Date on Senior Honors Thesis

5-2020

Document Type

Senior Honors Thesis

Degree Name

B.A., B.S.

Department

Anthropology

Degree Program

College of Arts and Sciences

Author's Keywords

osteoimmunology; osteoclastogenesis; Treponema pallidum; pro-inflammatory cytokines; osteoclast

Abstract

The presence of pathogens in the human body influences the expression of pro-inflammatory cytokines by activated immune cells. These cytokines, and other factors, regulate osteoclastogenesis and osteoclast activity. Through experimental osteoimmunology, interactions between the inflammatory response and bone cell physiology may provide insight into how immune processes can be translated into the lesions or abnormalities observed in the osteological record. In this research, our objective was to determine if the cytokines produced by activated immune cells increase osteoclastogenesis and osteoclast activity. To evaluate this hypothesis, we used two main protocols, one for immune activation and one for osteoclastogenesis, that utilized peripheral blood mononuclear cells (PBMCs) from healthy donors. The results of these protocols indicated that cells exposed to Tp47, an antigen of Treponema pallidum, produce relatively more TNFα and IFNg than cells not exposed to infectious stimuli, yet osteoclastogenesis conditions exposed to Tp47 supernatants produced only slightly more osteoclasts than conditions exposed to untreated supernatants. After preliminary data, this outcome indicates that higher concentrations of TNFα and IFNg may not be connected to increased osteoclastogenesis. Further research is needed to increase the sample size, allowing for statistical analyses that control for the high inter-sample variability.

Lay Summary

The presence of pathogens in the human body influences the production of immune proteins commonly associated with inflammation. These immune proteins can regulate the generation of bone cells. Interactions between the immune and skeletal systems may provide insight into how the processes of the immune system can be translated into the abnormalities observed in skeletal samples, particularly archaeological or historical samples. In this research, our goal was to determine if proteins produced by activated immune cells increase bone cell generation and activity, ultimately affecting bone structure and function. To evaluate this, we used two main strategies: 1. stimulate immune cells by proteins from pathogen Treponema pallidum. This pathogen generates a chronic infection in humans, altering inflammation and bone structure, and 2. from same donor blood cells, generate bone cells. Ultimately, we explored how T. pallidum immune activated cells can alter the production of bone cells. The results indicated that cells exposed to T. pallidum proteins, produce relatively more inflammatory proteins than untreated cells, or cells not exposed to stimuli. Interestingly, the conditions introduced to liquids containing what was produced by T. pallidum activated immune cellsyielded only slightly more bone cells (osteoclast) when compared with conditions with bone cells that were not introduced to those liquids. This outcome indicates that these inflammatory proteins do not seem connected to increased bone cell formation. However, further research is needed to increase the sample size, allowing for statistical analyses that address the high level of difference between individual samples.

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