title: Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts.
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.
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America.|Department of Biochemistry, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Sandy
authors.affiliation: Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, United States of America.
authors.forename: Katie
authors.initials: K
authors.lastname: Trella
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gorski
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Surgical Sciences, University of Wisconsin-Madison, School of Veterinary Medicine, Madison, Wisconsin, United States of America.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Brounts
authors.affiliation: Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Galante
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL, United States of America.|Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, United States of America.
authors.forename: Anna
authors.initials: A
authors.lastname: Plaas
mesh_terms: D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006734:Horse Diseases / Q000473:pathology*; D006736:Horses; D008022:Ligaments; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D011720:Pyrazoles / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D002843:Chromatin; C530108:LY2109761; D011720:Pyrazoles; D011758:Pyrroles; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II