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 Degenerative suspensory ligament desmitis (DSLD) represents a systemic connective tissue disorder characterised by pathological proteoglycan accumulation in tendons and ligaments, causing lameness predominantly in Peruvian Pasos but also affecting other breeds; the underlying molecular drivers have remained poorly understood until now. Researchers employed next-generation sequencing on skin RNA from six control and six affected horses (four Peruvian Pasos and two Warmbloods) to identify differentially expressed genes, validating findings with rigorous bioinformatics algorithms accounting for false discovery rates. Over 1500 genes showed altered expression, including significant upregulation of growth factors (BMP2, FGF5, CTGF, EGF family members), signalling mediators (Fos, Myc, MAPK components), and keratins, alongside increased expression of two hyaluronan synthesis enzymes; conversely, most collagen genes, proteoglycan core proteins, and immune function genes were downregulated. The findings confirm previous suspicions regarding BMP2's central role whilst revealing systemic extracellular matrix dysfunction—the paradoxical decrease in proteoglycan gene expression despite tissue accumulation suggests either mutations in uncharacterised proteoglycans or altered glycosaminoglycan synthesis pathways warrant investigation. For practitioners, these results underscore DSLD as a metabolic disorder of connective tissue remodelling rather than inflammatory pathology, potentially opening targeted therapeutic avenues focused on growth factor regulation and matrix synthesis rather than conventional anti-inflammatory approaches.
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Practical Takeaways
- •DSLD is a systemic connective tissue disorder affecting multiple breeds; skin biopsies may serve as accessible diagnostic tool for detecting gene expression patterns
- •The dysregulation of growth factors (BMP2, FGF5) and abnormal extracellular matrix metabolism suggests targeted therapeutic interventions may be possible once specific pathogenic mechanisms are clarified
- •Lack of inflammatory gene expression indicates DSLD is non-inflammatory, which should inform management strategies focusing on biomechanical support rather than anti-inflammatory treatment alone
Key Findings
- •Over 1500 genes showed differential expression in DSLD-affected horses, including increased BMP2, FGF5, CTGF, and EGF family members
- •Two genes encoding hyaluronan synthesis enzymes were overexpressed while proteoglycan core protein genes were significantly decreased
- •Decreased collagen gene expression indicates abnormal connective tissue metabolism in DSLD
- •Keratin gene overexpression and FGF5 upregulation support documented skin abnormalities in DSLD horses