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Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model
Polycronis P Akouris1,2, John A Chmiel1,2, Gerrit A Stuivenberg1,2
1Canadian Centre for Human Microbiome and Probiotics, London, ON, Canada.
Abstract:
Kidney stone disease affects nearly one in ten individuals and places a significant economic strain on global healthcare systems. Despite the high frequency of stones within the population, effective preventative strategies are lacking and disease prevalence continues to rise. Osteopontin (OPN) is a urinary protein that can inhibit the formation of renal calculi in vitro. However, the efficacy of OPN in vivo has yet to be determined. Using an established Drosophila melanogaster model of calcium oxalate urolithiasis, we demonstrated that a 16-residue synthetic OPN phosphopeptide effectively reduced stone burden in vivo. Oral supplementation with this peptide altered crystal morphology of calcium oxalate monohydrate (COM) in a similar manner to previous in vitro studies, and the presence of the OPN phosphopeptide during COM formation and adhesion significantly reduced crystal attachment to mammalian kidney cells. Altogether, this study is the first to show that an OPN phosphopeptide can directly mitigate calcium oxalate urolithiasis formation in vivo by modulating crystal morphology. These findings suggest that OPN supplementation is a promising therapeutic approach and may be clinically useful in the management of urolithiasis in humans.
Insights
A synthetic Osteopontin (OPN) phosphopeptide effectively reduced kidney stone formation in a fruit fly model. This peptide altered crystal structure, preventing stone buildup and attachment to kidney cells, suggesting a promising new therapy for urolithiasis.
Area of Science:
- Biochemistry
- Nephrology
- Molecular Biology
Background:
- Kidney stone disease is prevalent, costly, and lacks effective prevention.
- Osteopontin (OPN) inhibits kidney stone formation in vitro, but in vivo efficacy is unknown.
Purpose of the Study:
- To investigate the in vivo efficacy of a synthetic OPN phosphopeptide in preventing calcium oxalate urolithiasis.
- To determine if OPN peptide can modulate crystal morphology and reduce stone burden.
Main Methods:
- Utilized a Drosophila melanogaster model of calcium oxalate urolithiasis.
- Administered a synthetic 16-residue OPN phosphopeptide orally.
- Analyzed crystal morphology and attachment to mammalian kidney cells.
Main Results:
- The OPN phosphopeptide significantly reduced kidney stone burden in vivo.
- Oral peptide supplementation altered calcium oxalate monohydrate (COM) crystal morphology.
- The peptide reduced COM crystal attachment to kidney cells.
Conclusions:
- This is the first study demonstrating in vivo efficacy of an OPN phosphopeptide against calcium oxalate urolithiasis.
- OPN phosphopeptide mitigates urolithiasis by modulating crystal morphology and reducing crystal adhesion.
- OPN supplementation represents a promising therapeutic strategy for human urolithiasis.
