Date of Award

6-6-2016

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2016.

Department

Bioengineering

First Advisor

Prashanth Asuri

Abstract

In recent years, much attention has been given to the effects of radiation on bone deterioration. Past research has demonstrated that radiation acts to alter the balance between osteoblasts and osteoclasts, promoting a net osteoclastic activity in the affected bone tissue, but specific molecular mechanisms remain unknown. Gene expression of many osteoclast markers is upregulated early in response to radiation, leading to bone resorption. This problem is especially prominent in space, as astronauts are regularly exposed to full body ionizing radiation that, over extended periods of time, may lead to significant bone loss. Research suggests that radiation leads to an inflammatory response in bone tissue, which leads to oxidative stress damage and increased osteoclast activity. Numerous natural compounds have been studied in vitro and have been observed to reduce the gene expression of bone resorption genes and their protein derivatives. We have attempted to take a closer look at the mechanisms by which radiation impairs bone health by examining the microarchitecture of mouse bones and the gene expression of osteoclast, osteoblast, and osteocyte markers. Much research has been devoted to studying osteoclastic activity because this is believed to play the most influential role in bone loss. Our gene expression findings show that radiation increases bone resorption and oxidative stress. Oxidative damage analysis indicated a higher level of malondialdehyde (MDA) in the irradiated, control diet samples compared to non-irradiated mice on the control diet and suggested that dried plum may protect bones by a systemic reduction in oxidative damage. Physical characterization results that we obtained from microCT demonstrate that a dried plum diet increased the bone mass compared to the control diet, but failed to show an effect from radiation on bone. The microCT data collected is not sufficient to confirm that dried plum has a radio-protective effect in vertebrae. Although at this stage, we have limited data to fully understand the mechanisms by which dried plum protects bone, we show that dried plum can increase bone mass in vertebrae and systemically reduces MDA levels in circulation. Our research increases the current medical and biological understanding of bone physiology in response to radiation and proposed dietary countermeasures, and is of relevance to astronauts in extended space missions, cancer patients, and patients with osteoporosis.

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