Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts.
Authors: Luo Wei, Sandy John, Trella Katie, Gorski Daniel, Gao Shuguang, Li Jun, Brounts Sabrina, Galante Jorge, Plaas Anna
Journal: PloS one
Summary
Degenerative suspensory ligament desmitis (DSLD) causes progressive lameness in ageing Peruvian Pasos through collagen degradation and abnormal cartilage-like tissue formation in the ligament body, yet early detection remains elusive. Researchers analysed TGF-β signalling gene expression in adipose-derived stromal fibroblasts (ADSCs) from six affected and five unaffected horses, quantifying 76 target genes to identify a potential pre-breeding screening biomarker. Notably, 35 genes showed significantly reduced expression in DSLD-affected animals (p<0.05), with particularly marked downregulation of master metabolic regulators including ATF3, MAPK14, ALK1, SMAD6, FOS, CREBBP, NFKBIA and TGFBR2; critically, this expression deficit was largely reversed by exogenous TGF-β1 application, and blocked by TGF-β receptor inhibition, confirming the signalling pathway involved. The findings suggest DSLD reflects a systemic metabolic dysfunction rather than isolated ligament pathology, indicating that ADSCs from affected horses have impaired TGF-β responsiveness across multiple cellular processes. For practitioners, this work establishes a credible foundation for developing a blood-based diagnostic test to identify at-risk horses before breeding—potentially transforming prevention strategies in predisposed breeds—though translating these cell-level findings into a practical clinical assay will require further validation.
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Practical Takeaways
- •DSLD in Peruvian Paso horses involves a systemic TGF-β signaling deficiency in fibroblasts, not just local ligament pathology, suggesting potential for future pre-breeding genetic screening.
- •The altered expression of master metabolic regulators indicates DSLD may represent a systemic metabolic condition rather than purely mechanical ligament degeneration.
- •Understanding the TGF-β signaling pathway defect could eventually enable therapeutic targeting with TGF-β supplementation or related interventions.
Key Findings
- •35 of 76 TGF-β signaling target genes showed significantly lower expression (p<0.05) in adipose-derived stromal fibroblasts from DSLD-affected Peruvian Paso horses compared to unaffected horses.
- •Exogenous TGF-β1 administration largely eliminated the differential gene expression between DSLD-affected and unaffected cells.
- •The TGF-β signaling defect in DSLD involves master-regulator genes (ATF3, MAPK14, ACVRL1, SMAD6, FOS, CREBBP, NFKBIA, TGFBR2) indicating a generalized metabolic disturbance.
- •TGF-β1-mediated effects were blocked by TGF-βR1/2 inhibitor LY2109761, confirming signaling via TGF-βR1/2 complex.