Publication Date
12-2023
Date of Final Oral Examination (Defense)
10-12-2023
Type of Culminating Activity
Dissertation
Degree Title
Doctor of Philosophy in Materials Science and Engineering
Department Filter
Materials Science and Engineering
Department
Materials Science and Engineering
Supervisory Committee Chair
Gunes Uzer, Ph.D.
Supervisory Committee Member
Julia Oxford, Ph.D.
Supervisory Committee Member
Sarah Manske, Ph.D.
Supervisory Committee Member
David Estrada, Ph.D.
Abstract
As the global population ages and life expectancy continues to rise, osteoporosis continues to be a growing worldwide health concern. The International Osteoporosis Foundation reports 1 in 3 women over the age of 50 years and 1 in 5 men worldwide will experience osteoporotic fractures in their lifetime, costing between 5 and 6.5 trillion USD annually in Canada, Europe, and the United States alone. The need for preventative measures to reduce age-related bone loss is clear, not only to improve quality of life for countless individuals but also to relieve the economic burden this condition imposes.
Exercise is a proven preventative method as it increases and maintains bone density, and reduces the risk of osteoporotic fracture with age. The benefits of exercise are not only mediated by physiological changes, but also by mechanically challenging the tissue. The work presented here seeks to elucidate how attenuating cellular mechanotransduction from embryogenesis through adolescence and into adulthood affects bone quality before and after exercise, as well as how exposure to whole-body low-intensity vibration from adulthood into old age affects bone quality before and after exercise.
Linker of Nucleoskeleton and Cytoskeleton (LINC) protein complexes play an important role in cellular structure by connecting cytoskeletal elements to the nuclear envelope, as well as being critical regulator of force transmission from the cytoskeleton to the nucleus in vitro. We hypothesized disrupting these complexes in vivo would lead to decreased bone quality outcomes. To investigate LINC function in vivo, we generated two Cre/lox murine models that disrupt the LINC complex in bone progenitor cells – one under the Prrx1 promoter and the other under the osterix (Osx) marker. Bone microarchitecture and mechanical properties were measured at an 8-week baseline old mice and mice subjected to a 6-week exercise intervention. We found decreased osteogenic and adipogenic differentiation potential of bone marrow aspirates in our Osx model as well as diminished trabecular architecture an 8-week baseline; however, there were no remarkable changes in bone microarchitecture or mechanical properties after our six-week running intervention. Similarly, our Prrx1 model did not show any bone microarchitecture or mechanical property changes after our six- week running intervention, but this model also did not show an cellular phenotype differences or 8-week baseline differences either.
Finally, to investigate how exposure to whole-body low-intensity vibration from adulthood into old age affects bone quality before and after exercise, we subjected 20-week old female C57Bl/6J mice to a low-intensity vibration (LIV) intervention (0.7g, 90Hz) for 15 minutes/2 times a day/5 days a week until they reach 48 weeks of age. A sub-cohort was placed in a six-week running intervention. We did not see any remarkable changes in bone microarchitecture or bone mechanical properties with long-term LIV treatment or exercise. Understanding the mechanical regulation of bone progenitor cells and how bone tissue responds to long-term physical stimulation in an aging population may lead to improved physiotherapy interventions, reducing the prevalence of osteoporotic fractures.
The study findings included in this text, while not groundbreaking, shed light into the complex environment of bone mechanobiology. Whole bone tissue appears to be mostly unaffected by perturbations in mechanical signaling, whether that be through LINC complex disruption or addition of vibrational signals throughout the lifespan; however, there is evidence for changes in the cellular environment which could potentially lead to bone mineral makeup differences. Future investigation into mechanical regulation of bone tissue may benefit from focusing on cell-specific adaptations or utilizing more robust mechanical challenge model for induction of whole bone tissue changes.
DOI
https://doi.org/10.18122/td.2151.boisestate
Recommended Citation
Birks, Scott Aaron, "Role of Mechanical Signaling in Bone Tissue" (2023). Boise State University Theses and Dissertations. 2151.
https://doi.org/10.18122/td.2151.boisestate