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Orderly arrayed deposit of urate crystals in gout suggest epitaxial formation
  1. ELISEO PASCUAL
  1. Rheumatology section, Hospital General Universitario de Alicante
  2. Petrology Unit, Facultad de Ciencias, Universidad de Alicante
  1. Dr E Pascual, Sección de Reumatología, Hospital General Universitario de Alicante, Maestro Alonso 109, 03010 Alicante, Spain.
  1. SALVADOR ORDÓÑEZ
  1. Rheumatology section, Hospital General Universitario de Alicante
  2. Petrology Unit, Facultad de Ciencias, Universidad de Alicante
  1. Dr E Pascual, Sección de Reumatología, Hospital General Universitario de Alicante, Maestro Alonso 109, 03010 Alicante, Spain.

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The mechanisms responsible for the initial deposit of monosodium urate (MSU) crystals in gouty joints remain obscure. We report on nine small fragments of tissue that showed an arranged deposit MSU crystals, which were obtained along with synovial fluid (SF) from asymptomatic gouty joints. Three of the fragments had chondrocytic islands, indicating their cartilaginous nature; MSU crystals were found in their depth, all oriented in the same direction and in two of them, a parallel fibrillar appearance of its matrix was apparent following the MSU crystals in the same direction as the fibres (fig 1A). Bundles of undulating parallel fibres—probably of cartilage collagen—detached from two of these fragments. The remaining fragments were composed by similar bundles of undulating parallel fibres without a cellular component, and may constitute remanents of fibrillating cartilage. In four of these fragments, individual crystals were deposited densely packed in transverse rows, following the undulations of the fibres, and always positioned alongside them (fig 1B). Finally, in two additional fragments fewer crystals were seen, always laying parallel to the fibres and following their undulations (fig 1C).

Figure 1

(A): Cartilage fragment; a chondrocyte in an island is seen. MSU crystals are placed in parallel, following the direction of the fibrillar matrix. Many of the crystals show dark against the bright birefringent matrix (under the microscope, crystals lying on the tissue and those MSU crystals freely floating in the synovial fluid had similar characteristics). Uncompensated polarised light, original magnification × 1000. (B): Fragment constituted by fibres with densely packed crystals deposited adjacently; the rows of crystals following the ups and downs of the undulations of the fibres are seen. (Under the microscope, crystals lying on the tissue and those MSU crystals freely floating in the synovial fluid had similar characteristics). Polarised light and first order red compensator original magnication × 1000. (C): One of the bundles of fibres containing only a few MSU crystals, which loosely follow the ups and downs of its undulations. Uncompensated polarised light original magnification × 1000.

All the SF samples in which the fragments were found contained abundant typical MSU crystals: strongly birefringent needle shaped, showing negative elongation when observed with compensated polarised light, and similar to those found on the tissue fragments. We have an interest in gout, and run a gout clinic where arthrocentesis of asymptomatic knee and first MTP joints is habitual. All the fragments were found in these SF samples (eight knee, one MTP) where, because of the small volume of fluid and scarce cellularity, any fragment desquamating into the joint cavity from surrounding tissues is likely to be recovered together with the SF. The first two findings were incidental; then samples of SF were scanned for fragments at 40 × with crossed polarised filters. All investigations were performed by one of the authors (EP) using an Olympus BH polarising microscope.

The orderly array of MSU crystals, and its close relation with the fibres adjacent cannot be casual. In fact, such an organised disposition of the crystals on tissue is a characteristic of epitaxial crystal formation, which physiologically occurs in biomineralisation, a process by which many living organisms control the formation of mineral crystals to add strength to some of their essential structural parts—such as bone, ossified tendons or mollusc shells.1-3 Our findings seem indicative that the same mechanism may be leading to the deposition of MSU crystals in the joint.

Epitaxial growth of crystals requires the existence of a specific support, which having stereochemical complementarity with the active face of the crystal, acts as a template for its nucleation by interacting stereo specifically with molecules in solution that incorporates the growing crystal. The combination formed by the support and the crystal nucleation centre is specific for each crystal, having been compared with the receptor sites for enzymes, genes or antibodies.3 4 Most important, epitaxial nucleation and growth occurs with a specific lowering of the required crystallisation energy; consequently, the support acts as a primer promoting the formation of crystals at lower concentrations of the solute, actively determining the sites at which the crystals form.5

The disposition of the MSU crystals tightly packed alongside fibres appreciated in four of the fragments seems indicative of primary epitaxial formation of the crystals on supports in—or related—to these fibres; in the other fragments the relation is looser but clear. The specificity of the support may determine that the crystal formed is MSU, and not a different uric acid salt, which would require a support with a different structure. The undulation of the fibres indicates that the fibres were probably free when the crystals formed. The relation between MSU crystals and the adjacent fibres is similar to that of apatite crystals and collagen fibres in the ossified turkey leg tendon—a model of epitaxial biomineralisation.6 7 A close relation between calcium pyrophosphate dihydrate crystals and collagen fibres8 may result from a similar mechanism of formation. Because of their large size and optical characteristics, MSU crystals may offer a rare opportunity for observing the orderly arrangement of the crystals on the support on which they have formed, by means of a simple optic microscope.

Acknowledgments

This study received partial support from fis grant 96/1212.

References

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