Abstract
Early osteoarthritis (OA)-like symptoms are difficult to study owing to the lack of disease samples and animal models. In this study, we generated induced pluripotent stem cell (iPSC) lines from a patient with a radiographic early-onset finger osteoarthritis (efOA)-like condition in the distal interphalangeal joint and her healthy sibling. We differentiated those cells with similar genetic backgrounds into chondrogenic pellets (CPs) to confirm efOA. CPs generated from efOA-hiPSCs (efOA-CPs) showed lower levels of COL2A1, which is a key marker of hyaline cartilage after complete differentiation, for 21 days. Increase in pellet size and vacuole-like morphologies within the pellets were observed in the efOA-CPs. To analyze the changes occurred during the development of vacuole-like morphology and the increase in pellet size in efOA-CPs, we analyzed the expression of OA-related markers on day 7 of differentiation and showed an increase in the levels of COL1A1, RUNX2, VEGFA, and AQP1 in efOA-CPs. IL-6, MMP1, and MMP10 levels were also increased in the efOA-CPs. Taken together, we present proof-of-concept regarding disease modeling of a unique patient who showed OA-like symptoms.
Highlights
Osteoarthritis (OA) is a common form of arthritis that affects a significant portion of the elderly population worldwide
Cell lines of human induced pluripotent stem cells (hiPSCs) were generated from the isolated fibroblasts using a Sendai RNA virus to minimize the risk of genomic abnormalities
We confirmed a significant increase in the expression of hypertrophic markers in the early-onset finger osteoarthritis (efOA)-chondrogenic pellets (CPs) on day 7, which might be associated with the significant changes in the size and internal structure of the efOA-CPs
Summary
Osteoarthritis (OA) is a common form of arthritis that affects a significant portion of the elderly population worldwide. OA can affect any joint in the human body; hands, knees, or hips are most commonly affected by the disease. While in vitro disease modeling is used as a tool to study the mechanisms of cartilage-related diseases, primary chondrocytes are difficult to obtain, and they lose their phenotype and characteristics under culture conditions. These challenges can be overcome using human induced pluripotent stem cells (hiPSCs), a breakthrough in experimental modeling of human diseases [4]. Modeling of cartilage and cartilage-related diseases such as rheumatoid arthritis and knee OA have been studied using hiPSCs [1,7,8].
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