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      Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model

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      , , , ,
      BioMed Research International
      Hindawi

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          Abstract

          Introduction

          Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is the most common method, while stable MSU deposition enveloped by inflammatory cells was rarely reported.

          Objective

          To develop a modified gouty arthritis rat model characterized by intra-articular MSU deposition and continuous joint pain with a minimally invasive method.

          Method

          A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received intra-articular MSU embedment. Sham groups received pseudosurgeries with equal normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule were estimated. Mechanical pain threshold tests were conducted over a 96-hour period postoperatively. Moreover, quantitative immunofluorescence was conducted to assess tissue inflammation.

          Result

          After MSU embedding, rats got more persistent arthritic symptoms as well as tissue MSU deposition. More significant synovial swelling was detected in the MSU group compared to sham groups ( P < 0.025). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia during 2 hours to 96 hours postoperatively ( P < 0.05). MSU depositions enveloped by inflammatory cells that express IL-1 β and TNF- α were detected in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions upregulated expression of proinflammatory factors including IL-1 β and TNF- α ( P < 0.05).

          Conclusion

          A minimally invasive method was developed to establish modified rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of persistent gouty arthritis.

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          Most cited references35

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          Global epidemiology of gout: prevalence, incidence and risk factors.

          Gout is a crystal-deposition disease that results from chronic elevation of uric acid levels above the saturation point for monosodium urate (MSU) crystal formation. Initial presentation is mainly severely painful episodes of peripheral joint synovitis (acute self-limiting 'attacks') but joint damage and deformity, chronic usage-related pain and subcutaneous tophus deposition can eventually develop. The global burden of gout is substantial and seems to be increasing in many parts of the world over the past 50 years. However, methodological differences impair the comparison of gout epidemiology between countries. In this comprehensive Review, data from epidemiological studies from diverse regions of the world are synthesized to depict the geographic variation in gout prevalence and incidence. Key advances in the understanding of factors associated with increased risk of gout are also summarized. The collected data indicate that the distribution of gout is uneven across the globe, with prevalence being highest in Pacific countries. Developed countries tend to have a higher burden of gout than developing countries, and seem to have increasing prevalence and incidence of the disease. Some ethnic groups are particularly susceptible to gout, supporting the importance of genetic predisposition. Socioeconomic and dietary factors, as well as comorbidities and medications that can influence uric acid levels and/or facilitate MSU crystal formation, are also important in determining the risk of developing clinically evident gout.
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            Aggregated neutrophil extracellular traps limit inflammation by degrading cytokines and chemokines.

            Gout is characterized by an acute inflammatory reaction and the accumulation of neutrophils in response to monosodium urate (MSU) crystals. Inflammation resolves spontaneously within a few days, although MSU crystals can still be detected in the synovial fluid and affected tissues. Here we report that neutrophils recruited to sites of inflammation undergo oxidative burst and form neutrophil extracellular traps (NETs). Under high neutrophil densities, these NETs aggregate and degrade cytokines and chemokines via serine proteases. Tophi, the pathognomonic structures of chronic gout, share characteristics with aggregated NETs, and MSU crystals can induce NETosis and aggregation of NETs. In individuals with impaired NETosis, MSU crystals induce uncontrolled production of inflammatory mediators from neutrophils and persistent inflammation. Furthermore, in models of neutrophilic inflammation, NETosis-deficient mice develop exacerbated and chronic disease that can be reduced by adoptive transfer of aggregated NETs. These findings suggest that aggregated NETs promote the resolution of neutrophilic inflammation by degrading cytokines and chemokines and disrupting neutrophil recruitment and activation.
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              Gout: An old disease in new perspective – A review

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                Author and article information

                Contributors
                Journal
                Biomed Res Int
                Biomed Res Int
                BMRI
                BioMed Research International
                Hindawi
                2314-6133
                2314-6141
                2021
                8 June 2021
                : 2021
                : 6641701
                Affiliations
                Department of Sports Medicine, Huashan Hospital, Fudan University, No. 12 Urumqi Middle Rd., Shanghai 200040, China
                Author notes

                Academic Editor: Jun Zou

                Author information
                https://orcid.org/0000-0002-0767-1267
                Article
                10.1155/2021/6641701
                8208862
                34212036
                696977e9-bd4b-4ff6-ab4b-91a853fe3b46
                Copyright © 2021 Han-Lin Xu et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 December 2020
                : 28 May 2021
                Categories
                Research Article

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