Sonic hedgehog enhances the proliferation and osteogenic differentiation of bone marrow-derived mesenchymal stem cells

Authors

  • Jia-Qin Cai,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
    2. West China School of Pharmacy, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Yi-Zhou Huang,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Xiao-He Chen,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Hong-Lei Xie,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Hong-Ming Zhu,

    Corresponding author
    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Li Tang,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
    2. West China School of Pharmacy, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Zhi-Ming Yang,

    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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  • Yong-Can Huang,

    Corresponding author
    1. Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR 999077, Peoples Republic of China
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  • Li Deng

    Corresponding author
    1. Division of Stem Cell and Tissue Engineering, Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, Peoples Republic of China
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Present address: Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, People's Republic of China

Correspondence may be addressed to either of these authors (email y.c.huang@hku.hk or dengli2000@gmail.com).

Abstract

MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration because of their self-renewal and multi-differentiation potential. Shh (sonic hedgehog) is involved in the skeletal formation during embryo development and skeletal regeneration. However, how Shh regulates the biological characteristics of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony-forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N increased the ratio of cells in S and G2/M phase, as well as the number of Ki-67+ cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml) up-regulated the expression of genes encoding Cbfa-1 (core-binding factor α1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information reveals some potential of rShh-N in the therapeutics of bone-related diseases.

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