Moderate Exercise Protects Against Joint Disease in a Murine Model of Osteoarthritis

Abstract Exercise is recommended as a non-pharmacological therapy for osteoarthritis (OA). Clinical studies investigating the impact of exercise on OA have primarily focussed on the assessment of joint pain and mobilisation, where positive outcomes have been demonstrated. Clinical imaging studies provide limited information on the impact of exercise (positive or negative) on the actual bone and soft tissue pathology. Various exercise regimes, with differing intensities and duration, have been used in a range of OA models, with disparate results. The present study provides definitive insight into the effect of moderate exercise on early joint pathology in the destabilisation of the medial meniscus (DMM) mouse model of OA. Exercise was induced by forced treadmill walking for 3 or 7 weeks. Joints were analysed by microcomputed tomography and histology. Exercise offered protection against cartilage damage and joint inflammation, and a temporary protection against osteosclerosis. Furthermore, exercise modified the metaphyseal trabecular microarchitecture of the osteoarthritic leg. Collectively, our findings provide scientific support for the clinical recommendation of moderate exercise as a physical therapy in OA. In addition to indirect benefit via positive physiological effects of weight loss, our data suggest direct short-term benefits in ameliorating pathology of cartilage, synovitis and bone.

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Cytohesin-2/ARNO: A Novel Bridge Between Cell Migration and Immunoregulation in Synovial Fibroblasts

Frontiers in Immunology ◽

10.3389/fimmu.2021.809896 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yilin Wang ◽

Çağlar Çil ◽

Margaret M. Harnett ◽

Miguel A. Pineda

Keyword(s):

Cell Migration ◽

Inflammatory Responses ◽

Cartilage Damage ◽

Focal Adhesions ◽

Synovial Fibroblasts ◽

Small Gtpase ◽

Joint Disease ◽

Cell Phenotype ◽

Small Interference Rna ◽

The Impact

The guanine nucleotide exchange factor cytohesin-2 (ARNO) is a major activator of the small GTPase ARF6 that has been shown to play an important role(s) in cell adhesion, migration and cytoskeleton reorganization in various cell types and models of disease. Interestingly, dysregulated cell migration, in tandem with hyper-inflammatory responses, is one of the hallmarks associated with activated synovial fibroblasts (SFs) during chronic inflammatory joint diseases, like rheumatoid arthritis. The role of ARNO in this process has previously been unexplored but we hypothesized that the pro-inflammatory milieu of inflamed joints locally induces activation of ARNO-mediated pathways in SFs, promoting an invasive cell phenotype that ultimately leads to bone and cartilage damage. Thus, we used small interference RNA to investigate the impact of ARNO on the pathological migration and inflammatory responses of murine SFs, revealing a fully functional ARNO-ARF6 pathway which can be rapidly activated by IL-1β. Such signalling promotes cell migration and formation of focal adhesions. Unexpectedly, ARNO was also shown to modulate SF-inflammatory responses, dictating their precise cytokine and chemokine expression profile. Our results uncover a novel role for ARNO in SF-dependent inflammation, that potentially links pathogenic migration with initiation of local joint inflammation, offering new approaches for targeting the fibroblast compartment in chronic arthritis and joint disease.

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Undenatured Type II Collagen Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rat Model of Osteoarthritis

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.617789 ◽

2021 ◽

Vol 8 ◽

Author(s):

Cemal Orhan ◽

Vijaya Juturu ◽

Emre Sahin ◽

Mehmet Tuzcu ◽

Ibrahim Hanifi Ozercan ◽

...

Keyword(s):

Articular Cartilage ◽

Inflammatory Responses ◽

Cartilage Damage ◽

Joint Inflammation ◽

Type Ii Collagen ◽

Serum Levels ◽

Joint Disease ◽

Type Ii ◽

Age Related ◽

Undenatured Type Ii Collagen

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.

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GEF Cytohesin-2/ARNO: a novel bridge between cell migration and immunoregulation in synovial fibroblasts

10.1101/2021.10.04.463120 ◽

2021 ◽

Author(s):

Yilin Wang ◽

Çağlar Çil ◽

Margaret M. Harnett ◽

Miguel A. Pineda

Keyword(s):

Cell Migration ◽

Inflammatory Responses ◽

Cartilage Damage ◽

Focal Adhesions ◽

Synovial Fibroblasts ◽

Small Gtpase ◽

Joint Disease ◽

Cell Phenotype ◽

Small Interference Rna ◽

The Impact

AbstractThe guanine nucleotide exchange factor cytohesin-2 (ARNO) is a major activator of the small GTPase ARF6, and has been shown to play an important role(s) in cell adhesion, migration and cytoskeleton reorganization in various cell types and models of disease. Interestingly, dysregulated cell migration, in tandem with hyper-inflammatory responses, is one of the hallmarks associated with activated synovial fibroblasts (SFs) during chronic inflammatory joint diseases, like rheumatoid arthritis. The role of ARNO in this process was unknown but we hypothesized that the pro-inflammatory milieu of inflamed joints induces local activation of ARNO-mediated pathways in SFs, promoting an invasive cell phenotype that ultimately leads to bone and cartilage damage. Thus, we used small interference RNA to investigate the impact of ARNO on the pathological migration and inflammatory responses of murine SFs, revealing a fully functional ARNO-ARF6 pathway in SFs, which can be rapidly activated by IL-1β. Such activation promotes cell migration and formation of focal adhesions. Unexpectedly, ARNO was also shown to modulate SF-inflammatory responses, dictating the precise cytokine and chemokine expression profile. Our results uncover a novel role for ARNO in SF-dependent inflammation, that potentially links pathogenic migration with initiation of local joint inflammation, offering new approaches for targeting the fibroblast compartment in chronic arthritis and joint disease.

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The Gut Microbiota of Rats under Experimental Osteoarthritis and Administration of Chondroitin Sulfate and Probiotic

Mikrobiolohichnyi Zhurnal ◽

10.15407/microbiolj82.06.064 ◽

2020 ◽

Vol 82 (6) ◽

pp. 64-73

Author(s):

O.H. Korotkyi ◽

◽

T.V. Luhovska ◽

T.M. Serhiychuk ◽

K.O. Dvorshchenko ◽

...

Keyword(s):

Gut Microbiota ◽

Chondroitin Sulfate ◽

Joint Inflammation ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Quantitative Composition ◽

Combined Administration ◽

Osteoarthritis Progression ◽

Experimental Osteoarthritis ◽

Gut Microbiota Composition

Osteoarthritis is a most widespread chronic degenerative joint disease that causes pain, cartilage deformation, and joint inflammation. Adverse alterations of intestinal microbiota like dysbiosis may lead to metabolic syndrome and inflammation, two important components of osteoarthritis progression. Aim. In this study we investigated the effect of chondroitin sulfate and probiotics on the gut microbiome in monoiodoacetate-induced osteoarthritis model in rats. Methods. The species and quantitative composition of feces were determined using diagnostic media with selective properties. Further identification of isolated microorganisms was carried out according to morphological, tinctorial, physiological and metabolic parameters. The results are presented in the form of lg CFU/g. Results. Induction of osteoarthritis caused significant increasing the number of opportunistic enterobacteria and lactose-negative Escherichia coli against the decreasing of lacto- and bifidobacteria that may indicate a dysbiotic condition. Coadministration of chondroitin sulfate and probiotic bacteria has led to improvement the quantitative composition of the gut microbiota in experimental animals, the numerous of Bifidobacterium, Lactobacillus were increasing against decreasing the quantitative composition of opportunistic microorganisms. Conclusions. Monoiodoacetate-induced osteoarthritis caused dysbiosis of gut in rat. We observed beneficial effect of combined administration of chondroitin sulfate and probiotics on gut microbiota composition in rats with experimental osteoarthritis. Thus, adding of supplements like probiotics to standard treatment of osteoarthritis may have potentials to prevent and treat this disease.

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Simulation of the Impact of Higher Ammonia Recycle Loads Caused by Upgrading Anaerobic Sludge Digesters

Water Quality Research Journal ◽

10.2166/wqrj.2005.053 ◽

2005 ◽

Vol 40 (4) ◽

pp. 491-499 ◽

Cited By ~ 2

Author(s):

Jeremy T. Kraemer ◽

David M. Bagley

Keyword(s):

Anaerobic Digestion ◽

Biogas Production ◽

Treatment Plant ◽

Anaerobic Sludge ◽

Content Increase ◽

Limited Information ◽

Dynamic Simulations ◽

Treatment Train ◽

Temperature Liquid ◽

The Impact

Abstract Upgrading conventional single-stage mesophilic anaerobic digestion to an advanced digestion technology can increase sludge stability, reduce pathogen content, increase biogas production, and also increase ammonia concentrations recycled back to the liquid treatment train. Limited information is available to assess whether the higher ammonia recycle loads from an anaerobic sludge digestion upgrade would lead to higher discharge effluent ammonia concentrations. Biowin, a commercially available wastewater treatment plant simulation package, was used to predict the effects of anaerobic digestion upgrades on the liquid train performance, especially effluent ammonia concentrations. A factorial analysis indicated that the influent total Kjeldahl nitrogen (TKN) and influent alkalinity each had a 50-fold larger influence on the effluent NH3 concentration than either the ambient temperature, liquid train SRT or anaerobic digestion efficiency. Dynamic simulations indicated that the diurnal variation in effluent NH3 concentration was 9 times higher than the increase due to higher digester VSR. Higher recycle NH3 loads caused by upgrades to advanced digestion techniques can likely be adequately managed by scheduling dewatering to coincide with periods of low influent TKN load and ensuring sufficient alkalinity for nitrification.

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Psychological Impacts of COVID-19 During the First Nationwide Lockdown in Vietnam: Web-Based, Cross-Sectional Survey Study (Preprint)

10.2196/preprints.24776 ◽

2020 ◽

Author(s):

Khanh Ngoc Cong Duong ◽

Tien Nguyen Le Bao ◽

Phuong Thi Lan Nguyen ◽

Thanh Vo Van ◽

Toi Phung Lam ◽

...

Keyword(s):

Psychological Distress ◽

General Population ◽

Psychological Health ◽

Online Survey ◽

Survey Study ◽

Limited Information ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Event Scale ◽

The Impact

BACKGROUND The first nationwide lockdown due to the COVID-19 pandemic was implemented in Vietnam from April 1 to 15, 2020. Nevertheless, there has been limited information on the impact of COVID-19 on the psychological health of the public. OBJECTIVE This study aimed to estimate the prevalence of psychological issues and identify the factors associated with the psychological impact of COVID-19 during the first nationwide lockdown among the general population in Vietnam. METHODS We employed a cross-sectional study design with convenience sampling. A self-administered, online survey was used to collect data and assess psychological distress, depression, anxiety, and stress of participants from April 10 to 15, 2020. The Impact of Event Scale-Revised (IES-R) and the Depression, Anxiety, and Stress Scale-21 (DASS-21) were utilized to assess psychological distress, depression, anxiety, and stress of participants during social distancing due to COVID-19. Associations across factors were explored using regression analysis. RESULTS A total of 1385 respondents completed the survey. Of this, 35.9% (n=497) experienced psychological distress, as well as depression (n=325, 23.5%), anxiety (n=195, 14.1%), and stress (n=309, 22.3%). Respondents who evaluated their physical health as average had a higher IES-R score (beta coefficient [B]=9.16, 95% CI 6.43 to 11.89), as well as higher depression (B=5.85, 95% CI 4.49 to 7.21), anxiety (B=3.64, 95% CI 2.64 to 4.63), and stress (B=5.19, 95% CI 3.83 to 6.56) scores for DASS-21 than those who rated their health as good or very good. Those who self-reported their health as bad or very bad experienced more severe depression (B=9.57, 95% CI 4.54 to 14.59), anxiety (B=7.24, 95% CI 3.55 to 10.9), and stress (B=10.60, 95% CI 5.56 to 15.65). Unemployment was more likely to be associated with depression (B=3.34, 95% CI 1.68 to 5.01) and stress (B=2.34, 95% CI 0.84 to 3.85). Regarding worries about COVID-19, more than half (n=755, 54.5%) expressed concern for their children aged <18 years, which increased their IES-R score (B=7.81, 95% CI 4.98 to 10.64) and DASS-21 stress score (B=1.75, 95% CI 0.27 to 3.24). The majority of respondents (n=1335, 96.4%) were confident about their doctor’s expertise in terms of COVID-19 diagnosis and treatment, which was positively associated with less distress caused by the outbreak (B=–7.84, 95% CI –14.58 to –1.11). CONCLUSIONS The findings highlight the effect of COVID-19 on mental health during the nationwide lockdown among the general population in Vietnam. The study provides useful evidence for policy decision makers to develop and implement interventions to mitigate these impacts. CLINICALTRIAL

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Small Noncoding RNAs in Knee Osteoarthritis: The Role of MicroRNAs and tRNA-Derived Fragments

International Journal of Molecular Sciences ◽

10.3390/ijms22115711 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5711

Author(s):

Julian Zacharjasz ◽

Anna M. Mleczko ◽

Paweł Bąkowski ◽

Tomasz Piontek ◽

Kamilla Bąkowska-Żywicka

Keyword(s):

Knee Osteoarthritis ◽

Noncoding Rnas ◽

Pathological Process ◽

Joint Disease ◽

Limited Information ◽

Genetic Changes ◽

Small Noncoding Rnas ◽

Knee Oa ◽

Cartilage Homeostasis

Knee osteoarthritis (OA) is a degenerative knee joint disease that results from the breakdown of joint cartilage and underlying bone, affecting about 3.3% of the world's population. As OA is a multifactorial disease, the underlying pathological process is closely associated with genetic changes in articular cartilage and bone. Many studies have focused on the role of small noncoding RNAs in OA and identified numbers of microRNAs that play important roles in regulating bone and cartilage homeostasis. The connection between other types of small noncoding RNAs, especially tRNA-derived fragments and knee osteoarthritis is still elusive. The observation that there is limited information about small RNAs different than miRNAs in knee OA was very surprising to us, especially given the fact that tRNA fragments are known to participate in a plethora of human diseases and a portion of them are even more abundant than miRNAs. Inspired by these findings, in this review we have summarized the possible involvement of microRNAs and tRNA-derived fragments in the pathology of knee osteoarthritis.

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The Rationale for the Intra-Articular Administration of Clodronate in Osteoarthritis

International Journal of Molecular Sciences ◽

10.3390/ijms22052693 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2693

Author(s):

Antimo Moretti ◽

Marco Paoletta ◽

Sara Liguori ◽

Walter Ilardi ◽

Francesco Snichelotto ◽

...

Keyword(s):

Animal Models ◽

Scoping Review ◽

Cartilage Damage ◽

Joint Inflammation ◽

Mechanisms Of Action ◽

Clodronic Acid ◽

Clinical Role ◽

Knee Oa ◽

Positive Effects ◽

Scoping Reviews

Background: Several pharmacological therapeutic approaches have been proposed to manage osteoarthritis (OA), including intra-articular (IA) injections. Although the discovery of clodronate, a bisphosphonate, dates back to the 1960s and the effects of its IA administration have been investigated for decades in animal models, mechanisms of action of this drug are not quite clear, particularly in OA. This scoping review is an overview of the biological as well as the clinical role of clodronic acid in OA. Method: A scoping review based on the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model was performed to characterize the mechanisms of action of IA clodronate in OA and to evaluate its efficacy from a clinical point of view. Results: Several effects of clodronate have been observed in animal models of OA, including depletion of synovial lining cells that results in reduced production of chemokines (IL-1, TNF- α), growth factors (TGF-β, BMP 2/4), and metalloproteases (MMP 2/3/9); prevention of cartilage damage, synovial hyperplasia, and proteoglycans loss; reduction in joint inflammation, joint swelling, and osteophyte formation. From a clinical perspective, patients with knee OA treated with IA clodronate experienced improvements in pain and joint mobility. Conclusion: Clodronate appears to have different mechanisms of action interfering with the pathogenic processes contributing to OA development and progression. This intervention demonstrated positive effects for patients affected by knee OA.

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The Impact of Alzheimer’s Disease and Related Dementias on Dental Care Utilization and Costs in Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.2903 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 800-800

Author(s):

Sam Li ◽

Isaac Donkor ◽

Liang Hong ◽

Kevin Lu ◽

Bei Wu

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dental Care ◽

Negative Binomial ◽

Self Report ◽

Care Utilization ◽

Limited Information ◽

Dental Care Utilization ◽

The Impact ◽

Care Costs

Abstract There is limited information on the impact of cognition function on dental care utilization and costs. This study used the Medicare current beneficiaries survey in 2016 and included 4,268 participants 65+. Dental care utilization and costs were measured by self-report and included preventive and treatment events. Negative binomial regression and generalized linear regression were used to examine the impact of Alzheimer’s disease (AD) and related dementia (RD) on dental care utilization and costs. We found that AD was not associated with dental care utilization, but RD was associated with a lower number of total treatment dental care visits (IRR: 0.60; 95% CI: 0.37~0.98). RD was not associated with dental care costs, but AD was associated with higher total dental care costs (estimate: 1.08; 95% CI: 0.14~2.01) and higher out-of-pocket costs (estimate: 1.25; 95% CI: 0.17~2.32). AD and RD had different impacts on different types of dental care utilization and costs. Part of a symposium sponsored by the Oral Health Interest Group.

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The Impact of Interruptions on Feature Change Detection within Dynamic Scenes

Proceedings of the Human Factors and Ergonomics Society Annual Meeting ◽

10.1177/1071181319631240 ◽

2019 ◽

Vol 63 (1) ◽

pp. 1430-1434

Author(s):

Kimberly N. Perry ◽

Mark W. Scerbo

Keyword(s):

Working Memory ◽

Situation Awareness ◽

Specific Information ◽

Limited Information ◽

Dynamic Scenes ◽

Feature Change ◽

Activation Level ◽

Level 1 ◽

Perceptual Changes ◽

The Impact

The goal of the present study was to examine how interruptions occurring in dynamic scenes affect the ability to detect perceptual changes during level 1 situation awareness (SA). Undergraduates were asked to watch 24 brief videos (half with interruptions) including 8 with perceptual feature changes. All videos were unique and contained multiple dynamic objects. Three different sets of instructions regarding the changes were given to successive groups: no information, limited information, and feature specific information. Of the eight changes, half occurred during a visual interruption and half with no interruption. Results showed that participants detected few changes, but detections increased when given more information about the nature of the changes in the absence of interruptions. The findings suggest that interruptions may facilitate the decay of an objects’ activation level in working memory and that level 1 SA may be particularly fragile when the visual scene is interrupted.

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