ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2016
Alcohol-related deficient fracture healing is associated with activation of FoxO transcription factors in mice.
Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Modern Approaches and Emerging Biological Therapies to Treat Fracture Nonunion.Pharmaceutics · 2025Review
- Review
- New developments on the effects of alcohol use on immunity, inflammation and organ function: A summary of the 2024 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2025Article
- A single acute alcohol intoxication before fracture insult causes long-term elevated systemic RANKL and OPG levels in young adult mice.Scientific reports · 2025Article
- Chronic heavy alcohol consumption impairs the ability of demineralized allogenic bone matrix to support osteoinduction in alcohol-naïve rats.Bone reports · 2025Article
- New insights into the mechanism of alcohol-mediated organ damage via its impact on immunity, metabolism, and repair pathways: A summary of the 2021 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2022Review
- Episodic alcohol exposure attenuates mesenchymal stem cell chondrogenic differentiation during bone fracture callus formation.Alcoholism, clinical and experimental research · 2022Article
- Understanding Reactive Oxygen Species in Bone Regeneration: A Glance at Potential Therapeutics and Bioengineering Applications.Frontiers in bioengineering and biotechnology · 2022Review
- Ethanol Alters Phenotype and Synthesis Activity of Rat Neonatal Articular Chondrocytes Grown in 2- and 3-Dimensional Culture.Cartilage · 2021Article
- Impact of Alcohol on Bone Health, Homeostasis and Fracture repair.Current pathobiology reports · 2020Article
- Ethanol Inhibits Mesenchymal Stem Cell Osteochondral Lineage Differentiation Due in Part to an Activation of Forkhead Box Protein O-Specific Signaling.Alcoholism, clinical and experimental research · 2020Article
- Article
- Summary of the 2018 Alcohol and Immunology Research Interest Group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2019Review
- Exon level machine learning analyses elucidate novel candidate miRNA targets in an avian model of fetal alcohol spectrum disorder.PLoS computational biology · 2019Article
- Molecular pathogenesis of fracture nonunion.Journal of orthopaedic translation · 2018Review
- N-Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol-Fed Rats.Alcoholism, clinical and experimental research · 2018Article
- Effects of Episodic Alcohol Exposure on BMP2 Signaling During Tibia Fracture Healing.Journal of orthopaedic trauma · 2018Article
- Alcohol exposure decreases osteopontin expression during fracture healing and osteopontin-mediated mesenchymal stem cell migration in vitro.Journal of orthopaedic surgery and research · 2018Article
- Transcriptional Mechanisms of Secondary Fracture Healing.Current osteoporosis reports · 2018Review
- Partial Protection by Dietary Antioxidants Against Ethanol-Induced Osteopenia and Changes in Bone Morphology in Female Mice.Alcoholism, clinical and experimental research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The process of fracture healing is complex, and poor or incomplete healing remains a significant health problem. Proper fracture healing relies upon resident mesenchymal stem cell (MSC) differentiation into chondrocytes and osteoblasts, which are necessary for callus formation and ossification. Alcohol abuse is a leading contributor to poor fracture healing. Although the mechanism behind this action is unknown, excessive alcohol consumption is known to promote systemic oxidative stress. The family of FoxO transcription factors is activated by oxidative stress, and FoxO activation antagonizes Wnt signaling, which regulates mesenchymal stem cell differentiation. We hypothesize that alcohol exposure increases oxidative stress leading to deficient fracture repair by activating FoxO transcription factors within the fracture callus which disrupts chondrogenesis of mesenchymal stem cells. Our laboratory has developed an experimental model of delayed fracture union in mice using ethanol administration. We have found that ethanol administration significantly decreases external, cartilaginous callus formation, and hallmarks of endochondral ossification, and these changes are concomitant with increases in FoxO expression and markers of activation in fracture callus tissue of these mice. We were able to prevent these alcohol-induced effects with the administration of the antioxidant n-acetyl cysteine (NAC), suggesting that alcohol-induced oxidative stress produces the perturbed endochondral ossification and FoxO expression. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2106-2115, 2016.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.