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Abstract: FR-PO522

Matrix Protein Differences Between Various Stone Types

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Author

  • Wesson, Jeffrey, VA Medical Center, Milwaukee, Wisconsin, United States
Background

Enrichment of highly anionic and highly cationic proteins was observed in calcium oxalate monohydrate (COM) stone matrix, but ittle is known about protein distributions other stone types. In this study, stone matrix proteins have been quantitatively identified in other stone types, including uric acid (UA), calcium oxalate dihydrate (COD), and basic calcium phosphate (BCP) using a previously reported method.

Methods

Stone matrix proteins were isolated from 11 COM stones (>60% COM content), 6 UA stone samples (>95% UA content), 6 COD stones (>50% COD content), and 5 BCP stones (>50% BCP content) by dissolution in sequential washes with an EDTA/SDS solution at pH=8 with dithiothreitol added. The solubilized proteins from each stone were concentrated and desalted by ultradiafiltration. Proteomic analysis was performed at the Medical College of Wisconsin Innovation Center using non-labelled, quantitative mass spectrometry methods and reported as spectral counts (SC), including only proteins with 2 or more peptide matches at >85% confidence, after removing keratin and redundant proteins.

Results

All samples contained >1,000 SC, but the total protein signal was slightly smaller in COM compared to other stone types. More than 400 unique proteins were identified in each stone type, but a smaller subset were both frequent and abundant in each stone type: 69 proteins in ≥7 of 11 COM stones (89% SC); 126 proteins in ≥4 of 6 COD stones (85% SC); 108 proteins in ≥3 of 5 BCP stones (92% SC), and 51 proteins in ≥4 of 6 UA stones (67% SC). Most abundant proteins were common between the different stone types, and all stone types were enriched in strongly cationic proteins. Calcium containing stones were also enriched in strongly anionic proteins, more prominently in COM compared to COD or BCP. UA stones exhibited a markedly different proteome compared to calcium stones, with fewer nuclear proteins and more inflammatory components.

Conclusion

Stone matrix proteins exhibit distinctly different patterns in each stone type, implying that unique crystal interactions with proteins and/or cell surfaces control their pathogenesis. The prominence of strongly anionic proteins in calcium stones, particularly in COM suggests that polyanion-polycation aggregation is a plausible mechanism for COM stone formation. Conversely, UA stone formation may be more dependent on inflammatory pathways, but the link to crystal aggregation is unkown.

Funding

  • Private Foundation Support