Evidence map›Paper›PMID 42390698›Full record

ArticleClinical rheumatology2026

Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis.

Zhijun Geng, Di Wu, Yajing Hou, Lulu Kang, Xiaofeng Zhang, Zian Feng, Jinghan Song, Danning Chen, Tianxun Zhang, Lin Xu and 2 more

Abstract read
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In one paragraph

Article in Clinical rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Zhijun GengState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Di WuState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Yajing HouState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Lulu KangState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Xiaofeng ZhangState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Zian FengState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Jinghan SongState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Danning ChenState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Tianxun ZhangState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China.
Lin XuSchool of Medical Technology, Xinxiang Medical University, Xinxiang, 453003, Henan, China.
Xiang GaoState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China. gaoxiang@nju.edu.cn.
Zhaoyu LinState Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animals for Disease Study, Jiangsu Key Laboratory of Molecular Medicine, Model Animal Research Center, National Resource Center for Mutant Mice of China, Nanjing Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing, 210061, China. linzy@nju.edu.cn.ORCID http://orcid.org/0000-0003-2095-7814

Funding

Fundamental Research Funds for the Central Universities 021414380533Ministry of Science and Technology of China 2021YFF0702100National Natural Science Foundation of China 32471238Noncommunicable Chronic Diseases-National Science and Technology Major Project 2025ZD0550102The Open Project of Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases YZ2024Z01The Open Project of Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases YZ2024Z02The Open Project of Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases YZ2025A01
6 · The paper itself

Abstract

objectivesMacrophage lytic death induced by monosodium urate (MSU) crystals is critical for gout initiation, but its mechanisms remain unclear. MSU activates the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome and canonical pyroptosis; this study aimed to define the cell death pathways mediating MSU crystal-induced macrophage death.

methodWe assessed canonical inflammasome activation (apoptosis-associated speck-like protein containing a CARD (ASC) speck, caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β)) in macrophages. Using genetically deficient macrophages (GSDMD⁻/⁻, NLRP3⁻/⁻, and caspase-1⁻/⁻) and pharmacological inhibitors, we evaluated lytic death and in vivo inflammation. We also checked caspase-3/gasdermin E (GSDME) pyroptosis, necroptosis, ferroptosis, and ROS.

resultsMSU crystals strongly activated canonical inflammasome signaling, as evidenced by ASC speck formation, caspase-1 activation, GSDMD cleavage, and IL-1β secretion. However, genetic ablation of GSDMD, NLRP3, or caspase-1 did not prevent MSU crystal-induced macrophage lytic death. Similarly, deficiency of GSDMD or NLRP3 did not alleviate inflammation in mouse models of gout. MSU crystals did not trigger caspase-3/GSDME-dependent pyroptosis. While necroptosis contributed to cell death when canonical pyroptosis was blocked, inhibiting necroptosis alone was insufficient to abolish MSU crystal-induced lysis. Combined inhibition of caspases and necroptosis moderately, but significantly, reduced lytic death, whereas additional blockade of ferroptosis or reactive oxygen species (ROS) did not further enhance this protective effect.

conclusionsMSU crystal-induced macrophage lytic death represent a complex cell death program that is not exclusively dependent on canonical pyroptosis or necroptosis. These findings uncover a previously unrecognized mechanism of MSU-mediated cytotoxicity and offer novel insights into the molecular pathogenesis of gout. Key Points • Monosodium urate (MSU) crystals trigger macrophage lytic cell death via synergistic canonical pyroptosis and necroptosis, instead of a single cell death pathway. GSDME-dependent pyroptosis, ferroptosis, and ROS are not pivotal drivers of this process. • Combined inhibition of canonical pyroptosis and necroptosis partially reduces MSU crystal-induced macrophage death.

Indexed as

GoutMacrophagesNecroptosisPyroptosisUric AcidAnimalsCaspase 1GasderminsInflammasomesIntracellular Signaling Peptides and ProteinsMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPhosphate-Binding ProteinsReactive Oxygen SpeciesCaspase 1GasderminsGsdmd protein, mouseInflammasomesIntracellular Signaling Peptides and ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePhosphate-Binding ProteinsReactive Oxygen SpeciesUric AcidGoutLytic cell deathMacrophageMSU crystalsNecroptosisNLRP3 inflammasomePyroptosis

Identifiers

PMID42390698

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.