Melatonin enhances chondrogenic differentiation of human mesenchymal stem cells

Authors

  • Wenjie Gao,

    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this study.
  • Mianlong Lin,

    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this study.
  • Anjing Liang,

    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
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    • These authors contributed equally to this study.
  • Liangming Zhang,

    1. Department of Spine Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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  • Changhua Chen,

    1. School of Life Sciences, Sun Yat-sen University, Guangzhou, China
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  • Guoyan Liang,

    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
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  • Caixia Xu,

    1. Research Center of Translational Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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  • Yan Peng,

    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
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  • Chong Chen,

    1. Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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  • Dongsheng Huang,

    Corresponding author
    1. Department of Spine Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China
    • Address reprint requests to Peiqiang Su, Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

      E-mail: supq@mail.sysu.edu.cn

      Dongsheng Huang, Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.

      E-mail: huangdongshen18@hotmail.com

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  • Peiqiang Su

    Corresponding author
    1. Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
    • Address reprint requests to Peiqiang Su, Department of Orthopedic Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.

      E-mail: supq@mail.sysu.edu.cn

      Dongsheng Huang, Department of Orthopedic Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China.

      E-mail: huangdongshen18@hotmail.com

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Abstract

Intramembranous ossification and endochondral ossification are two ways through which bone formation and fracture healing occur. Accumulating amounts of evidence suggests that melatonin affects osteoblast differentiation, but little is known about the effects of melatonin on the process of chondrogenic differentiation. In this study, the effects of melatonin on human mesenchymal stem cells (MSCs) undergoing chondrogenic differentiation were investigated. Cells were induced along chondrogenic differentiation via high-density micromass culture in chondrogenic medium containing vehicle or 50 nm melatonin. Histological study and quantitative analysis of glycosaminoglycan (GAG) showed induced cartilage tissues to be larger and richer in GAG, collagen type II and collagen type X in the melatonin group than in the untreated controls. Real-time RT-PCR analysis demonstrated that melatonin treatment significantly up-regulated the expression of the genes involved in chondrogenic differentiation, including aggrecan (ACAN), collagen type II (COL2A1), collagen type X (COL10A1), SRY (sex-determining region Y)-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and the potent inducer of chondrogenic differentiation, bone morphogenetic protein 2 (BMP2). And the expression of melatonin membrane receptors (MT) MT1 and MT2 were detected in the chondrogenic-induced-MSCs by immunofluorescence staining. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to increase the size and GAG synthesis of the induced cartilage tissues, as well as to completely reverse the effect of melatonin on the gene expression of ACAN, COL2A1, COL10A1, SOX9 and BMP2 after 7 days of differentiation. These findings demonstrate that melatonin enhances chondrogenic differentiation of human MSCs at least partially through melatonin receptors.

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