A novel terminal differentiation model of human articular chondrocytes in three-dimensional cultures mimicking chondrocytic changes in osteoarthritis

Authors

  • Mei-Ling Ho,

    1. Department of Physiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Je-Ken Chang,

    1. Department of Orthopaedics, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Orthopedics, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Shun-Cheng Wu,

    1. Department of Physiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Ya-Hui Chung,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chung-Hwan Chen,

    1. Department of Orthopaedics, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Orthopedics, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Shao-Hung Hung,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Biological Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
    3. Department of Orthopaedic Surgery, Fooyin University Hospital, Ping-Tung County, Taiwan
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  • Gwo-Jaw Wang

    Corresponding author
    1. Department of Orthopaedics, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Orthopedics, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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Corresponding author. Department of Orthopaedics, School of Medicine, Kaohsiung Medical University, No. 100, Shih-Chuan 1st Road, Kaohsiung 807, Taiwan. Tel.: +886 7 3121101x2553; fax: +886 7 3219452. gwojaw@cc.kmu.edu.tw

Abstract

This study establishes a cell culture model mimicking the terminal differentiation occurring in osteoarthritic chondrocytes. Normal articular chondrocytes obtained from human knees treated with 5-azacytidine (Aza-C) were harvested 3, 7 and 14 days after treatment. Phenotypic and genetic changes of articular chondrocytes were detected. The results show that mRNA expression of collagen type II, a marker for normal functional articular chondrocytes, was significantly decreased after Aza-C treatment in comparison to the control cultures, while those of collagen type X and ALP, markers for hypertrophic chondrocytes, were significantly increased. Cell size and apoptotic rate of articular chondrocytes showed significant increases compared to the control after 14 days of Aza-C treatment. Terminal differentiation is shown by this model of three-dimensional cultured human articular chondrocytes, which could apply to the studies of the cellular mechanisms of osteoarthritis.

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