Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis
Authors: Haythorn Abigail, Young Madeline, Stanton James, Zhang Jian, Mueller P.O.E., Halper Jaroslava
Summary
# Editorial Summary: Gene Expression in Equine Degenerative Suspensory Ligament Desmitis Degenerative suspensory ligament desmitis (DSLD) is a progressive systemic connective tissue disorder characterised by inappropriate proteoglycan accumulation in tendons and ligaments, leading to debilitating lameness; whilst first documented in Peruvian Paso horses, it affects multiple breeds and the underlying molecular drivers remain poorly understood. Using next-generation RNA sequencing of skin biopsies from six control and six affected Peruvian Pasos and Warmbloods, researchers identified differential expression of over 1500 genes, with notably elevated expression of bone morphogenetic protein 2 (BMP2), fibroblast growth factors (FGF5), connective tissue growth factor (CTGF), and multiple mediators of cell signalling, alongside increased hyaluronan synthesis genes—paradoxically coupled with decreased expression of many proteoglycan core proteins and collagen genes. The overexpression of BMP2 aligns with prior findings and implicates this transforming growth factor β family member in pathogenesis, whilst the unexpected downregulation of proteoglycan genes suggests either a currently unidentified proteoglycan variant or glycosyltransferase abnormality driving the pathological accumulation. For practitioners, these results indicate DSLD is fundamentally a systemic extracellular matrix disorder rather than a localised tissue pathology, supporting the need for whole-organism management strategies; the decreased immune gene expression confirms the non-inflammatory nature of affected tissues, whilst skin abnormalities and altered collagen metabolism suggest connective tissue dysfunction is indeed widespread and potentially detectable through non-invasive sampling.
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Practical Takeaways
- •DSLD is confirmed as a systemic connective tissue disorder affecting skin gene expression, supporting the hypothesis that clinical signs reflect widespread metabolic dysfunction rather than isolated ligament pathology
- •The disconnect between proteoglycan accumulation and decreased proteoglycan gene expression suggests an unidentified proteoglycan or glycosaminoglycan variant may be responsible for DSLD pathology, warranting further investigation before targeted therapies can be developed
- •Skin biopsies may serve as a non-invasive diagnostic tool to identify DSLD-affected horses through gene expression profiling, potentially enabling earlier intervention in breeding programs
Key Findings
- •Over 1500 genes showed differential expression in DSLD-affected horses compared to controls, with BMP2 overexpression confirmed via RNA sequencing
- •Growth factor genes (BMP2, FGF5, CTGF, EGF family members) and hyaluronan synthesis enzymes were upregulated while proteoglycan core proteins and most collagen genes were downregulated
- •Keratin gene overexpression and FGF5 upregulation correlate with reported skin abnormalities in DSLD horses
- •Decreased immune function gene expression aligns with the non-inflammatory nature of DSLD tissue pathology despite systemic proteoglycan accumulation