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CCAAT/enhancer binding protein beta is up-regulated in giant cell tumor of bone and regulates RANKL expression

Authors

  • Patrick Kwok-Shing Ng,

    1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Stephen Kwok-Wing Tsui,

    Corresponding author
    1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
    • School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR.
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  • Carol Po-Ying Lau,

    1. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Chi-Hang Wong,

    1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Winnie Hiu-Ting Wong,

    1. School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Lin Huang,

    1. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
    2. Department of Surgery, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Shekhar-Madhukar Kumta

    1. Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR
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  • Patrick Kwok-Shing Ng and Stephen Kwok-Wing Tsui contributed equally to this study.

Abstract

Giant cell tumor (GCT) of bone is an aggressive non-cancerous tumor, which consists of multi-nucleated osteoclast-like giant cells, stromal cells, and monocytes. It is believed that stromal cells are the neoplastic component of this tumor. Expression of the receptor activator of nuclear factor kappa B ligand (RANKL) in the stromal cells stimulates the monocytes to form giant multi-nucleated osteoclast-like cells, causing bone over-resorption at the tumor site. Previously, our group has reported the up-regulation of RANKL in GCT of bone stromal cells, but the mechanism is unknown. Using stromal cell culture of GCT obtained from patients, we demonstrated the up-regulation of the transcriptional activator CCAAT/enhancer binding protein beta (C/EBPβ). RANKL promoter studies revealed that C/EBPβ over-expression induced RANKL promoter activity in a dose-dependent manner and a CCAAT-box within the region nt −357/−1 contributed to the basal transcription activity, with a possible C/EBPβ binding element in the region nt −460/−358 leading to further induction. Furthermore, we also showed that C/EBPβ bound to the RANKL promoter in GCT stromal cells in vivo by chromatin immunoprecipitation. To conclude, our study has shown that C/EBPβ is a RANKL promoter activator in stromal cells of GCT of bone and we have proposed a model in which C/EBPβ plays an important role in the osteolytic characteristics and pathological causes of GCT of bone. J. Cell. Biochem. 110: 438–446, 2010. © 2010 Wiley-Liss, Inc.

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