A pilot study of microRNA assessment as a means to identify novel biomarkers of spontaneous osteoarthritis in dogs
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE212544 | GEO | 2022/09/04
REPOSITORIES: GEO
Similar Datasets
Project description:A pilot study of microRNA assessment as a means to identify novel biomarkers of spontaneous osteoarthritis in dogs
| PRJNA875931 | ENA
Project description:Objective: The objective of this study was to characterize extracellular vesicles (EVs) in plasma and synovial fluid obtained from horses with and without naturally occurring post-traumatic osteoarthritis (PTOA). Animals (Samples): EVs were isolated from plasma and synovial fluid from horses with (n = 6) and without (n = 6) PTOA. Methods: Plasma and synovial fluid EVs were characterized with respect to quantity, size, and surface markers. Small RNA sequencing was performed and differentially expressed miRNAs underwent bioinformatic analysis to identify putative targets and to explore potential associations with specific biological processes. Results: Plasma and synovial fluid samples from horses with PTOA had a significantly higher proportion of exosomes and a lower proportion of microvesicles compared to horses without PTOA. Small RNA sequencing revealed several differentially expressed miRNAs including miR-144, miR-219-3p, and miR-199a-3p in plasma and miR-199a-3p, miR-214, and miR-9094 in synovial fluid EVs. Bioinformatics analysis of the differentially expressed miRNAs highlighted their potential role in fibrosis, differentiation of chondrocytes, apoptosis, and inflammation pathways in PTOA. Clinical Relevance: We have identified dynamic molecular changes in small non-coding signatures of plasma and synovial fluid EVs in horses with naturally occurring PTOA. These findings could serve to identify promising biomarkers in the pathogenesis of PTOA, to facilitate the development of targeted therapies, and to aid in establishing appropriate translational models of PTOA.
2024-06-01 | GSE256340 | GEO
Project description:Identify differentially expressed microRNAs in mild and severe equine distal interphalangeal joint osteoarthritis plasma and synovial fluid samples Determine the effects of selected osteoarthritis-related miRNAs on equine chondrocytes in monolayer culture through the application of miRNA agomirs and antagomirs
2023-01-30 | GSE205409 | GEO
Project description:Background: Pain from coxofemoral joint (CFJ) osteoarthritis (OA) characteristic of canine hip dysplasia (CHD) afflicts many dogs. Intervertebral disc (IVD) degeneration is a common CFJ OA comorbidity. Non-steroidal anti-inflammatory drug (NSAID) administration is standard for treatment of pain from degenerative joint disease. Potential side effects and tolerance from prolonged administration drive efforts to identify compounds that may be alternatives to or combined with NSAIDs. Agmatine, decarboxylated arginine, reportedly alleviates neuropathic pain, a likely component of OA pain. The objective of this study was to compare treatment response to agmatine and carprofen in dogs with varying degrees of CFJ OA with or without IVD degeneration and to test the hypothesis that agmatine improves hindlimb use comparably to carprofen and more than placebo. Methods: Nine hound-type dogs received oral carprofen (4.4 mg/kg, sid) for 7 days. Six months later, oral agmatine sulfate (25 mg/kg, bid) or placebo (hydroxypropyl methylcellulose, bid) was administered to the same dogs for 28 days with a 2 week washout period between treatments. Validated pain assessment scores were measured before treatment and every seven days throughout the treatment periods. Serum chemistry levels and ground reaction forces (GRF) were quantified before and after each treatment period. A board-certified radiologist quantified radiographic CFJ OA based on Orthopedic Foundation for Animals criteria and IVD degeneration on magnetic resonance images. GRFs were compared among treatments at each time point and among time points for each treatment. Results: There were no detectable adverse effects with any treatment. Significant results included improved GRFs in dogs with mild CFJ OA (N = 3) following agmatine administration compared to carprofen or placebo and a trend for improved GRFs in dogs with moderate CFJ OA (N = 2) following carprofen vs. agmatine or placebo. Neither agmatine nor carprofen improved GRFs in dogs with severe CFJ OA (N = 4). The GRFs improved in dogs with IVD degeneration (N = 3) following carprofen treatment compared to agmatine or placebo regardless of CFJ OA score, but no effect was observed in dogs with normal lumbar spines (N = 6). Conclusions: Results support agmatine over carprofen treatment to improve limb use in dogs with early or mild CFJ OA, while carprofen may be the better choice for dogs with moderate CFJ OA or IVD degeneration regardless of CFJ OA severity.
| S-EPMC6315183 | biostudies-literature
Project description:Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA. The genes upregulated during OA can be used to identify disease characteristic genes. 10 microarrays of end-stage OA synovial biopsies were compared to 7 microarrays of synovial biopsies from individuals without a joint disease. Genes with >1.2-fold upregulation and P<0.05 in OA VS HC were selected from the analysis.
2016-06-02 | E-GEOD-82107 | biostudies-arrayexpress
Project description:BackgroundOsteoarthritis (OA) is a slowly developing and debilitating disease, and there are no validated specific biomarkers for its early detection. To improve therapeutic approaches, identification of specific molecules/biomarkers enabling early determination of this disease is needed. This study aimed at identifying, with the use of proteomics/mass spectrometry, novel OA-specific serum biomarkers. As obesity is a major risk factor for OA, we discriminated obesity-regulated proteins to target only OA-specific proteins as biomarkers.MethodsSerum from the Osteoarthritis Initiative cohort was used and divided into 3 groups: controls (n=8), OA-obese (n=10) and OA-non-obese (n=10). Proteins were identified and quantified from the liquid chromatography-tandem mass spectrometry analyses using MaxQuant software. Statistical analysis used the Limma test followed by the Benjamini-Hochberg method. To compare the proteomic profiles, the multivariate unsupervised principal component analysis (PCA) followed by the pairwise comparison was used. To select the most predictive/discriminative features, the supervised linear classification model sparse partial least squares regression discriminant analysis (sPLS-DA) was employed. Validation of three differential proteins was performed with protein-specific assays using plasma from a cohort derived from the Newfoundland Osteoarthritis.ResultsIn total, 509 proteins were identified, and 279 proteins were quantified. PCA-pairwise differential comparisons between the 3 groups revealed that 8 proteins were differentially regulated between the OA-obese and/or OA-non-obese with controls. Further experiments using the sPLS-DA revealed two components discriminating OA from controls (component 1, 9 proteins), and OA-obese from OA-non-obese (component 2, 23 proteins). Proteins from component 2 were considered related to obesity. In component 1, compared to controls, 7 proteins were significantly upregulated by both OA groups and 2 by the OA-obese. Among upregulated proteins from both OA groups, some of them alone would not be a suitable choice as specific OA biomarkers due to their rather non-specific role or their strong link to other pathological conditions. Altogether, data revealed that the protein CRTAC1 appears to be a strong OA biomarker candidate. Other potential new biomarker candidates are the proteins FBN1, VDBP, and possibly SERPINF1. Validation experiments revealed statistical differences between controls and OA for FBN1 (p=0.044) and VDPB (p=0.022), and a trend for SERPINF1 (p=0.064).ConclusionOur study suggests that 4 proteins, CRTAC1, FBN1, VDBP, and possibly SERPINF1, warrant further investigation as potential new biomarker candidates for the whole OA population.
| S-EPMC9125906 | biostudies-literature
Project description:Inhibition of programmed death 1 (PD-1), expressed on activated T cells, can break through immune resistance and elicit durable responses in human melanoma as well as other types of cancers. Canine oral malignant melanoma is one of the most aggressive tumors bearing poor prognosis due to its high metastatic potency. However, there are few effective treatments for the advanced stages of melanoma in veterinary medicine. Only one previous study indicated the potential of the immune checkpoint inhibitor, anti-canine PD-L1 therapeutic antibody in dogs, and no anti-canine PD-1 therapeutic antibodies are currently available. Here, we developed two therapeutic antibodies, rat-dog chimeric and caninized anti-canine PD-1 monoclonal antibodies and evaluated in vitro functionality for these antibodies. Moreover, we conducted a pilot study to determine their safety profiles and clinical efficacy in spontaneously occurring canine cancers. In conclusion, the anti-canine PD-1 monoclonal antibody was relatively safe and effective in dogs with advanced oral malignant melanoma and other cancers. Thus, our study suggests that PD-1 blockade may be an attractive treatment option in canine cancers.
| S-EPMC7591904 | biostudies-literature
Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.
2022-06-23 | MSV000089716 | MassIVE
Project description: Not available
| S-EPMC10483499 | biostudies-literature
Project description:Osteoarthritis (OA) is a highly prevalent degenerative joint condition that disproportionately affects females. The pathophysiology of the disease is not well understood, which makes diagnosis and treatment difficult. Given the physical connection of synovial fluid (SF) with articular tissues, the SF's composition can reflect relevant biological modifications, and has therefore been a focus of research. Previously, we demonstrated that extracellular vesicles isolated from the synovial fluid of OA patients carry different cargo (protein and miRNA) in a sex-specific manner. Given the increased prevalence and severity of OA in females, this study aims to identify differential protein content within the synovial fluid of female OA and non-osteoarthritic (non-OA) patients. We found that several proteins were differentially expressed in osteoarthritic females compared with age-matched controls. Presenilin, Coagulation Factor X, Lysine-Specific Demethylase 2B, Tenascin C, Leucine-Rich Repeat-Containing Protein 17 fragments, and T-Complex Protein 1 were negatively regulated in the OA group, with PGD Synthase, Tubulointerstitial Nephritis Antigen, and Nuclear Receptor Binding SET Domain Protein 1 positively regulated in the OA group. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and QuickGO analyses established these proteins as significantly involved in many biological, cellular, and molecular processes. In conclusion, the protein content of female synovial fluid is altered in OA patients, which is likely to provide insights into gender-specific pathophysiology.
| S-EPMC10054440 | biostudies-literature