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The role of mitochondrial reactive oxygen species in cartilage matrix destruction

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Abstract

Upregulation of matrix metalloproteinases (MMPs) is a hallmark of osteoarthritis progression; along with the role reactive oxygen species (ROS) may play in this process. Moreover, mitochondrial DNA damage and dysfunction are also present in osteoarthritic chondrocytes. However, there are no studies published investigating the direct relationship between mitochondrial ROS, mitochondrial DNA damage, and MMP expression. Therefore, the purpose of the present study was to evaluate whether mitochondrial DNA damage and mitochondrial-originated oxidative stress modulates matrix destruction through the upregulation of MMP protein levels. MitoSox red was utilized to observe mitochondrial ROS production while a Quantitative Southern blot technique was conducted to analyze mitochondrial DNA damage. Additionally, Western blot analysis was used to determine MMP protein levels. The results of the present study show that menadione augmented mitochondrial-generated ROS and increased mitochondrial DNA damage. This increase in mitochondrial-generated ROS led to an increase in MMP levels. When a mitochondrial ROS scavenger was added, there was a subsequent reduction in MMP levels. These studies reveal that mitochondrial integrity is essential for maintaining the cartilage matrix by altering MMP levels. This provides new and important insights into the role of mitochondria in chondrocyte function and its potential importance in therapeutic approaches.

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Authors and Affiliations

  1. Department of Cell Biology and Neuroscience, University of South Alabama, 307 University Boulevard N., MSB 1201, Mobile, AL, 36688-0002, USA

    Kendra N. Reed & Glenn Wilson

  2. Department of Orthopaedic Surgery, University of South Alabama, 3421 Medical Park Dr., Mobile, AL, 36693, USA

    Albert Pearsall

  3. Department of Cell Biology and Neuroscience and Department of Orthopaedic Surgery, University of South Alabama, 307 University Boulevard N., MSB 1201, Mobile, AL, 36688-0002, USA

    Valentina I. Grishko

Authors
  1. Kendra N. Reed
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  2. Glenn Wilson
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  3. Albert Pearsall
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  4. Valentina I. Grishko
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Correspondence to Glenn Wilson.

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Reed, K.N., Wilson, G., Pearsall, A. et al. The role of mitochondrial reactive oxygen species in cartilage matrix destruction. Mol Cell Biochem 397, 195–201 (2014). https://doi.org/10.1007/s11010-014-2187-z

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  • DOI: https://doi.org/10.1007/s11010-014-2187-z

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