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Titel: Establishment of a Reliable Model to Study the Failure of Fracture Healing in Aged Mice
VerfasserIn: Menger, Maximilian M.
Laschke, Matthias W.
Scheuer, Claudia
Bauer, David
Bleimehl, Michelle
Später, Thomas
Rollmann, Mika F.
Braun, Benedikt J.
Herath, Steven C.
Raza, Ahsan
Menger, Michael D.
Histing, Tina
Sprache: Englisch
Titel: Journals of Gerontology: Biological Sciences
Bandnummer: 77 (2022)
Heft: 5
Seiten: 909-917
Verlag/Plattform: Oxford University Press
Erscheinungsjahr: 2021
Freie Schlagwörter: Aging
Fracture healing
Inflammation
Murine
Vascularization
DDC-Sachgruppe: 610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: The failure of fracture healing represents a substantial clinical problem. Moreover, aged patients demonstrate an elevated risk for failed bone healing. However, murine models to study the failure of fracture healing are established only in young adult animals. Therefore, the aim of this study was to develop a reliable model to study failed fracture healing in aged mice. After creation of a 1.8-mm segmental defect and periosteal resection, femora of aged mice (18–20 months) and young adult control mice (3–4 months) were stabilized by pin-clip fixation. Segmental defects were analyzed by means of biomechanics, x-ray, and micro-computed tomography, as well as histomorphometric, immunohistochemical, and Western blot analysis. After 10 weeks, all animals showed a complete lack of osseous bridging, resulting in fracture healing failure. Segmental defects in aged mice revealed a reduced bone formation and vascularization when compared to young adult mice. This was associated with a decreased expression of bone formation markers. In addition, we detected a reduced number of tartrate-resistant acid phosphatase-positive osteoclasts and an elevated osteoprotegerin/receptor activator of NF-ĸB ligand ratio in aged animals, indicating a reduced osteoclast activity. Moreover, aged animals showed also an enhanced inflammatory response, characterized by an increased infiltration of macrophages within the callus tissue. Taken together, we herein report for the first time a reliable model to study fracture healing failure in aged mice. In the future, the use of this model enables us to study novel therapeutic strategies and molecular mechanics of failed fracture healing during aging.
DOI der Erstveröffentlichung: 10.1093/gerona/glab304
URL der Erstveröffentlichung: https://doi.org/10.1093/gerona/glab304
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-440630
hdl:20.500.11880/39420
http://dx.doi.org/10.22028/D291-44063
ISSN: 1758-535X
1079-5006
Datum des Eintrags: 21-Jan-2025
Fakultät: M - Medizinische Fakultät
Fachrichtung: M - Chirurgie
M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professur: M - Prof. Dr. Michael D. Menger
M - Prof. Dr. Markus Meyer
M - Prof. Dr. Tim Pohlemann
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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