Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment
© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:82 |
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| Enthalten in: |
Annals of the rheumatic diseases - 82(2023), 3 vom: 01. März, Seite 416-427 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, HanLin [VerfasserIn] |
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| Links: |
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| Themen: |
268B43MJ25 |
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| Anmerkungen: |
Date Completed 14.02.2023 Date Revised 27.02.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1136/ard-2022-222764 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346258995 |
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| 245 | 1 | 0 | |a Type II collagen facilitates gouty arthritis by regulating MSU crystallisation and inflammatory cell recruitment |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 14.02.2023 | ||
| 500 | |a Date Revised 27.02.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a chemokines | |
| 650 | 4 | |a crystal arthropathies | |
| 650 | 4 | |a gout | |
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| 700 | 1 | |a Zhang, Bohan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yaxin |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Fengzhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Wenjuan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ziyi |e verfasserin |4 aut | |
| 700 | 1 | |a Cao, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Xiaoxia |e verfasserin |4 aut | |
| 700 | 1 | |a Xue, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a He, Rui |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, MinBiao |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, YingHui |e verfasserin |4 aut | |
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