Pharmacologic targeting of β-catenin improves fracture healing in old mice

β-catenin protein needs to be precisely regulated for effective fracture repair. The pace of fracture healing slows with age, associated with a transient increase in β-catenin during the initial phase of the repair process. Here we examined the ability of pharmacologic agents that target β-catenin to improve the quality of fracture repair in old mice. 20 month old mice were treated with Nefopam or the tankyrase inhibitor XAV939 after a tibia fracture. Fractures were examined 21 days later by micro-CT and histology, and 28 days later using mechanical testing. Daily treatment with Nefopam for three or seven days but not ten days improved the amount of bone present at the fracture site, inhibited β-catenin protein level, and increased colony forming units osteoblastic from bone marrow cells. At 28 days, treatment increased the work to fracture of the injured tibia. XAV939 had a more modest effect on β-catenin protein, colony forming units osteoblastic, and the amount of bone at the fracture site. This data supports the notion that high levels of β-catenin in the early phase of fracture healing in old animals slows osteogenesis, and suggests a pharmacologic approach that targets β-catenin to improve fracture repair in the elderly.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Scientific reports - 9(2019), 1 vom: 21. Juni, Seite 9005

Sprache:

Englisch

Beteiligte Personen:

Kwak, Yoon Hae [VerfasserIn]
Barrientos, Tomasa [VerfasserIn]
Furman, Bridgette [VerfasserIn]
Zhang, Hazel [VerfasserIn]
Puviindran, Vijitha [VerfasserIn]
Cutcliffe, Hattie [VerfasserIn]
Herfarth, Jonas [VerfasserIn]
Nwankwo, Eugene [VerfasserIn]
Alman, Benjamin A [VerfasserIn]

Links:

Volltext

Themen:

4UP8060B7J
Analgesics, Non-Narcotic
Beta Catenin
EC 2.4.2.30
Heterocyclic Compounds, 3-Ring
Journal Article
Nefopam
Research Support, N.I.H., Extramural
Tankyrases
XAV939

Anmerkungen:

Date Completed 26.10.2020

Date Revised 09.01.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41598-019-45339-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM298419823