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Veterinary surgery : VS2022; 52(1); 146-156; doi: 10.1111/vsu.13898

Clodronate disodium is neither cytotoxic nor cytoprotective to normal and recombinant equine interleukin-1β-treated joint tissues in vitro.

Abstract: To determine the effects of clodronate disodium (CLO) on control and recombinant equine interleukin-1β (IL-1β)-treated equine joint tissues. Methods: In vitro experimental study. Methods: Cartilage explants, chondrocytes, and synoviocytes (n = 3 horses). Methods: Monolayer cultures of chondrocytes and synoviocytes from three horses were subjected to: control media (CON), 5 ng/ml CLO (C/low), 50 ng/ml CLO (C/med), 100 ng/ml CLO (C/high), with and without IL-1β, and 10 ng/ml IL-1β (IL) alone for 72 hours. Cartilage explants from three horses were subjected to CON, IL, C/low, and C/med with and without IL-1β for 72 hours. Culture media was analyzed for prostaglandin-E2 (PGE2 ), interleukin-6 (IL-6), and nitric oxide (NO). Explant media was analyzed for glycosaminoglycan (GAG) content and NO. At 72 hours, explant and monolayer culture viability were assessed, and explant GAG content was measured. Results: IL-1β treatment resulted in higher media concentrations of GAG, NO, PGE2 , and IL-6 compared to the CON treatment (p < .05), demonstrating a catabolic effect of IL-1β on explants and monolayer cultures. CLO treatments did not increase media concentrations of GAG, NO, PGE2 , or IL-6 compared to CON, indicating no cytotoxic effect. Nevertheless, CLO treatments administered to IL-1β-treated monolayer cultures and explants did not significantly reduce the inflammatory response regardless of concentration. Conclusions: CLO did not demonstrate cytotoxic nor cytoprotective effects in normal and IL-1β-stimulated chondrocytes, synoviocytes or explants in culture. Conclusions: This study does not support the use of CLO as an anti-inflammatory treatment. Further research is necessary to confirm any anti-inflammatory effects of CLO on joint tissues.
© 2022 American College of Veterinary Surgeons.
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Publication Date: 2022-10-10 PubMed ID: 36217704DOI: 10.1111/vsu.13898Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research paper investigates the impact of clodronate disodium (CLO) on both normal and interleukin-1β (IL-1β)-treated equine joint tissues, concluding that the substance neither harms nor protects the tissues and thus should not be used as an anti-inflammatory treatment.

Research Methods

  • The researchers undertook an in vitro experimental study involving monolayer cultures of chondrocytes and synoviocytes (the cellular components of cartilage and the synovial membrane in joints respectively) derived from three horses.
  • These tissues were subjected to various conditions: a control environment, CLO concentrations at three different levels, with and without IL-1β present, and IL-1β alone, for a duration of 72 hours.
  • Additionally, cartilage explants (pieces of tissue extracted to be studied in a different environment) from the same horses were exposed to similar conditions.
  • The researchers then analyzed the culture media (the substance in which the cells were grown) for concentrations of prostaglandin-E (PGE), interleukin-6 (IL-6), and nitric oxide (NO), which are all markers of inflammation and cell damage.
  • For the explant media, they also counted the amount of glycosaminoglycan (GAG), a compound that forms a vital component of the joint’s cartilage.

Research Findings

  • It was found that IL-1β treatment led to greater media concentrations of GAG, NO, PGE, and IL-6 than in controls, indicating that IL-1β has a destructive effect on explants and monolayer cultures.
  • In contrast, CLO treatments did not increase the media amounts of these compounds, suggesting no harmful effect from CLO.
  • However, administering CLO to IL-1β-treated cultures and explants did not significantly reduce the inflammatory response, regardless of the CLO concentration. These findings demonstrate that CLO lacks a protective effect on these cultures and explants.

Conclusions

  • The study concludes that clodronate disodium does not demonstrate either cytotoxic (harmful to cells) or cytoprotective (protective of cells) effects in both normal and IL-1β-stimulated chondrocytes, synoviocytes, or explants in culture.
  • Subsequently, they do not support the use of CLO as an anti-inflammatory treatment. They suggest further research to confirm any potential anti-inflammatory effects of CLO on joint tissues.

Cite This Article

APA
Vergara-Hernandez FB, Panek CL, Nielsen BD, Robison CI, Colbath AC. (2022). Clodronate disodium is neither cytotoxic nor cytoprotective to normal and recombinant equine interleukin-1β-treated joint tissues in vitro. Vet Surg, 52(1), 146-156. https://doi.org/10.1111/vsu.13898

Publication

Veterinary surgery : VS
ISSN: 1532-950X
NlmUniqueID: 8113214
Country: United States
Language: English
Volume: 52
Issue: 1
Pages: 146-156

Researcher Affiliations

Vergara-Hernandez, Fernando B
  • Department of Animal Science, College of Agricultural and Natural Resources, Michigan State University, East Lansing, Michigan, USA.
Panek, Char L
  • Department of Large Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Nielsen, Brian D
  • Department of Animal Science, College of Agricultural and Natural Resources, Michigan State University, East Lansing, Michigan, USA.
Robison, Cara I
  • Department of Animal Science, College of Agricultural and Natural Resources, Michigan State University, East Lansing, Michigan, USA.
Colbath, Aimee C
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.

MeSH Terms

  • Animals
  • Horses
  • Interleukin-1beta / pharmacology
  • Interleukin-1beta / metabolism
  • Clodronic Acid / pharmacology
  • Clodronic Acid / metabolism
  • Cartilage, Articular
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Chondrocytes
  • Glycosaminoglycans / pharmacology
  • Glycosaminoglycans / metabolism
  • Antineoplastic Agents / pharmacology

Grant Funding

  • American College of Veterinary Surgeons Foundation

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Citations

This article has been cited 1 times.
  1. Vergara-Hernandez FB, Nielsen BD, Popovich JM Jr, Panek CL, Logan AA, Robison CI, Ehrhardt RA, Johnson TN, Chargo NJ, Welsh TH Jr, Bradbery AN, Leatherwood JL, Colbath AC. Clodronate disodium does not produce measurable effects on bone metabolism in an exercising, juvenile, large animal model. PLoS One 2024;19(4):e0300360.
    doi: 10.1371/journal.pone.0300360pubmed: 38626145google scholar: lookup
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