Dataset Information

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

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.

SUBMITTER: Rim YA

PROVIDER: S-EPMC7913990 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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

Rim Yeri Alice YA Nam Yoojun Y Park Narae N Lee Kijun K Jung Hyerin H Jung Seung Min SM Lee Jennifer J Ju Ji Hyeon JH

Cells 20210204 2

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) show ...[more]

PMID: 33557199

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Project description:OBJECTIVES:Alzheimer's disease (AD) is the most common neurodegenerative disease which is characterized by the formation of amyloid beta (A?) plaques and neurofibrillary tangles. These abnormal proteins induce disturbance in mitochondrial dynamics and defect in autophagy system. Since presenilin-1 (PS1) is a core component in ?-secretase complex, the mutations of PS1 gene cause the interference of ?-secretase activity and lead to the increased A?42 secretion. We aimed to characterize the patient-specific induced pluripotent stem cell (iPSC) line carrying PS1-S170F mutation. Furthermore, we tested whether disease-modifying drug can reduce AD pathology in the AD iPSC-derived neurons. MATERIALS AND METHODS:Mononuclear cells (MNCs) were isolated freshly from the peripheral blood of an autosomal dominant AD (ADAD) patient carrying presenilin-1 (PS1) mutation (Ser170Phe; PS1-S170F) and a cognitively normal control. We generated induced pluripotent stem cell (iPSC) lines, which were differentiated into functional cortical neurons. Then, we measured the markers indicative of AD pathogenesis using immunocytochemistry and Western blot. We also investigated the mitochondrial dynamics in the AD iPSC-derived neurons using Mito-tracker. RESULTS:We observed that both extracellular and intracellular A? levels were dramatically increased in the PS1-S170F iPSC-derived neurons, compared with the control iPSC-derived neurons. Furthermore, PS1-S170F iPSC-derived neurons showed high expression levels of p-Tau, which were detected both in the soma and neurites. The mitochondrial velocity in the PS1-S170F iPSC-derived neurons was much reduced, compared with that of the control. We also found a significant decrease of fusion-related protein Mfn1 (membrane proteins mitofusin 1) and an increase of fission-related protein DRP1 (dynamin-related protein 1) in the PS1-S170F iPSC-derived neurons. We further observed the defects of autophagy-related clearance in the PS1-S170F iPSC-derived neurons. Finally, we demonstrated the levels of A? and p-Tau can be dramatically reduced by the treatment of LY-2886721, a BACE1 inhibitor. CONCLUSIONS:Taken together, we have established and characterized the pathological features of an AD patient carrying PS1-S170F mutation using iPSC technology, which will be the first case on this mutation and this iPSC line will serve as a useful resource for studying AD pathogenesis and drug screening in the future.

Dataset Information

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

Publications

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

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