Simulation of Cartilage Damage in Osteoarthritis Using Patient-Derived Induced Pluripotent Stem Cells

Seung Min Jung¹, Yoojun Nam², Yeri Alice Rim², Yong-Beom Park¹, Seung-Ki Kwok³, Sung-Hwan Park⁴ and Ji Hyeon Ju⁵, ¹Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea, ²Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea, The Republic of, ³[email protected], Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ⁴Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea, ⁵Division of Rheumatology, Department of Internal Medicine,, College of Medicine, The Catholic University of Korea, Seoul, South Korea

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: cartilage, Osteoarthritis, pathogenesis and stem cells

Session Information

Date: Tuesday, November 15, 2016

Title: Biology and Pathology of Bone and Joint - Poster I

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Osteoarthritis (OA) is a degenerative joint disease, leading to pain and functional limitation. Although OA is a most common form of musculoskeletal disease, the pathogenesis still remains to be determined. This study was aimed to investigate the characteristics of cartilage derived from OA-iPSCs.

Methods: Dermal fibroblasts were obtained from one patient with early onset OA (age=31) and a healthy sibling without OA under informed consent. OA-iPSCs and control-iPSCs were reprogrammed from dermal fibroblasts, and differentiated into chondrocytes using outgrowth cells extending from embryoid bodies. The expression of cartilage specific markers was determined by immunohistochemical staining and reverse transcription-polymerase chain reaction (RT-PCR). To simulate the inflammatory condition of OA, chondrocytes differentiated from iPSCs were cultured in the presence of interleukin-1α.

Results: Dermal fibroblasts of OA patient and a healthy sibling were successfully reprogrammed into iPSCs. Pluripotency of OA-iPSCs and control-iPSCs was confirmed by immunohistochemical staining and RT-PCR for Nanog, Oct4, Fox2, and other pluripotent markers. All iPSCs were efficiently differentiated into cartilaginous pellet, which exhibit the chondrocyte-specific markers. Cartilage from OA-iPSCs showed an impaired mechanical integrity with porous structures. The expression of collagen type II were significantly decreased in OA-iPSC-cartilage, compared to control-iPSC-cartilage. Treatment of IL-1α enhanced the loss of cartilage, and the expression of matrix metalloproteinases and inflammatory molecules, in OA-iPSC-cartilage.

Conclusion: This study presented the impaired function of cartilage differentiated from OA patient derived iPSCs, and the simulation of cartilage damage in inflammatory condition of OA. Disease modeling of OA using patient-derived iPSCs would provide the better understanding for OA pathogenesis.

Disclosure: S. M. Jung, None; Y. Nam, None; Y. A. Rim, None; Y. B. Park, None; S. K. Kwok, None; S. H. Park, None; J. H. Ju, None.

To cite this abstract in AMA style:

Jung SM, Nam Y, Rim YA, Park YB, Kwok SK, Park SH, Ju JH. Simulation of Cartilage Damage in Osteoarthritis Using Patient-Derived Induced Pluripotent Stem Cells [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/simulation-of-cartilage-damage-in-osteoarthritis-using-patient-derived-induced-pluripotent-stem-cells/. Accessed .

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