Gene expression analysis of subchondral bone, cartilage, and synovium in naturally occurring equine palmar/plantar osteochondral disease

Abstract

Osteoarthritis (OA) is a disease of the entire joint but the relationship between pathological events in various joint tissues is poorly understood. We examined concurrent changes in bone, cartilage, and synovium in a naturally occurring equine model of joint degeneration. Joints (n = 64) were grossly assessed for palmar/plantar osteochondral disease (POD) in racehorses that required euthanasia for unrelated reasons and assigned a grade of 0 (n = 34), 1 (n = 17), 2 or 3 (n = 13) using a recognized grading scheme. Synovium, cartilage, and subchondral bone were collected for histological and gene expression analysis. Relations between POD grade, cartilage histological score, and gene expression levels were examined using one-way analysis of variance or Kruskal-Wallis test and Spearman's correlation coefficient with corrections for multiple comparisons. Cartilage histological score increased in joints with POD grade 1 (p = 0.002) and 2 or 3 (p < 0.001) compared to 0. At grade 1, expression of COL1A1, COL2A1, and MMP1 increased and BGN decreased in subchondral bone while expression of BGN and ACAN decreased in cartilage. These changes further progressed at grades 2 and 3. POD grades 2 and 3 were associated with decreased expression of osteoclast inhibitor OPG and increased markers of cartilage degeneration (MMP13, COL1A1). Expression of the vascular endothelial growth factor decreased with POD grade and negatively correlated with cartilage histological score. Synovium showed no histological or transcriptomic changes related to pathology grade. Cartilage degeneration in POD is likely to be secondary to remodeling of the subchondral bone. Limited activation of proinflammatory and catabolic genes and moderate synovial pathology suggests distinct molecular phenotype of POD compared with OA.

Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study

“…47 Many canonical pathways enriched by the plasma and synovial fluid EV DE miRNA putative target genes were essential for or related to PTOA pathogenesis, including the "OA pathway" and "rheumatoid arthritis pathway." Additionally, downstream targets of these signaling pathways with known roles in OA pathogenesis were identified for plasma EVs consisting of matrix MMP3, 48 MMP14, 49 a disintegrin and MMP with thrombospondin motifs 2, 50 and receptor tyrosine-protein kinase (ERBB4). 51 Synovial fluid EV-signaling pathway downstream targets included VEGF, 50 histone deacetylase 4, 52 and specificity protein 1.…”

“…Additionally, downstream targets of these signaling pathways with known roles in OA pathogenesis were identified for plasma EVs consisting of matrix MMP3, 48 MMP14, 49 a disintegrin and MMP with thrombospondin motifs 2, 50 and receptor tyrosine-protein kinase (ERBB4). 51 Synovial fluid EV-signaling pathway downstream targets included VEGF, 50 histone deacetylase 4, 52 and specificity protein 1. 53 In our study, fibrosis was the most significant canonical pathway identified from both plasma and synovial fluid EV DE miRNAs and their putative mRNAs targets.…”