline: 30 11 2022
entrez: 29 10 2022
Statut: ppublish

Résumé

Aggrecan (Acan) is a large proteoglycan molecule constituting the extracellular matrix of cartilage, secreted by chondrocytes. To specifically target the chondrocyte lineage, researchers have widely used the AcanCreER mouse model. Evaluation of specificity and efficiency of recombination, requires Cre animals to be crossed with reporter mice. In order to accurately interpret data from Cre models, it is imperative to consider A) the amount of recombination occurring in cells/tissues that are not intended for targeting (i.e., non-specific expression), B) the efficiency of Cre recombination, which can depend on dose and duration of tamoxifen treatment, and C) the activation of CreER without tamoxifen induction, known as "Cre leakage." Using a highly sensitive reporter mouse (Ai9, tdTomato), we performed a comprehensive analysis of the AcanCreER system. Surprisingly, we observed expression in cells within the periosteum. These cells expand at a stage when chondrocytes are not yet present within the forming callus tissue (Acan/Ai9

Identifiants

pubmed: 36309308
pii: S8756-3282(22)00276-9
doi: 10.1016/j.bone.2022.116599
pmc: PMC9832919
mid: NIHMS1860021
pii:
doi:

Substances chimiques

Tamoxifen 094ZI81Y45

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

116599

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR055607
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR070813
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest None.

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Auteurs

Sanja Novak (S)

Department of Reconstructive Sciences, UConn Health, Farmington, CT, USA.

Ivo Kalajzic (I)

Department of Reconstructive Sciences, UConn Health, Farmington, CT, USA. Electronic address: ikalaj@uchc.edu.

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Classifications MeSH