Louise Bundgaard

Osteoarthritis (OA) is a chronic and progressive joint disease that can cause permanent loss of joint function. OA is highly prevalent in horses, dogs, and cats, affecting different joints and leading to reduced mobility and chronic pain. Different risk factors for animal OA have been identified, including trauma and breed. Inflammation is a hallmark of the disease, with various underlying mechanisms such as cyclooxygenase and metalloproteinase activation, nerve growth factor, cytokine, and prostaglandin E ₂ upregulation, among others. Although disease complexity makes OA difficult to treat, enormous advances have been made in regard to therapeutic options, especially due to the identification and better understanding of the common mechanisms underlying human and animal disease. Indeed, to date, numerous therapies have been developed over the years and are available to treat animal OA, including COX inhibitors, PGE₂ 4 receptor blockers, chondroprotective agents, biologicals, and medical devices for veterinary medicine, as well as those used to treat human disease. Herein, the different therapies available for animal OA, treatment regimens for each species, mechanisms of action, benefits, setbacks, and challenges for achieving a better quality of life and longevity for veterinary patients are presented and discussed.

In human proteomics, substantial efforts are ongoing to leverage large collections of mass spectrometry (MS) fragment ion spectra into extensive spectral libraries (SL) as a resource for data independent acquisition (DIA) analysis. Currently, such initiatives in equine research are still missing. Here we present a large-scale equine SL, comprising 6394 canonical proteins and 89,329 unique peptides, based on data dependent acquisition analysis of 75 tissue and body fluid samples from horses. The SL enabled large-scale DIA-MS based quantification of the same samples to generate a quantitative equine protein distribution atlas to infer dominant proteins in different organs and body fluids. Data mining revealed 163 proteins uniquely identified in a specific type of tissue or body fluid, serving as a starting point to determine tissue-specific or tissue-type-specific proteins. We showcase the SL by highlighting proteome dynamics in equine synovial fluid samples during experimental lipopolysaccharide-induced arthritis. A fuzzy c-means cluster analysis pinpointed SERPINB1, ATRN, NGAL, LTF, MMP1, and LBP as putative biomarkers for joint inflammation. This SL provides an extendable resource for future equine studies employing DIA-MS.

Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. Chondrocyte signalling was analysed using luciferase-based transcription factor activity assays. EV protein cargo appears to be more important during osteoarthritis progression than small non-coding RNAs. Cluster analysis revealed plasma-EVs represented a time-dependent response to osteoarthritis induction associated with supramolecular complexes. Clusters for synovial fluid-derived EVs were associated with initial osteoarthritis response and represented immune/inflammatory pathways. Factor analysis for plasma-derived EVs correlated with day post-induction and were primarily composed of proteins modulating lipid metabolism. Synovial fluid-derived EVs factors represented intermediate filament and supramolecular complexes reflecting tissue repair. There was a significant interaction between time and osteoarthritis for CRE, NFkB, SRE, SRF with a trend for osteoarthritis synovial fluid-derived EVs at later time points to have a more pronounced effect.

The authors have withdrawn their manuscript whilst they perform additional analyses to test some of their conclusions further. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author ( uadk@dtu.dk ).

This study addresses the presence and location of natural pigmentation, potentially pathological changes in pigment, interruptions of the natural lining (scars), roughness, and erosions/contusion (bruising) in and around the corners of the lips of 206 horses presented to a veterinarian for routine preventative dental treatment. After sedation, photographs were taken and later evaluated for the presence of lesions. During the photographic analysis, the Oral Commissure Assessment (OCA) protocol was developed to map precisely the areas of skin and mucosa around the corners of the lips, and the presence of lesions was recorded for each area. Potentially pathological pigment changes occurred more frequently in horses with a higher level of training (p = 0.04) and in light-coloured horses (p = 0.0004), but there was no association with the current use of a bit or the discipline that the horse participated in (p = 0.20). Scars occurred more frequently in horses competing at a higher level. Only two horses had contusions or erosions, five had ulcers, and none showed bleeding; these numbers were too low for statistical analysis. Using the OCA protocol provides a detailed method for categorizing and recording lesions in and around the corners of the lips, including natural vs. potential and/or definite pathological character.

This study addresses the presence and location of oral lesions in 342 dressage, show jumping, and eventing horses examined at an obligatory veterinary inspection before competing in the Danish National Championship in 2020. Ulcers in the lip commissures were photographed for subsequent pathological analysis. If a lesion was found at the lip commissures on one side, there was an increased risk of finding a similar lesion on the other side (ulcer: p < 0.0001; scarring/depigmentation: p < 0.0001; fissure: p = 0.002; erosion/contusion: p < 0.0001). At the lip commissures, external (cutaneous) ulcers were correlated with internal (mucosal) ulcers (p < 0.0001) and with scarring/depigmentation (p < 0.0001). Both mucosal and cutaneous ulcers were correlated with scarring/depigmentation (p < 0.0001). Erosion/contusion at the lip commissures was associated with similar lesions on the bars (p = 0.0002), and ulcers of the buccal mucosa were associated with ulcers on the bars (p = 0.003). Dental hooks or sharp enamel points on one side were associated with similar lesions on the other side (p < 0.0001). Dental findings were not related to mucosal ulcers or erosion/contusion at the lip commissures but were associated with scarring/depigmentation (p = 0.01).