Factors influencing the crystallization of monosodium urate: a systematic literature review

Abstract

BackgroundGout is a chronic disease of monosodium urate (MSU) crystal deposition. Although hyperuricaemia is the central risk factor for development of gout, not all people with hyperuricaemia have subclinical MSU crystal deposition or indeed, symptomatic disease. The aim of this systematic literature review was to identify factors that contribute to MSU crystallization.MethodsA search was conducted of the electronic databases PubMed, Science Direct and Scopus. Articles were included if they contained original data related to MSU crystallization. The methods and results were summarized and categorized into articles describing at least one of the three key steps in MSU crystallization (reduced urate solubility, nucleation and growth).ResultsA total of 2175 articles were initially identified in our systematic search with 35 of these articles included in the final analysis. Elevated urate concentration was identified as a central factor driving all three stages of MSU crystallization. Factors that were found to consistently reduce urate solubility were reduced temperatures, pH 7–9 and various ions including sodium ions. Connective tissue factors including bovine cartilage homogenates and healthy human synovial fluid and serum all enhanced urate solubility. MSU nucleation was found to be increased by a number of factors, including sodium ions, uric acid binding antibodies, and synovial fluid or serum from patients with gout. Other than elevated urate concentrations, no other specific factors were identified as promoters of MSU crystal growth.ConclusionsIncreased urate concentration is the key factor required at each stage of MSU crystallization. Different proteins and factors within connective tissues may promote MSU crystallization and may be important for determining the sites at which MSU crystallization occurs in the presence of elevated urate concentrations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-015-0762-4) contains supplementary material, which is available to authorized users.

Persistence of Monosodium Urate Crystals and Calcium Pyrophosphate Crystals in Synovial Fluid Samples After Two Weeks of Storage at 4 °C and −20 °C: A Longitudinal Analysis

“…Our findings align with previous reports on the persistence of MSU crystals in synovial fluid over two to eight weeks at room temperature or lower, regardless of the preservative used [9,11]. The stability of MSU crystals can be explained by their temperature-dependent solubility, as urate crystals become less soluble at lower temperatures [15]. Additionally, the use of EDTA-coated containers prevents white blood cell lysis, which may further help preserve neutrophils containing phagocytosed crystals [16].…”

Persistence of Monosodium Urate Crystals and Calcium Pyrophosphate Crystals in Synovial Fluid Samples After Two Weeks of Storage at 4 °C and −20 °C: A Longitudinal Analysis

“…Our findings align with previous reports on the persistence of MSU crystals in synovial fluid over two to eight weeks at room temperature or lower, regardless of the preservative used [9,11]. The stability of MSU crystals can be explained by their temperature-dependent solubility, as urate crystals become less soluble at lower temperatures [15]. Additionally, the use of EDTA-coated containers prevents white blood cell lysis, which may further help preserve neutrophils containing phagocytosed crystals [16].…”

Osteoarthritis synovium as a nidus for monosodium urate crystal deposition inducing severe gout studied by label‐free stimulated Raman scattering combined with synovial organoids

“…Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation. 31 , 40 , 41 Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids. A number of factors have been identified to be correlated with MSU crystal phagocytosis, including ECM protein, cartilage particles, and inflammatory mediators generated during OA.…”

“…The pathological alternations in the OA synovium may be related to MSU crystal deposition and deformation. Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation 31,40,41 . Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids.…”

Hyperuricemia is associated with intermittent hand joint pain in a cross sectional study of elderly females: The AGES-Reykjavik Study

“…A number of external factors such as usage, microtrauma and temperature as well as dehydration have been implicated in inducing gouty episodes[24]. Increased urate concentration appears to be the universal key factor in igniting the inflammatory response although other proteins and factors may act as promoters [25]. Interpreting the current findings, it appears that these metabolic and external circumstances may be present in the hand joints of elderly females.…”

Persistence of Monosodium Urate Crystals and Calcium Pyrophosphate Crystals in Synovial Fluid Samples After Two Weeks of Storage at 4 °C and −20 °C: A Longitudinal Analysis

“…Our findings align with previous reports on the persistence of MSU crystals in synovial fluid over two to eight weeks at room temperature or lower, regardless of the preservative used [9,11]. The stability of MSU crystals can be explained by their temperature-dependent solubility, as urate crystals become less soluble at lower temperatures [15]. Additionally, the use of EDTA-coated containers prevents white blood cell lysis, which may further help preserve neutrophils containing phagocytosed crystals [16].…”

Osteoarthritis synovium as a nidus for monosodium urate crystal deposition inducing severe gout studied by label‐free stimulated Raman scattering combined with synovial organoids

“…Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation. 31 , 40 , 41 Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids. A number of factors have been identified to be correlated with MSU crystal phagocytosis, including ECM protein, cartilage particles, and inflammatory mediators generated during OA.…”

“…The pathological alternations in the OA synovium may be related to MSU crystal deposition and deformation. Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation 31,40,41 . Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids.…”

Hyperuricemia is associated with intermittent hand joint pain in a cross sectional study of elderly females: The AGES-Reykjavik Study

“…A number of external factors such as usage, microtrauma and temperature as well as dehydration have been implicated in inducing gouty episodes[24]. Increased urate concentration appears to be the universal key factor in igniting the inflammatory response although other proteins and factors may act as promoters [25]. Interpreting the current findings, it appears that these metabolic and external circumstances may be present in the hand joints of elderly females.…”

Persistence of Monosodium Urate Crystals and Calcium Pyrophosphate Crystals in Synovial Fluid Samples After Two Weeks of Storage at 4 °C and −20 °C: A Longitudinal Analysis

“…Our findings align with previous reports on the persistence of MSU crystals in synovial fluid over two to eight weeks at room temperature or lower, regardless of the preservative used [9,11]. The stability of MSU crystals can be explained by their temperature-dependent solubility, as urate crystals become less soluble at lower temperatures [15]. Additionally, the use of EDTA-coated containers prevents white blood cell lysis, which may further help preserve neutrophils containing phagocytosed crystals [16].…”

Osteoarthritis synovium as a nidus for monosodium urate crystal deposition inducing severe gout studied by label‐free stimulated Raman scattering combined with synovial organoids

“…Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation. 31 , 40 , 41 Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids. A number of factors have been identified to be correlated with MSU crystal phagocytosis, including ECM protein, cartilage particles, and inflammatory mediators generated during OA.…”

“…The pathological alternations in the OA synovium may be related to MSU crystal deposition and deformation. Fibrotic OA synoviocytes may overproduce ECM debris, such as fibronectin and type I collagen, predisposing them to MSU crystal formation 31,40,41 . Furthermore, this study demonstrated that OA synovial organoids were more capable of MSU phagocytosis than normal synovial organoids.…”

Hyperuricemia is associated with intermittent hand joint pain in a cross sectional study of elderly females: The AGES-Reykjavik Study

“…A number of external factors such as usage, microtrauma and temperature as well as dehydration have been implicated in inducing gouty episodes[24]. Increased urate concentration appears to be the universal key factor in igniting the inflammatory response although other proteins and factors may act as promoters [25]. Interpreting the current findings, it appears that these metabolic and external circumstances may be present in the hand joints of elderly females.…”