Crystal-Induced Arthritis: Pathogenetic Mechanisms and Clinical Advances

Topic Information

Dear Colleagues,

Crystal-induced arthritis represents one of the most common joint diseases worldwide. The inflammatory process, which is triggered by pathogenic crystals, including urate and calcium crystals, causes intense acute attacks with pain and systemic inflammatory symptoms. When left untreated, this condition leads to irreversible joint damage. Given its unique features, including its abrupt onset and spontaneous resolution, crystal-induced arthritis has represented a fascinating model of acute inflammation for years. In the last two decades, experimental and translational research in this field has contributed to improving our knowledge on the molecular mechanisms that are associated with different disease phases and to expand the pharmacological options for patients. Thus, the identification of IL-1β as the most important cytokine that orchestrates crystal-induced inflammation, especially in gout- and pyrophosphate calcium crystal-related flare-ups, has provided new therapeutic options for patients who are not responsive or who present important side effects to traditional therapies. Despite the progress that has been made so far, unmet needs persist in this field and are mainly linked to calcium crystal-deposition diseases. The lack of effective treatments makes calcium-related arthropathies a challenging area that certainly needs further and future advances. With this Topic, we would like to invite authors to contribute original research articles as well as review articles focused on recent findings on the mechanisms, clinical and genetic aspects, prevention, and management of crystal-induced arthritis.

Dr. Francesca Oliviero
Dr. Hang Korng Ea
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900
Journal of Clinical Medicine jcm	3.0	5.7	2012	16 Days	CHF 2600
Journal of Personalized Medicine jpm	-	4.1	2011	17.4 Days	CHF 2600
Medicina medicina	2.4	3.3	1920	17.1 Days	CHF 2200
Rheumato rheumato	-	-	2021	26.7 Days	CHF 1000

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Published Papers (3 papers)

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Open AccessArticle

Establishment and Validation of Predictive Model of Tophus in Gout Patients

by Tianyi Lei, Jianwei Guo, Peng Wang, Zeng Zhang, Shaowei Niu, Quanbo Zhang and Yufeng Qing

J. Clin. Med. 2023, 12(5), 1755; https://doi.org/10.3390/jcm12051755 - 22 Feb 2023

Cited by 15 | Viewed by 4950

Abstract

(1) Background: A tophus is a clinical manifestation of advanced gout, and in some patients could lead to joint deformities, fractures, and even serious complications in unusual sites. Therefore, to explore the factors related to the occurrence of tophi and establish a prediction [...] Read more.

(1) Background: A tophus is a clinical manifestation of advanced gout, and in some patients could lead to joint deformities, fractures, and even serious complications in unusual sites. Therefore, to explore the factors related to the occurrence of tophi and establish a prediction model is clinically significant. (2) Objective: to study the occurrence of tophi in patients with gout and to construct a predictive model to evaluate its predictive efficacy. (3) Methods: The clinical data of 702 gout patients were analyzed by using cross-sectional data of North Sichuan Medical College. The least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used to analyze predictors. Multiple machine learning (ML) classification models are integrated to analyze and identify the optimal model, and Shapley Additive exPlanations (SHAP) interpretation was developed for personalized risk assessment. (4) Results: Compliance of urate-lowering therapy (ULT), Body Mass Index (BMI), course of disease, annual attack frequency, polyjoint involvement, history of drinking, family history of gout, estimated glomerular filtration rate (eGFR), and erythrocyte sedimentation rate (ESR) were the predictors of the occurrence of tophi. Logistic classification model was the optimal model, test set area under curve (AUC) (95% confidence interval, CI): 0.888 (0.839–0.937), accuracy: 0.763, sensitivity: 0.852, and specificity: 0.803. (5) Conclusions: We constructed a logistic regression model and explained it with the SHAP method, providing evidence for preventing tophus and guidance for individual treatment of different patients. Full article

(This article belongs to the Topic Crystal-Induced Arthritis: Pathogenetic Mechanisms and Clinical Advances)

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14 pages, 1426 KiB  

Open AccessArticle

Osteogenic Potential of Monosodium Urate Crystals in Synovial Mesenchymal Stem Cells

by Karina Martínez-Flores, Ricardo Plata-Rodríguez, Anell Olivos-Meza, Ambar López-Macay, Javier Fernández-Torres, Carlos Landa-Solís and Yessica Zamudio-Cuevas

Medicina 2022, 58(12), 1724; https://doi.org/10.3390/medicina58121724 - 24 Nov 2022

Cited by 1 | Viewed by 2066

Abstract

Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem [...] Read more.

Background and Objectives: Deposits of monosodium urate (MSU) crystals due to increased levels of uric acid (UA) have been associated with bone formation and erosion, mainly in patients with chronic gout. The synovial membrane (SM) comprises several types of cells, including mesenchymal stem cells (SM-MSCs); however, it is unknown whether UA and MSU induce osteogenesis through SM-MSCs. Materials and Methods: Cultures of SM were immunotyped with CD44, CD69, CD90, CD166, CD105, CD34, and CD45 to identify MSCs. CD90+ cells were isolated by immunomagnetic separation (MACS), colony-forming units (CFU) were identified, and the cells were exposed to UA (3, 6.8, and 9 mg/dL) and MSU crystals (1, 5, and 10 μg/mL) for 3 weeks, and cellular morphological changes were evaluated. IL-1β and IL-6 were determined by ELISA, mineralization was assessed by alizarin red, and the expression of Runx2 was assessed by Western blot. Results: Cells derived from SM and after immunomagnetic separation were positive for CD90 (53 ± 8%) and CD105 (52 ± 18%) antigens, with 53 ± 5 CFU identified. Long-term exposure to SM-MSCs by UA and MSU crystals did not cause morphological damage or affect cell viability, nor were indicators of inflammation detected. Mineralization was observed at doses of 6.8 mg/dL UA and 5 μg/mL MSU crystals; however, the differences were not significant with respect to the control. The highest dose of MSU crystals (10 μg/mL) induced significant Runx2 expression with respect to the control (1.4 times greater) and SM-MSCs cultured in the osteogenic medium. Conclusions: MSU crystals may modulate osteogenic differentiation of SM-MSCs through an increase in Runx2. Full article

(This article belongs to the Topic Crystal-Induced Arthritis: Pathogenetic Mechanisms and Clinical Advances)

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Open AccessArticle

The Association between Serum Testosterone and Hyperuricemia in Males

by Meng-Ko Tsai, Kuang-Chen Hung, Chun-Cheng Liao, Lung-Fa Pan, Chia-Lien Hung and Deng-Ho Yang

J. Clin. Med. 2022, 11(10), 2743; https://doi.org/10.3390/jcm11102743 - 12 May 2022

Cited by 10 | Viewed by 3142

Abstract

Gout is a common systemic inflammatory disease with a male predominance. This study aimed to determine the relationship between serum total testosterone level and hyperuricemia. Data on 1899 men, collected from 2007 to 2017, were included in the analysis. Serum testosterone and urate [...] Read more.

Gout is a common systemic inflammatory disease with a male predominance. This study aimed to determine the relationship between serum total testosterone level and hyperuricemia. Data on 1899 men, collected from 2007 to 2017, were included in the analysis. Serum testosterone and urate (SU) were measured on enrolment. The primary endpoints were SU levels ≥ 7 mg/dL and ≥9 mg/dL. On enrolment, participants had a mean age of 45.6 years and mean total testosterone and SU levels of 510 ng/dL and 6.6 mg/dL, respectively. The mean total testosterone levels were 533 and 470 ng/dL in patients with SU levels < 7 mg/dL and ≥7 mg/dL, respectively (p < 0.001); and 515 and 425 ng/dL in patients with SU levels < 9 mg/dL and ≥9 mg/dL, respectively (p < 0.001). After adjusting for age, body mass index, creatinine, serum lipid, fasting blood glucose, systolic blood pressure, and diastolic blood pressure, low testosterone level (<400 ng/dL) was significantly associated with an SU level ≥ 7 mg/dL (hazard ratio: 1.182, 95% confidence interval: 1.005–1.39) and ≥9 mg/dL (hazard ratio: 1.905, 95% confidence interval: 1.239–2.928). In men, a low testosterone level may be associated with an increased risk of hyperuricemia. Full article

(This article belongs to the Topic Crystal-Induced Arthritis: Pathogenetic Mechanisms and Clinical Advances)

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