A pilot study of microRNA assessment as a means to identify novel biomarkers of spontaneous osteoarthritis in dogs
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ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE212544 | GEO | 2022/09/04
REPOSITORIES: GEO
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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.
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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.
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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:Health monitoring during offshore saturation diving is complicated due to restricted access to the divers, the desire to keep invasive procedures to a minimum, and limited opportunity for laboratory work onboard dive support vessels (DSV). In this pilot study, we examined whether measuring salivary biomarkrers in samples collected by the divers themselves might be a feasible approach to environmental stress assessment. Nine saturation divers were trained in the passive drool method for saliva collection and proceeded to collect samples at nine time points before, during, and after an offshore commercial saturation diving campaign. Samples collected within the hyperbaric living chambers were decompressed and stored frozen at -20°C onboard the DSV until they were shipped to land for analysis. Passive drool samples were collected without loss and assayed for a selection of salivary biomarkers: secretory immunoglobulin A (SIgA), C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukins IL-6, IL-8, IL-1β, as well as cortisol and alpha-amylase. During the bottom phase of the hyperbaric saturation, SIgA, CRP, TNF-α, IL-8 and IL-1β increased significantly, whereas IL-6, cortisol and alpha-amylase were unchanged. All markers returned to pre-dive levels after the divers were decompressed back to surface pressure. We conclude that salivary biomarker analysis may be a feasible approach to stress assessment in offshore saturation diving. The results of our pilot test are consonant with an activation of the sympathetic nervous system related to systemic inflammation during hyperbaric and hyperoxic saturation.
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Project description:Little is known about the relationships of circulating levels of biomarkers of cartilage degradation with biomechanical outcomes relevant to knee osteoarthritis (OA) or biomarker changes following non-pharmacological interventions. The objectives of this exploratory, pilot study were to: 1) examine relationships between biomarkers of articular cartilage degradation and synthesis with measures of knee joint load during walking, and 2) examine changes in these biomarkers following 10 weeks of strengthening exercises.Seventeen (8 male, 9 female; 66.1 +/- 11.3 years of age) individuals with radiographically-confirmed medial tibiofemoral OA participated. All participants underwent a baseline testing session where serum and urine samples were collected, followed by a three-dimensional motion analysis. Motion analysis was used to calculate the external knee adduction moment (KAM) peak value and impulse. Following baseline testing, participants were randomized to either 10 weeks of: 1) physiotherapist-supervised lower limb muscle strengthening exercises, or 2) no exercises (control). Identical follow-up testing was conducted 11 weeks after baseline. Biomarkers included: urinary C-telopeptide of type II collagen (uCTX-II) and type II collagen cleavage neoepitope (uC2C), serum cartilage oligomeric matrix protein (sCOMP), serum hyaluronic acid (sHA) and serum C-propeptide of type II procollagen (sCPII). Linear regression analysis was used to examine relationships between measures of the KAM and biomarker concentrations as baseline, as well as between-group differences following the intervention.KAM impulse predicted significant variation in uCTX-II levels at baseline (p?=?0.04), though not when controlling for disease severity and walking speed (p?=?0.33). KAM impulse explained significant variation in the ratio uCTX-II;sCPII even when controlling for additional variables (p?=?0.04). Following the intervention, changes in sCOMP were significantly greater in the exercise group compared to controls (p?=?0.04). On average those in the control group experienced a slight increase in sCOMP and uCTX-II, while those in the exercise group experienced a reduction. No other significant findings were observed.This research provides initial evidence of a potential relationship between uCTX-II and knee joint load measures in patients with medial tibiofemoral knee OA. However, this relationship became non-significant after controlling for disease severity and walking speed, suggesting further research is necessary. It also appears that sCOMP is amenable to change following a strengthening intervention, suggesting a potential beneficial role of exercise on cartilage structure.Clinicaltrials.gov NCT01241812.
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Project description:More than 10% of babies are born too early resulting in over 15 million preterm births and more than one million new-born deaths globally. Although women with a previous spontaneous preterm birth (SPTB) are considered at high risk for recurrence, the majority occur in women without prior history. Prediction of SPTB risk allows for improved care and potential for targeting novel and existing therapeutics to prevent SPTB, which may result in improved outcomes for infant and mother. In this pilot study, a miRNA array was used to analyse plasma from healthy women in their first pregnancy at 20 weeks of gestation who then went on to deliver either at term or experience SPTB at 28-32 weeks. We identified specific miRNA expression profiles that differentiated between those mothers who delivered at term or delivered following SPTB. miR302b, miR1253 and a clustering of miR548 miRNAs were underexpressed in SPTB cases compared to term controls. Conversely, miR223 was elevated in mothers that later experienced a SPTB. The circulating miRNAs identified in the present study may therefore be attractive candidates as non-invasive biomarkers for the early prediction of SPTB. Further larger studies are now warranted to investigate the potential clinical utility of these markers.
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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.
2016-06-02 | GSE82107 | GEO