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Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

ABSTRACT: Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes.

SUBMITTER: Tsai JC

PROVIDER: S-EPMC7697780 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

Tsai Joseph C JC Casteneda Grant G Lee Abby A Dereschuk Kypros K Li Wei Tse WT Chakladar Jaideep J Lombardi Alecio F AF Ongkeko Weg M WM Chang Eric Y EY

International journal of molecular sciences 20201116 22

Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genom ...[more]

PMID: 33207573

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Project description:INTRODUCTION:The presence of leukocytes in platelet concentrates is deemed to cause deleterious effects when injected intra articularly. The aim of this study is to analyse both local and systemic effects induced by leukocyte-rich Platelet-rich Plasma (PRP) injections through a proteomic characterization of serial synovial fluid and blood samples obtained from subjects treated for knee OA. Secondary aim was to compare the effects on knee homeostasis and systemic response with those obtained with visco-supplementation. METHODS:Thirty-six OA patients treated either by autologous L-PRP or HA intra-articular knee injections, administered in series of three at one-week intervals, were analyzed. Just before the injection, 1 ml of synovial fluid was collected through the same needle way. In the same time, a peripheral blood sample was obtained and plasma separated. A further peripheral blood sample was collected at 2, 6, and 12 months. L-PRP, plasma and synovial fluid were tested by multiplex bead-based sandwich immunoassay by means of the Bio-Plex suspension array system (Bio-Rad Laboratories) for the presence of pro- and anti-inflammatory cytokines (IL-1beta, IL-6, IL-8, IL-17 and IL-4, IL-10, IL-13) and growth factors (FGF-b, HGF, PDGF-AB/BB). RESULTS:In general, pro-inflammatory cytokine levels were similar at basal condition and after treatment whereas anti-inflammatory ones were nearly undetectable. L-PRP administration did not modulate significant changes of cytokine concentrations either in synovial fluid or plasma, whatever the time points analyzed. No different trend was observed between L-PRP and HA administration in terms of pro- and anti-inflammatory cytokines, as well as growth factors. CONCLUSIONS:In contrast with the evidence reported by "in vitro" studies, where a cellular pro-inflammatory response appears to be induced by the presence of leukocytes, these results suggest that the presence leukocyte-rich PRP doesn't induce a relevant in vivo up regulation of pro-inflammatory mediators.

Project description:BackgroundIntra-articular (IA) corticosteroid (CS) injections are the mainstay of treatment for symptomatic management in knee osteoarthritis (OA), particularly in the UK. IA platelet-rich plasma (PRP) injections are a promising alternative, but no systematic reviews to date have compared them to the current standard of care, IA CS injections. We aim to investigate the effect of IA PRP injections versus IA corticosteroid injections for the symptomatic management of knee OA.MethodsAll published trials comparing IA PRP and CS injections for knee OA were included. MEDLINE, EMBASE, Scopus and Web of Science were searched through June 2020. Risk of bias was assessed using the Cochrane Risk of Bias tool. A random effects model was used to calculate standardized mean difference with 95% confidence interval in WOMAC/VAS score (or subscores), comparing IA PRP to CS injections across studies.ResultsIncluded were eight studies and 648 patients, 443 (68%) were female, mean age 59 years, with a mean BMI of 28.4. Overall, the studies were considered at low risk of bias. Compared with CS injections, PRP was significantly better in reducing OA symptoms (pain, stiffness, functionality) at 3, 6 and 9 months post-intervention (P < 0.01). The greatest effect was observed at 6 and 9 months (- 0.78 (- 1.34 to - 0.23) standard mean deviations (SMD) and - 1.63 (- 2.14 to - 1.12) SMD respectively). At 6 months, this equates to an additional reduction of 9.51 in WOMAC or 0.97 on the VAS pain scales. At 6 months PRP allowed greater return to sporting activities than CS, measured by the KOOS subscale for sporting activity, of magnitude 9.7 (- 0.45 to 19.85) (P = 0.06). Triple injections of PRP, generally separated by a week, were superior to single injections over 12 months follow-up (P < 0.01).ConclusionsIA-PRP injections produce superior outcomes when compared with CS injections for symptomatic management of knee OA, including improved pain management, less joint stiffness and better participation in exercise/sporting activity at 12 months follow-up. Giving three IA-PRP, with injections separated by a week, appears more effective than 1 IA-PRP injection.Prospero trial registration numberCRD42020181928 .

Project description:BackgroundThis work aimed to study the homing evidence and the reparative effect of mesenchymal stem cells (MSCs) in the healing process of induced osteoarthritis in experimental animal model (donkeys).MethodsTwenty-seven donkeys were equally divided into 3 groups based on the observation period after induction of arthritis (3, 6 and 9 weeks) to achieve different degrees of osteoarthritis. Each group was subdivided into three subgroups of three animals each based on the follow-up period (1, 2 and 6 months) after treatment. The induction was done through intra-articular (IA) injection of 2 ml of Amphotericin-B in both carpal joints. MSCs were harvested in a separate procedure, labeled with green fluorescent protein (GFP) using monster GFP vector and suspended in hyaluronic acid for IA injection. Treatment approaches consisted of cell-treatment using MSCs suspended in 3 ml of hyaluronic acid (HA) for the right carpal joint; and using the same amount of (HA) but without MSCs for the left contralateral carpal joint to serve as a control. Animals were assessed clinically and radiologically before and after treatment. Synovial fluid was also evaluated. Histopathologically; articular cartilage structural changes, reduction of articular cartilage matrix staining, osteophyte formation, and subchondral bone plate thickening were graded. Data was summarized using median and percentile for scores of histopathologic grading. Comparison between groups was done using non-parametric Mann Whitney test.ResultsThe reparative effect of MSCs was significant both clinically and radiologically in all treated groups (P < 0.05) compared to the control groups. Fluorescence microscopy of sections of the cell-treated joints of all animals indicated that the GFP-transduced injected cells have participated effectively in the reparative process of the damaged articular surface and have integrated within the existing articular cartilage. The cells were associated with the surface of the cartilage and, were also detected in the interior.ConclusionsHoming was confirmed by the incorporation of injected GFP-labeled MSCs within the repaired newly formed cartilage. Significant recovery proves that the use of IA injection of autologous MSCs is a viable and a practical option for treating different degrees of osteoarthritis.

Project description:BackgroundThe increasing demand for total knee arthroplasty (TKR) and the initiatives to reduce health care spending have put the responsibility for efficient care on hospitals and providers. Multidisciplinary care pathways have been shown to shorten length of stay and result in improved short-term outcomes. However, common problems such as post-op nausea, orthostasis, and quad weakness remain, while reliance on discharge to rehabilitation facilities may also prolong hospital stay.Questions/purposesOur aim was to document that combined modifications of our traditional clinical pathway for unilateral TKR could lead to improved short-term outcomes. We pose the following research questions. Can pathway modifications which include intra-articular infusion and saphenous nerve block (SNB) provide adequate pain relief and eliminate common side effects promoting earlier mobilization? Can planning for discharge to home avoid in-patient rehab stays? Can these combined modifications decrease length of stay even in patients with complex comorbidities indicated by higher ASA class? Will discharge to home incur an increase in complications or a failure to achieve knee range of motion?Patients and methodsA retrospective review was performed and identified two cohorts. Group A included 116 patients that underwent unilateral TKR for osteoarthritis between August 2009 and August 2010. Group B included 171 patients that underwent unilateral TKR for osteoarthritis between February 2012 to February 2013. Group A patients were treated with spinal anesthesia with patient-controlled epidural analgesia (PCEA)/femoral nerve block (FNB) for the first 48 h after surgery. Discharge planning was initiated after admission. Group B had spinal anesthesia with SNB and received a continuous intra-articular infusion of 0.2% ropivicaine for 48 h post-op. Discharge planning was initiated with a case manager prior to hospitalization and discharge to home was declared the preferred approach. An intensive home PT program was made available through a program with our local home care agency. Outcomes assessed and compared between groups included length of stay, incidence of post-op nausea, dizziness, in-hospital falls, occurrence of complications including wound infection and the recovery of range of motion at 6 weeks, 3 months, and 1 year post-op.ResultsPain control was similar between the groups but Group B had fewer side effects. With the new pathway, length of stay (LOS) was reduced from 4.32 to 3.64 days with a similar LOS reduction across all ASA classes. There was no increase in Group B wound or other complications. Return of ROM was similar between groups.ConclusionsOur findings suggest that replacing PCEA and FNB with intra-articular analgesia with a SNB allows for improved early recovery following TKR. That, combined with pre-op discharge planning and initiation of an intensive home PT program, reduced average length of stay.

Project description:INTRODUCTION:Intra-articular (IA) injection of hyaluronic acid (HA) and corticosteroid (CS) is a common treatment for osteoarthritis (OA) of the knee. As a drug treatment for patients with depression, duloxetine has been shown in many studies to effectively relieve the pain of OA and improve function of the knee joint. However, evidence regarding the efficacy of IA injection of HA+CS combined with duloxetine for pain management in patients with OA of the knee is lacking. The aim of this study was to test the hypothesis that IA injection of HA+CS combined with duloxetine could achieve pain management superior to that of IA injection of HA+CS alone in patients experiencing knee OA pain. METHODS:This study will adopt a prospective, randomised, open-label blind endpoint study design. In total, 150 patients with OA of the knee will be enrolled in the study. The participants will be randomly allocated to receive either a single IA injection of HA+CS combined with duloxetine or a single IA injection of HA+CS alone, and both groups will complete a 24-week follow-up to assess pain and functional improvements. The primary outcome measure is the change in the weekly mean of the 24?hours average pain scores from baseline to the end of 24 weeks in patients with OA of the knee, and the secondary outcomes include the response to treatment, changes from baseline in the brief pain inventory, improvement in the Western Ontario and McMaster Universities Osteoarthritis index scores, patient global impression of improvement scale, Hospital Anxiety and Depression Scale and adverse events during the 24-week follow-up. The data will be analysed by the intention-to-treat principle. ETHICS APPROVAL AND DISSEMINATION:This study was approved by the institutional ethics committee of the Beijing Tiantan Hospital (approval number: KY 2019-086-02). The results of the study will be published in peer-reviewed journals, and the findings will be presented at scientific meetings. TRIAL REGISTRATION NUMBER:ClinicalTrials.gov Identifier: NCT04117893; Pre-results.

Dataset Information

Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

Publications

Identification and Characterization of the Intra-Articular Microbiome in the Osteoarthritic Knee.

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