Date of Award

2026

Document Type

Honors Thesis (Open Access)

Department

Colby College. Biology Dept.

Advisor(s)

Johanna van Oers

Second Advisor

Christina Cota

Third Advisor

Anna Forsman

Abstract

Mechanical stress plays a central role in shaping cellular behavior within skeletal tissues. At the enthesis, where tendons and ligaments attach to bone, repeated mechanical loading is strongly associated with inflammation and the development of ankylosing spondylitis (AS). Although mesenchymal stem cells (MSCs) are known to contribute to tissue structure and repair at these sites, their potential role in inflammatory signaling, particularly within the I 23/IL 17 pathway, remains unclear. In this thesis I investigated whether MSCs are capable of expressing cytokines involved in this pathway and how mechanical stress and differentiation influence this expression. Using the mouse derived C3H/10T1/2 MSC cell line, I first assessed baseline expression of IL 17A and IL 23R through PCR analysis. I then examined changes in IL 17A expression following exposure to fluid flow shear stress (FFSS) using qRT -PCR across multiple time points and in addition; I evaluated the effect of chondrogenic differentiation on IL 17A expression and compared morphological changes with published primary chondrocyte data.

I report that MSCs express IL 17A but do not express IL 23R under baseline conditions, suggesting a potential IL 23 independent mechanism of IL 17A production. Furthermore, MSCs respond to mechanical stress with a transient increase in IL 17A expression, followed by a decrease with prolonged exposure. Chondrogenic differentiation resulted in a significant reduction in IL 17A expression, indicating that IL 17A expression may be associated with a more undifferentiated cell state.

These results suggest that MSCs are not only structural cells but may also actively participate in inflammatory signaling at the enthesis. The ability of MSCs to modulate IL 17A expression in response to mechanical stress and differentiation highlights a potential link between mechanical loading, inflammation, and tissue remodeling in AS. Overall, this project provides evidence that MSC behavior is highly context dependent and may contribute to both inflammatory and regulatory processes within the enthesis, offering new insight into the complexity of MSC function in disease.

Keywords

Ankylosing Spondylitis (AS), Entheses, FFSS, IL 23/IL 17 pathway, Mesenchymal Stem cells (MSCs)

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