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Sorbitol-modified hyaluronic acid reduces oxidative stress, apoptosis and mediators of inflammation and catabolism in human osteoarthritic chondrocytes

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Abstract

Objective and design

Our study was designed to elucidate the precise molecular mechanisms by which sorbitol-modified hyaluronic acid (HA/sorbitol) exerts beneficial effects in osteoarthritis (OA).

Methods

Human OA chondrocytes were treated with increasing doses of HA/sorbitol ± anti-CD44 antibody or with sorbitol alone and thereafter with or without interleukin-1beta (IL-1β) or hydrogen peroxide (H2O2). Signal transduction pathways and parameters related to oxidative stress, apoptosis, inflammation, and catabolism were investigated.

Results

HA/sorbitol prevented IL-1β-induced oxidative stress, as measured by reactive oxygen species, p47-NADPH oxidase phosphorylation, 4-hydroxynonenal (HNE) production and HNE-metabolizing glutathione-S-transferase A4-4 expression. Moreover, HA/sorbitol stifled IL-1β-induced metalloproteinase-13, nitric oxide (NO) and prostaglandin E2 release as well as inducible NO synthase expression. Study of the apoptosis process revealed that this gel significantly attenuated cell death, caspase-3 activation and DNA fragmentation elicited by exposure to a cytotoxic H2O2 dose. Examination of signaling pathway components disclosed that HA/sorbitol prevented IL-1β-induced p38 mitogen-activated protein kinase and nuclear factor-kappa B activation, but not that of extracellular signal-regulated kinases 1 and 2. Interestingly, the antioxidant as well as the anti-inflammatory and anti-catabolic effects of HA/sorbitol were attributed to sorbitol and HA, respectively.

Conclusions

Altogether, our findings support a beneficial effect of HA/sorbitol in OA through the restoration of redox status and reduction of apoptosis, inflammation and catabolism involved in cartilage damage.

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Acknowledgments

This study was funded by Anteis S.A. (Geneva, Switzerland).

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Authors and Affiliations

  1. Orthopaedics Research Laboratory, Hôpital du Sacré-Cœur de Montréal, Room K-3045, 5400 Gouin Blvd. West, Montreal, QC, H4J 1C5, Canada

    John-Max Mongkhon, Maryane Thach, Qin Shi, Julio C. Fernandes & Mohamed Benderdour

  2. Department of Surgery, Université de Montréal, Montreal, QC, H4J 1C5, Canada

    Qin Shi, Julio C. Fernandes & Mohamed Benderdour

  3. Osteoarthritis Research Unit, Research Centre of the University of Montreal Hospital Center (CR-CHUM), Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, QC, H2L 4M1, Canada

    Hassan Fahmi

Authors
  1. John-Max Mongkhon
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  2. Maryane Thach
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  3. Qin Shi
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  4. Julio C. Fernandes
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  5. Hassan Fahmi
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  6. Mohamed Benderdour
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Correspondence to Mohamed Benderdour.

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Mongkhon, JM., Thach, M., Shi, Q. et al. Sorbitol-modified hyaluronic acid reduces oxidative stress, apoptosis and mediators of inflammation and catabolism in human osteoarthritic chondrocytes. Inflamm. Res. 63, 691–701 (2014). https://doi.org/10.1007/s00011-014-0742-4

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  • DOI: https://doi.org/10.1007/s00011-014-0742-4

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