Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model

Polycronis P Akouris; John A Chmiel; Gerrit A Stuivenberg; Wongsakorn Kiattiburut; Jennifer Bjazevic; Hassan Razvi; Bernd Grohe; Harvey A Goldberg; Jeremy P Burton; Kait F Al

doi:10.1007/s00240-022-01395-2

Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model

Urolithiasis. 2022 Dec 22;51(1):19. doi: 10.1007/s00240-022-01395-2.

Authors

Polycronis P Akouris^{1

2}, John A Chmiel^{1

2}, Gerrit A Stuivenberg^{1

2}, Wongsakorn Kiattiburut^{1

2}, Jennifer Bjazevic³, Hassan Razvi³, Bernd Grohe¹, Harvey A Goldberg^{4

5}, Jeremy P Burton^{1

2

3}, Kait F Al^{6

7}

Affiliations

¹ Canadian Centre for Human Microbiome and Probiotics, London, ON, Canada.
² Department of Microbiology and Immunology, Western University, London, ON, Canada.
³ Division of Urology, Department of Surgery, Western University, London, ON, Canada.
⁴ Department of Biochemistry, Western University, London, ON, Canada.
⁵ School of Dentistry, Western University, London, ON, Canada.
⁶ Canadian Centre for Human Microbiome and Probiotics, London, ON, Canada. kal@uwo.ca.
⁷ Department of Microbiology and Immunology, Western University, London, ON, Canada. kal@uwo.ca.

PMID: 36547746
DOI: 10.1007/s00240-022-01395-2

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.

Keywords: Calcium oxalate; Crystal formation inhibitor; Drosophila melanogaster; Osteopontin; Urolithiasis.

MeSH terms

Animals
Calcium Oxalate* / metabolism
Disease Models, Animal
Drosophila melanogaster
Kidney Calculi* / drug therapy
Kidney Calculi* / metabolism
Osteopontin* / pharmacology
Osteopontin* / therapeutic use
Phosphopeptides* / pharmacology
Phosphopeptides* / therapeutic use

Substances

Calcium Oxalate
Osteopontin
Phosphopeptides