PPARγ silencing enhances osteogenic differentiation of human adipose-derived mesenchymal stem cells

Authors

  • Mon-Juan Lee,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Bioscience Technology, Chang Jung Christian University, Tainan, Taiwan
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    • These authors contributed equally to this work.
  • Hui-Ting Chen,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan
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    • These authors contributed equally to this work.
  • Mei-Ling Ho,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Orthopaedics, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Physiology, Kaohsiung Medical University, Kaohsiung, Taiwan
    4. Graduate Institute of Physiology and Molecular Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    5. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Chung-Hwan Chen,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Orthopaedics, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    4. Department of Sports Medicine, Faculty of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    5. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Shu-Chun Chuang,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Sung-Cheng Huang,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Yin-Chih Fu,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Orthopaedics, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    4. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Gwo-Jaw Wang,

    1. Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Department of Orthopaedics, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
    4. Department of Orthopaedic Surgery, University of Virginia, Virginia, USA
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  • Lin Kang,

    1. Department of Obstetrics and Gynaecology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan
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  • Je-Ken Chang

    Corresponding author
    1. Department of Orthopaedics, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Graduate Institute of Physiology and Molecular Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    4. Department of Orthopaedics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    5. Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
    • Orthopaedic Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan
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Correspondence to: Je-Ken CHANG, M.D., Department of Orthopaedics, Kaohsiung Municipal Ta-Tung Hospital, No. 68, Zhonghua 3rd Rd., Kaohsiung 801, Taiwan.

Tel.: +886-7-2911101 (ext. 8902)

Fax: +886-7-3219452

E-mail: jkchang@cc.kmu.edu.tw

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis, and has been indicated as a potential therapeutic target to promote osteoblast differentiation. However, recent studies suggest that suppression of PPARγ inhibits adipogenesis, but does not promote osteogenic differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs). It was reasoned that the osteogenic effect of PPARγ suppression may be masked by the strong osteogenesis-inducing condition commonly used, resulting in a high degree of matrix mineralization in both control and experimental groups. This study investigates the role of PPARγ in the lineage commitment of human adipose-derived mesenchymal stem cells (hADSCs) by interfering with the function of PPARγ mRNA through small interfering RNAs (siRNAs) specific for PPARγ2. By applying an osteogenic induction condition less potent than that used conventionally, we found that PPARγ silencing led to retardation of adipogenesis and stimulated a higher level of matrix mineralization. The mRNA level of PPARγ decreased to 47% of control 2 days after treatment with 50 nmol/l PPARγ2 siRNA, while its protein expression was 60% of mock control. In the meantime, osteogenic marker genes, including bone morphogenic protein 2 (BMP2), runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP) and osteocalcin (OC), were up-regulated under PPARγ silencing. Our results suggest that transient suppression of PPARγ promotes the onset of osteogenesis, and may be considered a new strategy to stimulate bone formation in bone tissue engineering using hADSCs.

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