Poster # 088, Stanford University
Investigating Integrin αvβ5 Expression in Osteoarthritic Cartilage Cells
Mentors: Tamaghna Gupta, PhD and Nidhi Bhutani, PhD
Cells use integrins as primary transmembrane receptors to bind to the extracellular matrix (ECM). These receptors serve as dynamic bridges, transmitting biophysical and biochemical signals from the ECM to influence cell behavior, such as differentiation and migration. Although integrins are essential for cellular functions, altered integrin expression can drive abnormal ECM remodeling and tissue degeneration. Recently, a multijoint transcriptomic study revealed elevated integrin β5 gene expression in knee cartilage from patients with osteoarthritis (OA). However, the spatial distribution of activated integrin β5 in osteoarthritic cartilage tissue remains unknown. This spatial information is essential for identifying cells with elevated integrin β5 activation and analyzing the surrounding ECM to better understand the underlying mechanisms. In this project, we used immunofluorescence to examine and quantify the spatial expression and intensity of integrin β5, dimerized with integrin αv (αvβ5), in OA human cartilage explant sections across three different patient samples. Our results demonstrate heterogeneous expression of integrin αvβ5 among the cartilage cells. An average of ~15% of cells showed high αvβ5 expression, ~20% exhibited intermediate expression, and ~65% exhibited low expression. Additionally, we observed differences in the subcellular localization of the integrin heterodimer among cartilage cells, suggesting distinct downstream signaling pathways in these cells. Clustered αvβ5 localization at the plasma membrane indicates strong adhesion sites, whereas the sequestration of integrins in the cytoplasm is a key step in integrin trafficking, which is known to regulate cellular functions. Overall, our study demonstrates that diseased cartilage cells exhibit heterogeneous integrin αvβ5 expression, potentially linked to their role in OA progression. Identifying the integrin αvβ5-high cell population will be essential for mechanistic research that could drive the development of cell-targeted therapies for OA.