Construction and evaluation of a chronic arthritis animal model induced by persistent activation of toll‐like receptors via lipopolysaccharide stimulation
Abstract
Abstract Background Systemic juvenile idiopathic arthritis (sJIA) is a chronic arthritis characterized primarily by systemic inflammatory responses. However, its pathogenesis remains incompletely understood and may be related to the activation of Toll‐like receptors (TLRs). To overcome limitations of existing models, this study develops an animal model mimicking sJIA systemic inflammatory features via TLR4 activation. Methods We integrated multi‐center single‐cell and bulk RNA‐seq data from sJIA patients and healthy children to assess TLR pathway activity. Based on the analysis of differentially expressed TLR molecules, we identified TLR4 as an important factor. A chronic arthritis mouse model (LC) was constructed by introducing sustained TLR4 activation into the collagen‐induced arthritis (CIA) model. The general condition, inflammation, and joint pathology were evaluated. Results In sJIA patients, TLR pathway activation, particularly in monocytes, was identified as a key feature. Bulk RNA‐seq analysis revealed TLR4 expression was significantly upregulated in sJIA. The LC mouse model exhibited pronounced systemic inflammation, including fever, weight loss, splenomegaly, and elevated inflammatory cytokines (IL‐18, TNF‐α, IFN‐γ). Immunofluorescence confirmed significant CD163+ macrophage infiltration in the liver of LC mice. Interestingly, despite the exacerbated systemic inflammation, the LC mice exhibited milder joint damage, lower arthritis scores, and less cartilage…
Read the paper
Related studies
- Improving the translation of search strategies using the Polyglot Search Translator: a randomized controlled trial
- Nutritional, Physical, Cognitive, and Combination Interventions and Frailty Reversal Among Older Adults: A Randomized Controlled Trial
- Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study
- A randomized, controlled trial of oral propranolol in infantile hemangioma
- Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study
- Increased physical activity improves sleep and mood outcomes in inactive people with insomnia: a randomized controlled trial
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.