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] |
---|
Links: |
---|
Themen: |
4UP8060B7J |
---|
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 |
---|
LEADER | 01000caa a22002652 4500 | ||
---|---|---|---|
001 | NLM298419823 | ||
003 | DE-627 | ||
005 | 20231226200300.0 | ||
007 | cr uuu---uuuuu | ||
008 | 231225s2019 xx |||||o 00| ||eng c | ||
024 | 7 | |a 10.1038/s41598-019-45339-0 |2 doi | |
028 | 5 | 2 | |a pubmed24n0994.xml |
035 | |a (DE-627)NLM298419823 | ||
035 | |a (NLM)31227757 | ||
040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
041 | |a eng | ||
100 | 1 | |a Kwak, Yoon Hae |e verfasserin |4 aut | |
245 | 1 | 0 | |a Pharmacologic targeting of β-catenin improves fracture healing in old mice |
264 | 1 | |c 2019 | |
336 | |a Text |b txt |2 rdacontent | ||
337 | |a ƒaComputermedien |b c |2 rdamedia | ||
338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
500 | |a Date Completed 26.10.2020 | ||
500 | |a Date Revised 09.01.2021 | ||
500 | |a published: Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a 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 | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, N.I.H., Extramural | |
650 | 7 | |a Analgesics, Non-Narcotic |2 NLM | |
650 | 7 | |a Heterocyclic Compounds, 3-Ring |2 NLM | |
650 | 7 | |a XAV939 |2 NLM | |
650 | 7 | |a beta Catenin |2 NLM | |
650 | 7 | |a Nefopam |2 NLM | |
650 | 7 | |a 4UP8060B7J |2 NLM | |
650 | 7 | |a Tankyrases |2 NLM | |
650 | 7 | |a EC 2.4.2.30 |2 NLM | |
700 | 1 | |a Barrientos, Tomasa |e verfasserin |4 aut | |
700 | 1 | |a Furman, Bridgette |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Hazel |e verfasserin |4 aut | |
700 | 1 | |a Puviindran, Vijitha |e verfasserin |4 aut | |
700 | 1 | |a Cutcliffe, Hattie |e verfasserin |4 aut | |
700 | 1 | |a Herfarth, Jonas |e verfasserin |4 aut | |
700 | 1 | |a Nwankwo, Eugene |e verfasserin |4 aut | |
700 | 1 | |a Alman, Benjamin A |e verfasserin |4 aut | |
773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 9(2019), 1 vom: 21. Juni, Seite 9005 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
773 | 1 | 8 | |g volume:9 |g year:2019 |g number:1 |g day:21 |g month:06 |g pages:9005 |
856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-019-45339-0 |3 Volltext |
912 | |a GBV_USEFLAG_A | ||
912 | |a GBV_NLM | ||
951 | |a AR | ||
952 | |d 9 |j 2019 |e 1 |b 21 |c 06 |h 9005 |