Characterization of Early-Onset Finger Osteoarthritis-Like Condition Using Patient-Derived Induced Pluripotent Stem Cells

Cells

Kijun Lee¹  SeungMin Jung¹  Yoojun Nam¹  Narae Park¹  JiHyeon Ju¹  Hyerin Jung¹  YeriAlice Rim¹  Jennifer Lee² 

[1] Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea;Department of Internal Medicine, Division of Rheumatology, Institute of Medical Science, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea;

关键词: chondrogenesis;    human induced pluripotent stem cell;    IL-6;    MMP1;    MMP10;   

DOI  :  10.3390/cells10020317

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown