Elevated urinary excretion of free pyridinoline in Friesian horses suggests a breed-specific increase in collagen degradation

doi:10.1186/s12917-018-1454-8

. 2018 Apr 25;14(1):139.

doi: 10.1186/s12917-018-1454-8.

Elevated urinary excretion of free pyridinoline in Friesian horses suggests a breed-specific increase in collagen degradation

Veronique Saey¹, Jonathan Tang², Richard Ducatelle³, Siska Croubels⁴, Siegrid De Baere⁴, Stijn Schauvliege⁵, Gunther van Loon⁶, Koen Chiers³

Affiliations

¹ Laboratory of Veterinary Pathology, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. veronique.saey@ugent.be.
² Bioanalytical Facility, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK.
³ Laboratory of Veterinary Pathology, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁴ Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁵ Deparment of Surgery and anaesthesiology of domestic animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁶ Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

PMID: 29699546
PMCID: PMC5921786
DOI: 10.1186/s12917-018-1454-8

Elevated urinary excretion of free pyridinoline in Friesian horses suggests a breed-specific increase in collagen degradation

Veronique Saey et al. BMC Vet Res. 2018.

. 2018 Apr 25;14(1):139.

doi: 10.1186/s12917-018-1454-8.

Authors

Veronique Saey¹, Jonathan Tang², Richard Ducatelle³, Siska Croubels⁴, Siegrid De Baere⁴, Stijn Schauvliege⁵, Gunther van Loon⁶, Koen Chiers³

Affiliations

¹ Laboratory of Veterinary Pathology, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium. veronique.saey@ugent.be.
² Bioanalytical Facility, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7UQ, UK.
³ Laboratory of Veterinary Pathology, Department of Pathology, Bacteriology and Avian Diseases, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁴ Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁵ Deparment of Surgery and anaesthesiology of domestic animals, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
⁶ Department of Large Animal Internal Medicine, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

PMID: 29699546
PMCID: PMC5921786
DOI: 10.1186/s12917-018-1454-8

Abstract

Background: Friesian horses are known for their high inbreeding rate resulting in several genetic diseases such as hydrocephaly and dwarfism. This last decade, several studies focused on two other presumed hereditary traits in Friesian horses: megaoesophagus and aortic rupture. The pathogenesis of these diseases remains obscure but an important role of collagen has been hypothesized. The purpose of this study was to examine possible breed-related differences in collagen catabolism. Urinary specimens from Friesian (n = 17, median age 10 years old) and Warmblood horses (n = 17, median age 10 years old) were assessed for mature collagen cross-links, i.e. pyridinoline (PYD) (=hydroxylysylpyridinoline/HP) and deoxypyridinoline (DPD) (lysylpyridinoline /LP). Solid-phase extraction was performed, followed by reversed-phase ion-paired liquid chromatography prior to tandem mass spectrometry (MS/MS) detection.

Results: Mean urinary concentrations of free PYD, expressed as fPYD/creatinine ratio, were significantly higher in Friesian horses compared to Warmblood horses (28.5 ± 5.2 versus 22.2 ± 9.6 nmol/mmol, p = 0.02) while mean fDPD/creatinine ratios were similar in both horse breeds (3.0 ± 0.7 versus 4.6 ± 3.7 nmol/mmol, p = 0.09).

Conclusions: Since DPD is considered a specific bone degradation marker and PYD is more widely distributed in connective tissues, the significant elevation in the mean PYD/DPD ratio in Friesian versus Warmblood horses (9.6 ± 1.6 versus 5.7 ± 1.8, p < 0.0001) suggests a soft tissue origin for the increased fPYD levels. Considering that a previous study found no differences in total collagen content between Friesian and Warmblood horses for tendon and aortic tissue, this indicates a higher rate of collagen degradation. The latter might, at least in part, explain the predisposition of Friesians to connective tissue disorders.

Keywords: Aortic rupture; Collagen; Cross-links; Horse; Mass spectrometry; Megaoesophagus.

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Conflict of interest statement

Ethics approval

An approved animal use protocol was waived by the chairperson of the ethical committee of the Faculty of Veterinary Medicine (Ghent University) as urine in the awake horses was collected by the owner/keeper not invasively during spontaneous voiding. The anesthetized horses were sampled by urinary catheterization as standard procedure during operation.

A written consent was obtained from the owner/keeper of each animal. All of the patients that were omitted to the University hospital, were treated following the institutional guidelines.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Friesian horses have a significantly higher mean urinary fPYD/creatinine concentration (28.5 ± 5.2 nmol/mmol) (, n = 17) in the urine compared to Warmblood horses (22.2 ± 9.6, n = 17) (p = 0.02)

**Fig. 2**
Mean urinary fDPD/creatinine concentrations in Friesian horses (3.0 ± 0.7 nmol/mmol, n = 17) showed no significant differences to the values in Warmblood horses (4.6 ± 3.7 nmol/mmol, n = 17) (p = 0.1)

**Fig. 3**
Mean fPYD/fDPD ratios in the urine from Friesian horses (9.6 ± 1.6, n = 17) were significantly higher compared to Warmblood horses (5.7 ± 1.8, n = 17) (p < 0.0001)

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References

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1. Seidler DG, Faiyaz-Ul-Hague M, Hansen U, Yip GW, Zaidi SH, Teebi AS, Kiesel L, Götte M. Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactaosyltransferase I (beta4GalT-7) J Mol Med (Berl) 2006;84(7):583–594. doi: 10.1007/s00109-006-0046-4. - DOI - PubMed
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[1] Gussekloo SWS, Lankester J, Kersten W, Back W. (2011) effect of differences in tendon properties on functionality of the passive stay apparatus in horses. AJVR. 2011;72(4):1–10. doi: 10.2460/ajvr.72.4.474. - DOI - PubMed

[2] Gussekloo SWS, Lankester J, Kersten W, Back W. (2011) effect of differences in tendon properties on functionality of the passive stay apparatus in horses. AJVR. 2011;72(4):1–10. doi: 10.2460/ajvr.72.4.474. - DOI - PubMed

[3] Leegwater PA, Vos-Loohuis M, Ducro BJ, Boegheim IJ, van Steenbeek FG, Nijman IJ, Monroe GR, Bastiaansen JWM, Dibbits BW, van de Goor LH, Hellinga I, Back W, Schurink A. Dwarfism with joint laxity in Friesian horses is associated with a splice mutation in B4GALT7. BMC Genomics. 2016; 10.1186/s12864-016-3186-0. - PMC - PubMed

[4] Leegwater PA, Vos-Loohuis M, Ducro BJ, Boegheim IJ, van Steenbeek FG, Nijman IJ, Monroe GR, Bastiaansen JWM, Dibbits BW, van de Goor LH, Hellinga I, Back W, Schurink A. Dwarfism with joint laxity in Friesian horses is associated with a splice mutation in B4GALT7. BMC Genomics. 2016; 10.1186/s12864-016-3186-0. - PMC - PubMed

[5] Seidler DG, Faiyaz-Ul-Hague M, Hansen U, Yip GW, Zaidi SH, Teebi AS, Kiesel L, Götte M. Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactaosyltransferase I (beta4GalT-7) J Mol Med (Berl) 2006;84(7):583–594. doi: 10.1007/s00109-006-0046-4. - DOI - PubMed

[6] Seidler DG, Faiyaz-Ul-Hague M, Hansen U, Yip GW, Zaidi SH, Teebi AS, Kiesel L, Götte M. Defective glycosylation of decorin and biglycan, altered collagen structure, and abnormal phenotype of the skin fibroblasts of an Ehlers-Danlos syndrome patient carrying the novel Arg270Cys substitution in galactaosyltransferase I (beta4GalT-7) J Mol Med (Berl) 2006;84(7):583–594. doi: 10.1007/s00109-006-0046-4. - DOI - PubMed

[7] Ducro BJ, Schurink A, Bastiaansen JW, Boegheim IJ, van Steenbeek FG, Vos-Loohuis M, Nijman IJ, Monroe GR, Hellinga I, Dibbits BW, Back W, Leegwater PA. A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC Genomics. 2015;16(1):761–768. doi: 10.1186/s12864-015-1936-z. - DOI - PMC - PubMed

[8] Ducro BJ, Schurink A, Bastiaansen JW, Boegheim IJ, van Steenbeek FG, Vos-Loohuis M, Nijman IJ, Monroe GR, Hellinga I, Dibbits BW, Back W, Leegwater PA. A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC Genomics. 2015;16(1):761–768. doi: 10.1186/s12864-015-1936-z. - DOI - PMC - PubMed

[9] Hedberg C, Oldfors A, Darin N. B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations. Eur J Hum Genet. 2014;22:707–710. doi: 10.1038/ejhg.2013.223. - DOI - PMC - PubMed

[10] Hedberg C, Oldfors A, Darin N. B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations. Eur J Hum Genet. 2014;22:707–710. doi: 10.1038/ejhg.2013.223. - DOI - PMC - PubMed

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