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Genes2022; 13(12); 2210; doi: 10.3390/genes13122210

Short-Term Exposure to Ciprofloxacin Reduces Proteoglycan Loss in Tendon Explants.

Abstract: Fluoroquinolone antibiotics are associated with increased risk of tendinopathy and tendon rupture, which can occur well after cessation of treatment. We have previously reported that the fluoroquinolone ciprofloxacin (CPX) reduced proteoglycan synthesis in equine tendon explants. This study aimed to determine the effects of CPX on proteoglycan catabolism and whether any observed effects are reversible. Equine superficial digital flexor tendon explant cultures were treated for 4 days with 1, 10, 100 or 300 µg/mL CPX followed by 8 days without CPX. The loss of [S]-labelled proteoglycans and chemical pool of aggrecan and versican was studied as well as the gene expression levels of matrix-degrading enzymes responsible for proteoglycan catabolism. CPX suppressed [S]-labelled proteoglycan and total aggrecan loss from the explants, although not in a dose-dependent manner, which coincided with downregulation of RNA expression of MMP-9, -13, ADAMTS-4, -5. The suppressed loss of proteoglycans was reversed upon removal of the fluoroquinolone with concurrent recovery of MMP and ADAMTS RNA expression, and downregulated TIMP-2 and upregulated TIMP-1 expression. No changes in MMP-3 expression by CPX was observed at any stage. These findings suggest that CPX suppresses proteoglycan catabolism in tendon, and this is partially attributable to downregulation of matrix-degrading enzymes.
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Publication Date: 2022-11-25 PubMed ID: 36553476PubMed Central: PMC9777606DOI: 10.3390/genes13122210Google Scholar: Lookup
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  • Journal Article

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 study reveals that short-term exposure to the antibiotic ciprofloxacin (CPX) reduces the loss of proteoglycans in horse tendon tissues, an effect which is reversible after CPX removal. Proteoglycans are proteins significant for the structure and functioning of tendons.

Research Objective and Methodology

  • The research was designed to understand the effects of fluoroquinolone antibiotics, specifically ciprofloxacin, on proteoglycan synthesis and catabolism in tendon tissues. It aimed to reveal whether the effects observed are reversible after cessation of CPX treatment.
  • The study used equine, specifically horse, superficial digital flexor tendon tissues. These tissues were cultured and treated with varying concentrations of CPX for four days, followed by eight days without CPX.
  • The researchers tracked the loss of S-labelled proteoglycans and the chemical pool of aggrecan and versican, which are forms of proteoglycans. Furthermore, they studied the expression levels of matrix-degrading enzymes which are responsible for proteoglycan catabolism.

Main Findings

  • The researchers found that CPX treatment suppressed the loss of S-labelled proteoglycans and total aggrecan from the tissues, but this was not directly proportional to the dose of CPX.
  • There was a pronounced decline in RNA expression of certain matrix-degrading enzymes (MMP-9, -13, ADAMTS-4, -5), coinciding with the decreased proteoglycan loss.
  • Upon withdrawal of CPX, there was a reversal in proteoglycan loss and recovery of enzymes’ RNA expression. The researchers also observed downregulation of the enzyme TIMP-2 and upregulation of TIMP-1 in this process. However, CPX caused no fluctuations in MMP-3 expression at any stage.

Conclusions

  • The study suggests that CPX inhibits proteoglycan catabolism in tendon tissues, with the reduced loss of proteoglycans partially attributable to the downregulation of matrix-degrading enzymes.
  • The findings are significant as they may contribute towards understanding the effects of fluoroquinolone antibiotics on tendon health and the treatment of conditions like tendinopathy and tendon rupture.

Cite This Article

APA
James S, Daffy J, Cook J, Samiric T. (2022). Short-Term Exposure to Ciprofloxacin Reduces Proteoglycan Loss in Tendon Explants. Genes (Basel), 13(12), 2210. https://doi.org/10.3390/genes13122210

Publication

Genes
ISSN: 2073-4425
NlmUniqueID: 101551097
Country: Switzerland
Language: English
Volume: 13
Issue: 12
PII: 2210

Researcher Affiliations

James, Stuart
  • Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, VIC 3086, Australia.
Daffy, John
  • Department of Infectious Diseases, St Vincent's Hospital, Melbourne, VIC 3065, Australia.
Cook, Jill
  • Sports and Exercise Medicine Research Centre, La Trobe University, Melbourne, VIC 3086, Australia.
Samiric, Tom
  • Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Melbourne, VIC 3086, Australia.

MeSH Terms

  • Animals
  • Horses
  • Aggrecans / metabolism
  • Ciprofloxacin / pharmacology
  • Tendons / metabolism
  • Fluoroquinolones
  • Versicans / metabolism
  • RNA, Messenger / metabolism

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 2 times.
  1. Raleigh SM. Genetic and Epigenetic Factors That Predispose to Musculoskeletal Disorders. Genes (Basel) 2024 Sep 11;15(9).
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