| Title: | Identification of an Osteochondral Erosion Process in Gout Driven by Fibrinogen-Integrin Activation and Local MSU Crystallization |
| Journal: | Advanced Science |
| Published: | 13 Jul 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42439437/ |
| DOI: | https://doi.org/10.1002/advs.76383 |
Publication 20296
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Abstract
Gout is characterized by monosodium urate (MSU) crystal deposition, recurrent inflammatory flares, and progressive cartilage erosion. However, the reasons for preferential MSU crystal formation at cartilage injury sites and the drivers of cartilage degradation remain unknown. Here, the dynamics of MSU crystal deposition in cartilage were investigated using stimulated Raman scattering microscopy combined with isotope labeling. MSU crystals preferentially accumulated at cartilage injury sites in a crystallization-frequency-dependent pattern, and multicycle MSU crystallization promoted deeper deposition in injured cartilage. Proteomics revealed local enrichment of the fibrinogen complex following cartilage injury. In vivo and in vitro validation experiments further showed that fibrinogen gamma chain (FGG) deposition co-localized with local MSU accumulation, accelerated MSU crystallization, and determined the site preference of deposition in a gout model. FGG and MSU deposition were further linked to integrin-related adhesion signaling and matrix-degrading programs. Cartilage injury, FGG deposition, and selective MSU crystallization together constitute a vicious cycle in gouty cartilage erosion, which can be interrupted by urokinase treatment or cartilage barrier restoration. In conclusion, cartilage injury promotes local fibrinogen deposition and deeper crystal invasion, thereby forming a self-amplifying loop that contributes to gout-associated cartilage erosion. This study also provides new biomarkers and therapeutic targets for gout management.</p>
8 Authors
- Hanlin Xu
- Simin Bi
- Zhechen Liu
- Xiaofeng Zhou
- Hengwei Qin
- Nicola Dalbeth
- Minbiao Ji
- Yinghui Hua
1 Application
| Application ID | Title |
|---|---|
| 742419 | Investigating the Interconnected Mechanisms of Gout, Cardiovascular Disease, and Osteoarthritis: Using Multi-Omics and Lifestyle Data for Risk Prediction and Therapeutic Target Identification |
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