Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency–induced osteoporosis

Authors

  • Nan Yang,

    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
    3. Department of Stomatology, The PLA 309th Hospital, Beijing, China
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    • NY and GW contributed equally to this work.

  • Guang Wang,

    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
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    • NY and GW contributed equally to this work.

  • Chenghu Hu,

    1. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Engineering Technology Center for Tissue Engineering of Xi'an, Shaanxi, China
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  • Yuanyuan Shi,

    1. Department of Ophthalmology, The PLA 306th Hospital, Beijing, China
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  • Li Liao,

    1. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Engineering Technology Center for Tissue Engineering of Xi'an, Shaanxi, China
    3. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
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  • Songtao Shi,

    1. Center for Craniofacial Molecular Biology, Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
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  • Yan Cai,

    1. Department of Ophthalmology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, People's China
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  • Shuli Cheng,

    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
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  • Xi Wang,

    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
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  • Yali Liu,

    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
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  • Liang Tang,

    1. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Engineering Technology Center for Tissue Engineering of Xi'an, Shaanxi, China
    3. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
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  • Yin Ding,

    Corresponding author
    1. Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    • 145 West Changle Road, Xi'an, Shaanxi 710032, People's Republic of China.
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  • Yan Jin

    Corresponding author
    1. Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi, China
    2. Engineering Technology Center for Tissue Engineering of Xi'an, Shaanxi, China
    3. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China
    • 145 West Changle Road, Xi'an, Shaanxi 710032, People's Republic of China.
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Abstract

Inflammatory cytokines, especially tumor necrosis factor α (TNF-α), have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen deficiency–induced osteoporosis, but the mechanism responsible remains poorly understood. MicroRNAs (miRNAs) have been shown to regulate MSC differentiation. Here, we identified a novel mechanism whereby TNF-α, suppressing the functional axis of a key miRNA (miR-21) contributes to estrogen deficiency–induced osteoporosis. In this study, we screened differentially expressed miRNAs in MSCs derived from estrogen deficiency-induced osteoporosis and found miR-21 was significantly downregulated. miR-21 was suppressed by TNF-α during the osteogenesis of MSCs. Furthermore, miR-21 was confirmed to promote the osteoblast differentiation of MSCs by repressing Spry1, which can negatively regulate the osteogenic differentiation of MSCs. Upregulating miR-21 partially rescued TNF-α–impaired osteogenesis of MSCs. Blocking TNF-α ameliorated the inflammatory environment and significantly enhanced bone formation with increased miR-21 expression and suppressed Spry1 expression in ovariectomized (OVX) mice. Our results revealed a novel function for miR-21 and suggested that suppressed miR-21 may contribute to impaired bone formation by elevated TNF-α in estrogen deficiency–induced osteoporosis. This study may indicate a molecular basis for novel therapeutic strategies against osteoporosis and other inflammatory bone diseases. © 2013 American Society for Bone and Mineral Research.

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