Transcriptomic profile of peripheral whole blood reveals novel potential diagnostic gene biomarkers of degenerative joint disease (osteoarthritis) in German shepherd dogs

Abstract

Degenerative joint disease (osteoarthritis) is one of the most common chronic musculoskeletal diseases in human population. Susceptibility to osteoarthritis has been associated with more than 90 quantitative trait loci (QTL). Canine forms of degenerative joint disease are very similar to those in humans and represent a welfare problem in the dog world population. In this study, we Investigated the transcriptomic profile of peripheral whole blood in German shepherd dogs with degenerative joint disease to identify biomarkers. The bulk RNA-seq experiment was performed in a cohort of 12 adult dogs, 5 affected and 7 unaffected. Radiographs in affected dogs revealed severe osteoarthritis in hip and elbow joints. The differential expression analysis showed 688 genes differentially expressed in comparison to the control group (P-value <0.05). This pool of genes was functional annotated for signaling pathways using PANTHER tools. The enriched genes were those associated with inflammation mediate by chemokine and cytokine signaling pathway. To gain further insights of the functional role of these genes in osteoarthritis, we selected those with foldchange values less or equal to −2.0 and bigger or equal to 2.0. We found 8 genes highly upregulated and 9 genes strongly downregulated. Prioritization of these genes according to their functional knowledge revealed 2 clear top candidate biomarkers. The downregulated OSCAR gene encodes the osteoclast associated protein which is involved in the regulation ofosteoclastogenesis and bone homeostasis. On the other hand, the upregulated TRPM2 gene is involved in oxidative stress-induced cell death and inflammation processes. Our data suggests OSCAR and TRPM2 as novel candidate biomarkers for degenerative joint disease in German shepherds, this may facilitate genetic testing to improve the diagnosis and clinical treatment.