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ATP promotes extracellular matrix biosynthesis of intervertebral disc cells

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Abstract

We have recently found a high accumulation of extracellular adenosine triphosphate (ATP) in the center of healthy porcine intervertebral discs (IVD). Since ATP is a powerful extracellular signaling molecule, extracellular ATP accumulation might regulate biological activities in the IVD. The objective of this study was therefore to investigate the effects of extracellular ATP on the extracellular matrix (ECM) biosynthesis of porcine IVD cells isolated from two distinct anatomical regions: the annulus fibrosus (AF) and nucleus pulposus (NP). ATP treatment significantly promotes ECM deposition and corresponding gene expression (aggrecan and type II collagen) by both cell types in three-dimensional agarose culture. A significant increase in ECM accumulation has been found in AF cells at a lower ATP treatment level (20 μM) compared with NP cells (100 μM), indicating that AF cells are more sensitive to extracellular ATP than NP cells. NP cells also exhibit higher ECM accumulation and intracellular ATP than AF cells under control and treatment conditions, suggesting that NP cells are intrinsically more metabolically active. Moreover, ATP treatment also augments the intracellular ATP level in NP and AF cells. Our findings suggest that extracellular ATP not only promotes ECM biosynthesis via a molecular pathway, but also increases energy supply to fuel that process.

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Acknowledgments

The authors thank Carlos Barrera and Brittany Rodriguez for their assistance with the isolation of the IVD cells.

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Authors and Affiliations

  1. Department of Biomedical Engineering, College of Engineering, University of Miami, P.O. Box 248294, Coral Gables, FL, 33124-0621, USA

    Silvia Gonzales, Chong Wang, Herman S. Cheung & Chun-Yuh Charles Huang

  2. Department of Neurological Surgery, University of Miami, Miami, FL, 33136, USA

    Howard Levene

  3. Geriatric Research, Education and Clinical Center, Miami Veterans Affairs Medical Center, Miami, FL, 33125, USA

    Herman S. Cheung

Authors
  1. Silvia Gonzales
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  2. Chong Wang
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  3. Howard Levene
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  4. Herman S. Cheung
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  5. Chun-Yuh Charles Huang
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Corresponding author

Correspondence to Chun-Yuh Charles Huang.

Additional information

This study was supported by grant AR056101 from the NIH and by a VA Merit Review Grant.

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Gonzales, S., Wang, C., Levene, H. et al. ATP promotes extracellular matrix biosynthesis of intervertebral disc cells. Cell Tissue Res 359, 635–642 (2015). https://doi.org/10.1007/s00441-014-2042-2

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  • DOI: https://doi.org/10.1007/s00441-014-2042-2

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