Vertical inhibition of the PI3K/Akt/mTOR pathway for the treatment of osteoarthritis

Authors

  • Dr. Jiezhong Chen,

    Corresponding author
    1. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia
    2. Illawarra Health and Medical Research Institute, University of Wollongong, Northfields Avenue, New South Wales 2522, Australia
    • Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia.
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  • Ross Crawford,

    1. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia
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  • Yin Xiao

    Corresponding author
    1. Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland 4059, Australia
    • Professor, Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Avenue, Kelvin Grove, Brisbane, QLD 4059, Australia.
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Abstract

Osteoarthritis is characterized by degenerative alterations of articular cartilage including both the degradation of extracellular matrix and the death of chondrocytes. The PI3K/Akt pathway has been demonstrated to involve in both processes. Inhibition of its downstream target NF-kB reduces the degradation of extracellular matrix via decreased production of matrix metalloproteinases while inhibition of mTOR increased autophagy to reduce chondrocyte death. However, mTOR feedback inhibits the activity of the PI3K/Akt pathway and inhibition of mTOR could result in increased activity of the PI3K/Akt/NF-kB pathway. We proposed that the use of dual inhibitors of PI3K and mTOR could be a promising approach to more efficiently inhibit the PI3K/Akt pathway than rapamycin or PI3K inhibitor alone and produce better treatment outcome. J. Cell. Biochem. 114: 245–249, 2013. © 2012 Wiley Periodicals, Inc.

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