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The Crystallization of Monosodium Urate

  • CRYSTAL ARTHRITIS (MH PILLINGER, SECTION EDITOR)
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Abstract

Gout is a common crystal-induced arthritis, in which monosodium urate (MSU) crystals precipitate within joints and soft tissues and elicit an inflammatory response. The causes of elevated serum urate and the inflammatory pathways activated by MSU crystals have been well studied, but less is known about the processes leading to crystal formation and growth. Uric acid, the final product of purine metabolism, is a weak acid that circulates as the deprotonated urate anion under physiologic conditions, and combines with sodium ions to form MSU. MSU crystals are known to have a triclinic structure, in which stacked sheets of purine rings form the needle-shaped crystals that are observed microscopically. Exposed, charged crystal surfaces are thought to allow for interaction with phospholipid membranes and serum factors, playing a role in the crystal-mediated inflammatory response. While hyperuricemia is a clear risk factor for gout, local factors have been hypothesized to play a role in crystal formation, such as temperature, pH, mechanical stress, cartilage components, and other synovial and serum factors. Interestingly, several studies suggest that MSU crystals may drive the generation of crystal-specific antibodies that facilitate future MSU crystallization. Here, we review MSU crystal biology, including a discussion of crystal structure, effector function, and factors thought to play a role in crystal formation. We also briefly compare MSU biology to that of uric acid stones causing nephrolithasis, and consider the potential treatment implications of MSU crystal biology.

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Acknowledgments

The authors thank David Goldfarb and Michael Pillinger for helpful input with the text, and Michael Ward for reviewing the accuracy of the figures.

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Conflict of Interest

This work was supported in part by grants from the Arthritis Foundation and New York Academy of Medicine (to Daria B. Crittenden), and by grant UL1 TR000038 from the National Center for Advancing Translational Sciences, National Institutes of Health.

Miguel A. Martillo, Lama Nazzal, and Daria B. Crittenden declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Divisions of Rheumatology, Department of Medicine, NYU School of Medicine, New York, USA

    Miguel A. Martillo & Daria B. Crittenden

  2. Divisions of Nephrology, Department of Medicine, NYU School of Medicine, New York, USA

    Lama Nazzal

  3. Sections of Rheumatology, Department of Medicine, New York Harbor Health VA Care System, New York Campus, New York, USA

    Miguel A. Martillo & Daria B. Crittenden

  4. Sections of Nephrology, Department of Medicine, New York Harbor Health VA Care System, New York Campus, New York, USA

    Lama Nazzal

  5. Department of Rheumatology, NYU Hospital for Joint Diseases, 301 East 17th Street, Suite 1410, New York, NY, 10003, USA

    Daria B. Crittenden

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  1. Miguel A. Martillo
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  2. Lama Nazzal
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Correspondence to Daria B. Crittenden.

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This article is part of the Topical Collection on Crystal Arthritis

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Martillo, M.A., Nazzal, L. & Crittenden, D.B. The Crystallization of Monosodium Urate. Curr Rheumatol Rep 16, 400 (2014). https://doi.org/10.1007/s11926-013-0400-9

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