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Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment
  1. HanLin Xu1,
  2. Bohan Zhang2,
  3. Yaxin Chen2,
  4. Fengzhen Zeng3,
  5. Wenjuan Wang1,
  6. Ziyi Chen1,
  7. Ling Cao4,
  8. Jun Shi3,
  9. Jun Chen1,
  10. Xiaoxia Zhu4,
  11. Yu Xue4,
  12. Rui He5,6,
  13. MinBiao Ji2,
  14. YingHui Hua1
  1. 1Department of Sports Medicine, Huashan Hospital,Fudan University, Shanghai, China
  2. 2State Key Laboratory of Surface Physics and Department of Physics, Human Phenome Institute, Academy for Engineering and Technology, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Yiwu Research Institute, Fudan University, Shanghai, China
  3. 3School of Communication and Information Engineering, Shanghai University, Shanghai, China
  4. 4Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China
  5. 5Department of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China
  6. 6National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
  1. Correspondence to Prof YingHui Hua, Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China; hua_cosm{at}aliyun.com; Prof MinBiao Ji; minbiaoj{at}fudan.edu.cn; Prof Rui He; ruihe{at}fudan.edu.cn

Abstract

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.

  • gout
  • crystal arthropathies
  • chemokines

Data availability statement

Data are available on reasonable request.

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Data availability statement

Data are available on reasonable request.

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Footnotes

  • Handling editor Josef S Smolen

  • HX and BZ contributed equally.

  • Correction notice This article has been corrected since it published Online First. The author details for MinBiao Ji have been updated.

  • Contributors YH is responsible for the overall content as guarantor. YH, MJ and RH designed and directed the study. HX, BZ, WW, ZC and LC performed molecular biology and optical experiments. BZ and YC performed stimulated Raman scattering microscopy experiments and data collection. FZ and JS performed programming and image analysis. XZ, YX and JC carried out the design of the experimentals and analysis of the results. RH, MJ, HX and BZ wrote the manuscript with contributions from all the authors.

  • Funding This work was supported by the National Key R&D Programme of China (grant numbers 2020YFA0803800, 2021YFF0502900); National Natural Science Foundation of China (61975033, 32170899); and Shanghai Municipal Science and Technology Major Project No. 2018SHZDZX01 and ZJLab.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.