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

Veronique Saey,Siegrid De Baere,Koen Chiers,Richard Ducatelle,Siska Croubels,Stijn Schauvliege,Jonathan Tang,Gunther Van Loon

doi:10.1186/s12917-018-1454-8

Veronique Saey, Siegrid De Baere + Show 6 more

Open Access

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

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Abstract

BackgroundFriesian 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.ResultsMean 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).ConclusionsSince 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.

Highlights

Friesian horses are known for their high inbreeding rate resulting in several genetic diseases such as hydrocephaly and dwarfism
Considering the low PYD/DPD ratio of bone (3.8 in monkeys) [18] compared to soft tissues, and the mean PYD/DPD ratio of 9.6 in the Friesian horses in this study being very high compared to the result in Warmblood horses (5.8), it is likely that these cross-links originate from soft tissue catabolism
A similar elevation in the PYD/DPD ratio has been observed in human patients with scleroderma, a disease characterized by systemic excessive collagen deposition [19] and is attributed to increased collagen catabolism [20]

Summary

Introduction

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. In some of these, such as in dwarfism and hydrocephaly, the genetic background has been elucidated In both diseases, a mutation in a gene involved in protein glycosylation was detected. It has been suggested that this could be a manifestation of a presumed underlying soft tissue disorder [8]

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