Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts.

Wei Luo,Shuguang Gao,Sabrina Brounts,John Sandy,Jorge Galante,Daniel Gorski,Jun Li,Katie Trella,Anna Plaas

doi:10.1371/journal.pone.0167069

Abstract

Equine degenerative suspensory ligament desmitis (DSLD) in Peruvian Paso horses typically presents at 7–15 years and is characterized by lameness, focal disorganization of collagen fibrils, and chondroid deposition in the body of the ligament. With the aim of developing a test for disease risk (that can be used to screen horses before breeding) we have quantified the expression of 76 TGFβ-signaling target genes in adipose-derived stromal fibroblasts (ADSCs) from six DSLD-affected and five unaffected Paso horses. Remarkably, 35 of the genes showed lower expression (p<0.05) in cells from DSLD-affected animals and this differential was largely eliminated by addition of exogenous TGFβ1. Moreover, TGFβ1-mediated effects on expression were prevented by the TGFβR1/2 inhibitor LY2109761, showing that the signaling was via a TGFβR1/2 complex. The genes affected by the pathology indicate that it is associated with a generalized metabolic disturbance, since some of those most markedly altered in DSLD cells (ATF3, MAPK14, ACVRL1 (ALK1), SMAD6, FOS, CREBBP, NFKBIA, and TGFBR2) represent master-regulators in a wide range of cellular metabolic responses.

Highlights

Degenerative suspensory ligament desmitis (DSLD) is prevalent in specific horse breeds, such as the Peruvian Paso, Paso Fino, American Saddlebred, Quarter Horse, and Akhal-Teke [1, 2] and is rare in pony and draft breeds amongst others
The data indicated that the expression of FN1, TGFβ1, COL3A1, COL5A1, COL5A2, and ACAN was similar in Non-Pasos and DSLDs but higher (p
The statistically higher values for the NA-Paso group were largely due to the data for one horse (# 5, “S1 Table”), except for TGFβ1 where the higher values were in horse #4, so that when the group comparisons were made between animals (Non-Pasos (N = 4), DSLDs (N = 14) and NA-Pasos (N = 2), the differences did not reach statistical significance

Summary

Introduction

Degenerative suspensory ligament desmitis (DSLD) is prevalent in specific horse breeds, such as the Peruvian Paso, Paso Fino, American Saddlebred, Quarter Horse, and Akhal-Teke [1, 2] and is rare in pony and draft breeds amongst others. The horses present with only the suspensory ligament affected, and no detectable gross changes in flexor tendons or even extensor tendons have been reported. It has been suggested that DSLD may be a systemic disorder involving all tissues and organs [1], but with a more significant connective tissue component. This may emerge more distinctly, due to the more extensive mechanical stressors on the affected SLs

Methods

Results

Conclusion