RT Journal Article
SR Electronic
T1 Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP annrheumdis-2022-222764
DO 10.1136/ard-2022-222764
A1 HanLin Xu
A1 Bohan Zhang
A1 Yaxin Chen
A1 Fengzhen Zeng
A1 Wenjuan Wang
A1 Ziyi Chen
A1 Ling Cao
A1 Jun Shi
A1 Jun Chen
A1 Xiaoxia Zhu
A1 Yu Xue
A1 Rui He
A1 MinBiao Ji
A1 YingHui Hua
YR 2022
UL http://ard.bmj.com/content/early/2022/09/23/ard-2022-222764.abstract
AB Objective Increasing evidence suggests that impaired cartilage is a substantial risk factor for the progression from hyperuricaemia to gout. Since the relationship between cartilage matrix protein and gout flares remains unclear, we investigated its role in monosodium urate (MSU) crystallisation and following inflammation.Methods Briefly, we screened for cartilage matrix in synovial fluid from gouty arthritis patients with cartilage injuries. After identifying a correlation between crystals and matrix molecules, we conducted image analysis and classification of crystal phenotypes according to their morphology. We then evaluated the differences between the cartilage matrix protein-MSU complex and the pure MSU crystal in their interaction with immune cells and identified the related signalling pathway.Results Type II collagen (CII) was found to be enriched around MSU crystals in synovial fluid after cartilage injury. Imaging analysis revealed that CII regulated the morphology of single crystals and the alignment of crystal bows in the co-crystalline system, leading to greater phagocytosis and oxidative stress in macrophages. Furthermore, CII upregulated MSU-induced chemokine and proinflammatory cytokine expression in macrophages, thereby promoting the recruitment of leucocytes. Mechanistically, CII enhanced MSU-mediated inflammation by activating the integrin β1(ITGB1)-dependent TLR2/4-NF-κB signal pathway.Conclusion Our study demonstrates that the release of CII and protein-crystal adsorption modifies the crystal profile and promotes the early immune response in MSU-mediated inflammation. These findings open up a new path for understanding the relationship between cartilage injuries and the early immune response in gout flares.Data are available on reasonable request.