Effect of clodronate on gene expression in the peripheral blood of horses - PubMed (original) (raw)

Effect of clodronate on gene expression in the peripheral blood of horses

Callie V Wilcox et al. J Vet Pharmacol Ther. 2024 May.

Abstract

There are two FDA-approved bisphosphonate products, clodronate (Osphos®) and tiludronate (Tildren®), for use in horses. It is hypothesized that bisphosphonates can produce analgesic effects and prevent proper healing of microcracks in bone. Therefore, bisphosphonate use is banned in racehorses. However, bisphosphonates have a short detection window in the blood before sequestration in the skeleton, making the reliability of current drug tests questionable. Seven exercising Thoroughbred horses were administered clodronate (1.8 mg/kg i.m.), and four were administered saline. RNA was isolated from peripheral blood mononuclear cells (PBMCs) collected immediately before a single dose of clodronate or saline and then on Days 1, 6, 28, 56 and 182 post-dose. mRNA was sequenced and analysed for differentially expressed transcripts. While no single transcripts were differentially expressed, pathway analysis revealed that p38 MAPK (p = .04) and Ras (p = .04) pathways were upregulated, and cadherin signalling (p = .02) was downregulated on Day 1. Previously investigated biomarkers, cathepsin K (CTSK) and type 5 acid phosphatase (ACP5), were analysed with RT-qPCR in a targeted gene approach, with no significant difference observed. A significant effect of time on gene expression for ACP5 (p = .03) and CTSK (p < .0001) was observed. Thus, these genes warrant further investigation for detecting clodronate use over time.

Keywords: bisphosphonate; blood; bone; clodronate; gene; horse.

© 2024 The Authors. Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

Figures

FIGURE 1

FIGURE 1

Timeline outlining blood collection time points for PBMC RNA isolation.

FIGURE 2

FIGURE 2

Fold change of (a) ACP5 and (b) CTSK mRNA as determined by qPCR at each time point. Expression is in relation to B2M. There is a significant effect of time on gene expression for both ACP5 (p = .03) and CTSK (p < .0001). *p < .05, ****p < .0001.

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