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U0126 promotes osteogenesis of rat bone-marrow-derived mesenchymal stem cells by activating BMP/Smad signaling pathway

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Abstract

U0126 has been reported as a specific inhibitor of the ERK1/2 signaling pathway, which plays a vital role during the osteogenic differentiation of mesenchymal stem cells (MSCs). We report the positive effect of U0126 on the osteogenesis of rat MSCs. We find that U0126 promotes the osteogenic differentiation of rat MSCs as demonstrated by the quantitative real-time polymerase chain reaction for osteogenic markers, alkaline phosphatase activity and calcium nodule formation. Our data indicate that U0126 enhances the BMP/Smad signaling pathway in rat MSCs, while inhibiting the ERK1/2 signaling pathway. Furthermore, Western blot results demonstrate that U0126 increases Smad1/5/8 phosphorylation synergistically with β-glycerophosphate. In addition, U0126 significantly increases the expression of BMP2 during the process of osteogenesis in rat MSCs and the level of phosphorylated Smad1/5/8 is significantly reduced by BMP2 antibody, suggesting that U0126 also promotes the expression of BMP2 to enhance Smad proteins phosphorylation. Thus, we demonstrate a novel function for U0126 in promoting osteogenic differentiation of rat MSCs by the activation of the BMP/Smad signaling pathway.

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Authors and Affiliations

  1. Department of Orthopaedics & Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

    Liangliang Xu, Yang Liu, Kuixing Wang, Yinmei Wong, Sien Lin & Gang Li

  2. School of Biomedical Sciences, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China

    Yonghui Hou

  3. MOE Key Laboratory of Regenerative Medicine, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, People’s Republic of China

    Gang Li

  4. The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, People’s Republic of China

    Gang Li

  5. Li Ka Shing Institute of Health Institute, Prince of Wales Hospital, The Chinese University of Hong Kong, Room 904, 9/F, Shatin, Hong Kong, SAR, People’s Republic of China

    Gang Li

Authors
  1. Liangliang Xu
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  2. Yang Liu
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  3. Yonghui Hou
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  4. Kuixing Wang
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  5. Yinmei Wong
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  6. Sien Lin
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  7. Gang Li
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Corresponding author

Correspondence to Gang Li.

Additional information

Liangliang Xu, Yang Liu and Yonghui Hou contributed equally to this work.

The authors are grateful for financial support from the Hong Kong Government Research Grant Council, General Research Fund (CUHK471110 and CUHK470813) to G.L. This study was also supported in part by the SMART program, the Lui Che Woo Institute of Innovative Medicine, Faculty of Medicine, The Chinese University of Hong Kong and a donation from the Lui Che Woo Foundation, Hong Kong.

The authors declare that they have no competing or conflicting interests.

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Xu, L., Liu, Y., Hou, Y. et al. U0126 promotes osteogenesis of rat bone-marrow-derived mesenchymal stem cells by activating BMP/Smad signaling pathway. Cell Tissue Res 359, 537–545 (2015). https://doi.org/10.1007/s00441-014-2025-3

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  • DOI: https://doi.org/10.1007/s00441-014-2025-3

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