Keywords
Osteoarthritis; Lubricin; Cartilage; Chondrocytes; High-throughput; Drug Screen
Abstract
Current therapy for arthritis predominantly focuses on the symptoms rather than the underlying causes of disease progression. Thus, it is necessary to identify novel drugs which target the underlying molecular basis of such diseases. Using high-throughput cell-based drug screening, we screened 458 different compounds, narrowed down from 811 starting compounds from the NIH Mechanistic Set. We selected drugs from the Mechanistic Set following Lipinski's Rule of 5 to ensure optimal pharmacokinetic properties. The study used modified primary human chondrocytes (IIAM-PRG4Luc), which secrete a lubricin promoter-driven luciferase reporter. We use this luciferase expression as a proxy to measure lubricin, a compound that reduces friction between articular cartilage. These cells were grown and tested in a physioxic (5% oxygen) condition which has been shown to better model joint conditions within the body as opposed to typical tissue culture in atmospheric oxygen (20%). Cells formed cartilage aggregates (5000 cells) in 384 well plates with positive and negative controls. The drugs were diluted in cell media to 2µM and fed to cells 10 times over 21 days (3 weeks). The cells were imaged two times a week to track chondrogenesis. This assay was repeated in 96 well plates with the 8 hits we found in the 384 well assay. The aggregates were then tested for lubricin, fixed, and sectioned for histology and staining. We hope to identify a compound that may improve cartilage's structural and tensile features and be a potential disease-modifying therapeutic for cartilagerelated diseases.
Thesis Completion Year
2025
Thesis Completion Semester
Summer
Thesis Chair
Kean, Thomas
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Medicine
Language
English
Access Status
Open Access
Length of Campus Access
None
Campus Location
Orlando (Main) Campus
STARS Citation
Vijayakumar, Janapriya, "High-Throughput Drug Screening For Disease-Modifying Arthritis Therapy" (2025). Honors Undergraduate Theses. 386.
https://stars.library.ucf.edu/hut2024/386
Included in
Medical Pharmacology Commons, Orthopedics Commons, Pharmaceutics and Drug Design Commons, Skin and Connective Tissue Diseases Commons
Rights Statement
