Date of Award

2016

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology, Neurobiology and Anatomy

Abstract

Proper and complete repair of a bone fracture is essential in quality of life maintenance, but poor healing and fracture malunion are still medically and socially relevant problems. Alcohol abuse impairs normal fracture healing, leading to delayed or incomplete union. This dissertation aims to clarify mechanisms behind this alcohol-induced impaired healing, thereby elucidating potential methods of intervention.

Alcohol-induced oxidative stress has been linked to many morbidities associated with alcohol abuse. This dissertation elucidates a potential mechanism through which alcohol inhibits fracture healing by increasing oxidative stress. Using a rodent model, I found that alcohol exposure decreases fracture callus formation and endochondral ossification, and these changes are associated with markers of activation of FoxO transcription factors. FoxO transcription factors are known to be activated by oxidative stress and inhibit proper mesenchymal stem cell differentiation, which is crucial in callus formation. These deleterious effects of alcohol were prevented with the administration of an antioxidant. These results begin to illuminate how alcohol abuse can negatively affect fracture healing and bone health in general, while characterizing aspects of skeletal biology that are applicable beyond alcohol-associated pathologies.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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