DOI
https://doi.org/10.25772/47Z2-NN43
Defense Date
2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Biomedical Engineering
First Advisor
Henry J. Donahue, Ph.D.
Second Advisor
Barbara D. Boyan, Ph.D.
Third Advisor
René Olivares-Navarrete, D.D.S., Ph.D.
Fourth Advisor
Aron H. Lichtman, Ph.D.
Fifth Advisor
Jolene J. Windle, Ph.D.
Abstract
Disuse-induced bone loss is experienced by individuals that undergo prolonged bed rest, immobilization due to paralysis or injury, pregnancy, and exposure to extreme environments, such as the microgravity of space. Without therapeutic intervention, these individuals will experience decreased bone mineral density and bone quality, increasing the risk of fracture and the development of osteoporosis. Current therapeutics to mitigate bone loss include resistive exercise, anti-resorptive drugs, such as Denosumab, and anabolic agents, such as intermittent parathyroid hormone treatment. However, these therapeutics only provide limited improvement, creating a need to investigate alternative therapeutic targets, such as the endocannabinoid system (ECS). The ECS plays a significant role in regulating bone metabolism. However, the exact role of the ECS on bone varies depending on age, sex, genotype, and experimental conditions. Our preliminary data indicate that endocannabinoid receptor 1(CB1) expression in mice is protective against disuse-induced bone loss. In all, CB1 plays a role in bone metabolism, however, the mechanism by which this occurs, and the involvement of osteocytes, is not known.
We investigated the hypothesis that the expression, therefore activation, of CB1 is protective against disuse-induced bone loss. We used in vivo models to determine the role CB1 plays in osteocytic signaling during mechanical disuse and if CB1 deficiency results in a sex-dependent phenotype (bone loss in response to disuse). By addressing this gap in knowledge, we may uncover a novel therapeutic target for the treatment and prevention of unloading induced bone loss.
Rights
© Rachel C. DeNapoli
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
12-12-2023
Included in
Biomechanics and Biotransport Commons, Other Biomedical Engineering and Bioengineering Commons