Keywords
chondrocyte; osteoarthritis; assay; cartilage; luciferase; lubricin
Abstract
Osteoarthritis (OA) is a degenerative disease that affects many people worldwide. Current methods of treatment are palliative, and no treatment exists to fully reverse or cure OA once it begins to progress. The discovery of a disease-modifying osteoarthritic drug (DMOAD) would increase the quality of life for millions and reduce the need for invasive procedures. Screening FDA-approved drugs ensures more promise due to their known safety profile and potential for faster translation to the clinic. The goal of this project was to conduct dose-response assays with FDA-approved drugs that have been shown to stimulate lubricin production in cells that mimic arthritic joints using a 3D model. Primary human chondrocytes modified to express a lubricin promoter-driven luciferase reporter to measure lubricin, a key component in reducing friction between articular cartilage, were thawed. Chondrocytes were grown in physioxic conditions, then formed into cartilage aggregates. Aggregates underwent a 12-day growth period, followed by a simulated injury with addition of IL-1β, then continuous stimulation with serially diluted FDA-approved compounds until the 21-day mark. Aggregates were imaged throughout. Following the assay, lubricin reporter production was quantified. Aggregates were fixed for histology as well as reserved for biochemical assays testing for DNA, glycosaminoglycans, and hydroxyproline. The goal of this project was to investigate the dose-dependent effects of selected FDA-approved compounds on lubricin expression using a 3D cartilage aggregate model, as a key step in exploring their potential as DMOADs.
Thesis Completion Year
2025
Thesis Completion Semester
Summer
Thesis Chair
Kean, Thomas
College
College of Medicine
Department
Department of Medicine
Thesis Discipline
Medicine
Language
English
Access Status
Open Access
Length of Campus Access
None
Campus Location
Orlando (Main) Campus
STARS Citation
Menon, Swathi S., "Investigation Of Lubricin-Stimulating Fda-Approved Compounds For A Disease-Modifying Osteoarthritic Drug" (2025). Honors Undergraduate Theses. 394.
https://stars.library.ucf.edu/hut2024/394
Included in
Medical Pharmacology Commons, Orthopedics Commons, Pharmaceutics and Drug Design Commons, Skin and Connective Tissue Diseases Commons
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