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Journal of Cellular Biochemistry

GPNMB enhances bone regeneration by promoting angiogenesis and osteogenesis: Potential role for tissue engineering bone

Authors

  • Xuefeng Hu,

    Corresponding author
    1. Department of Orthopedics, Chinese PLA 171 Hospital, Jiangxi, China
    • Correspondence to: Dr. Xuefeng Hu, Department of Orthopedics, Chinese PLA 171 Hospital, Jiangxi 332000, China.

      E-mail: xuefenghu11@163.com

      Correspondence to: Xin Xie, Institute of integrated medical information (IMI), Xi'an 710075, China; Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an 710069, China.

      E-mail: xiexin@nwu.edu.cn

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  • Ping Zhang,

    1. Institute of Integrated Medical Information (IMI), Xi'an, China
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  • Zhenjie Xu,

    1. Institute of Integrated Medical Information (IMI), Xi'an, China
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  • Hongdong Chen,

    1. Institute of Integrated Medical Information (IMI), Xi'an, China
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  • Xin Xie

    1. Institute of Integrated Medical Information (IMI), Xi'an, China
    2. Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xi'an, China
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  • The authors have no financial conflicts of interest.

ABSTRACT

Bone regeneration is a coordinated process involving the connection between blood vessels and bone cells. Glycoprotein non-metastatic melanoma protein B (GPNMB) is known to be vital in bone formation. However, the effect of GPNMB on bone regeneration and the underlying molecular mechanism are still undefined. Fibroblast growth factor receptor (FGFR)-mediating signaling is pivotal in bone formation and angiogenesis. Therefore, we assessed GPNMB function as a communicating molecule between osteoblasts and angiogenesis, and the possible correlation with FGFR-1 signaling. Recombinant GPNMB dose-dependently increased the differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts, as well as the mRNA levels of osteoblasts marker alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, these increases depended on the activation of FGFR-1 signaling, as pretreatment with FGFR-1 siRNA or its inhibitor SU5402 dramatically dampened GPNMB-induced osteogenesis. Additionally, GPNMB triggered dose-dependently the proliferation and migration of human umbilical vein endothelial cells (hUVECs), FGFR-1 phosphorylation, as well as capillary tube and vessels formation in vitro and in vivo. Blocking FGFR-1 signaling dampened GPNMB-induced angiogenic activity. Following construction of a rodent cranial defect model, scaffolds delivering GPNMB resulted in an evident increase in blood vessels and new bone formation; however, combined delivery of GPNMB and SU5402 abated these increase in defect sites. Taken together, these results suggest that GPNMB stimulates bone regeneration by inducing osteogenesis and angiogenesis via regulating FGFR-1 signaling. Consequently, our findings will clarify a new explanation about how GPNMB induces bone repair, and provide a potential target for bone regeneration therapeutics and bone engineering. J. Cell. Biochem. 114: 2729–2737, 2013. © 2013 Wiley Periodicals, Inc.

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