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Downregulation of Notch Modulators, Tetraspanin 5 and 10, Inhibits Osteoclastogenesis in Vitro

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Abstract

Genetic studies in human and mice have pinpointed an essential role of Notch signaling in osteoblast and osteoclast differentiation during skeletal development and bone remodeling. However, the factors and pathways regulating Notch activation in bone cells remain largely unknown. In this in vitro study, we have provided evidence that two of the TspanC8 subfamily members of tetraspanins, Tspan-5 and Tspan-10, are up-regulated during osteoclast differentiation and knockdown of their expression by shRNAs dramatically inhibits osteoclastogenesis. Loss of Tspan-5 and Tspan-10 in osteoclast lineage cells results in attenuation of ADAM10 maturation and Notch activation. Therefore, these two tetraspanins play a critical role in osteoclast formation, at least in part, by modulating Notch signaling pathway.

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Acknowledgments

The authors would like to thank Drs. Stavros C Manolagas and Charles A Obrien for their critic of the manuscript prior to submission and Erin Hogan for her support in microscopic analysis. This work was supported by National Institutes of Health Grants AR062012 and P01 AG13918. This work was also supported by the University of Arkansas for Medical Sciences Tobacco Settlement Funds provided by the Arkansas Biosciences Institute.

Human and Animal Rights and Informed Consent

The usage and handling of mice were approved by UAMS Institutional Animal Care and Use Committee.

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Authors and Affiliations

  1. Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China

    Jian Zhou & Xiaolin Li

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences and the Central Arkansas Veterans Healthcare System, 4301 West Markham Street, Slot 587, Little Rock, AR, 72205, USA

    Jian Zhou, Toshifumi Fujiwara, Shiqiao Ye & Haibo Zhao

Authors
  1. Jian Zhou
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  2. Toshifumi Fujiwara
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  3. Shiqiao Ye
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  4. Xiaolin Li
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  5. Haibo Zhao
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Corresponding author

Correspondence to Haibo Zhao.

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Jian Zhou and Toshifumi Fujiwara authors have contributed equally to this study.

The authors have no conflict of interest.

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Zhou, J., Fujiwara, T., Ye, S. et al. Downregulation of Notch Modulators, Tetraspanin 5 and 10, Inhibits Osteoclastogenesis in Vitro. Calcif Tissue Int 95, 209–217 (2014). https://doi.org/10.1007/s00223-014-9883-2

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  • DOI: https://doi.org/10.1007/s00223-014-9883-2

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