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01-12-2023 | Urolithiasis | Research

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

Authors: 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

Published in: Urolithiasis | Issue 1/2023

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.

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Sorokin I, Mamoulakis C, Miyazawa K et al (2017) Epidemiology of stone disease across the world. World J Urol 35:1301–1320. https://doi.org/10.1007/s00345-017-2008-6CrossRefPubMed

Khan SR, Pearle MS, Robertson WG et al (2016) Kidney stones. Nat Rev Dis Primers 2:16008. https://doi.org/10.1038/nrdp.2016.8CrossRefPubMedPubMedCentral

Thongprayoon C, Krambeck AE, Rule AD (2020) Determining the true burden of kidney stone disease. Nat Rev Nephrol 16:736–746. https://doi.org/10.1038/s41581-020-0320-7CrossRefPubMed

Paterson R, Fernandez A, Razvi H, Sutton R (2010) Evaluation and medical management of the kidney stone patient. Can Urol Assoc J 4:375–379. https://doi.org/10.5489/cuaj.10166CrossRefPubMedPubMedCentral

Worcester EM, Coe FL (2010) Calcium kidney stones. N Engl J Med 363:954–963. https://doi.org/10.1056/NEJMcp1001011CrossRefPubMedPubMedCentral

Khan SR, Kok DJ (2004) Modulators of urinary stone formation. Front Biosci Landmark 9:1450–1482. https://doi.org/10.2741/1347CrossRef

Chmiel JA, Stuivenberg GA, Alathel A et al (2022) High-throughput in vitro gel-based plate assay to screen for calcium oxalate stone inhibitors. UIN 106:616–622. https://doi.org/10.1159/000519842CrossRef

Grohe B, Chan BPH, Sørensen ES et al (2011) Cooperation of phosphates and carboxylates controls calcium oxalate crystallization in ultrafiltered urine. Urol Res 39:327–338. https://doi.org/10.1007/s00240-010-0360-8CrossRefPubMed

Zarse CA, Hameed TA, Jackson ME et al (2007) CT visible internal stone structure, but not Hounsfield unit value, of calcium oxalate monohydrate (COM) calculi predicts lithotripsy fragility in vitro. Urol Res 35:201–206. https://doi.org/10.1007/s00240-007-0104-6CrossRefPubMedPubMedCentral

10.

Majdalany SE, Levin BA, Ghani KR (2021) The efficiency of Moses technology holmium laser for treating renal stones during flexible ureteroscopy: relationship between stone volume, time, and energy. J Endourol 35:S-14. https://doi.org/10.1089/end.2021.0592CrossRef

11.

Taller A, Grohe B, Rogers KA et al (2007) Specific adsorption of osteopontin and synthetic polypeptides to calcium oxalate monohydrate crystals. Biophys J 93:1768–1777. https://doi.org/10.1529/biophysj.106.101881CrossRefPubMedPubMedCentral

12.

Hunter GK, Kyle CL, Goldberg HA (1994) Modulation of crystal formation by bone phosphoproteins: structural specificity of the osteopontin-mediated inhibition of hydroxyapatite formation. Biochem J 300:723–728. https://doi.org/10.1042/bj3000723CrossRefPubMedPubMedCentral

13.

Wada T, McKee MD, Steitz S, Giachelli CM (1999) Calcification of vascular smooth muscle cell cultures. Circ Res 84:166–178. https://doi.org/10.1161/01.RES.84.2.166CrossRefPubMed

14.

Sodek J, Ganss B, McKee MD (2000) Osteopontin. Crit Rev Oral Biol Med 11:279–303. https://doi.org/10.1177/10454411000110030101CrossRefPubMed

15.

Hunter GK, O’Young J, Grohe B et al (2010) The flexible polyelectrolyte hypothesis of protein−biomineral interaction. Langmuir 26:18639–18646. https://doi.org/10.1021/la100401rCrossRefPubMed

16.

Hoyer JR, Asplin JR, Otvos L (2001) Phosphorylated osteopontin peptides suppress crystallization by inhibiting the growth of calcium oxalate crystals. Kidney Int 60:77–82. https://doi.org/10.1046/j.1523-1755.2001.00772.xCrossRefPubMed

17.

Wesson JA, Johnson RJ, Mazzali M et al (2003) Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules. JASN 14:139–147. https://doi.org/10.1097/01.ASN.0000040593.93815.9DCrossRefPubMed

18.

Wang L, Zhang W, Qiu SR et al (2006) Inhibition of calcium oxalate monohydrate crystallization by the combination of citrate and osteopontin. J Cryst Growth 291:160–165. https://doi.org/10.1016/j.jcrysgro.2006.02.032CrossRef

19.

Grohe B, O’Young J, Ionescu DA et al (2007) Control of calcium oxalate crystal growth by face-specific adsorption of an osteopontin phosphopeptide. J Am Chem Soc 129:14946–14951. https://doi.org/10.1021/ja0745613CrossRefPubMed

20.

Hunter GK, Grohe B, Jeffrey S et al (2009) Role of phosphate groups in inhibition of calcium oxalate crystal growth by osteopontin. CTO 189:44–50. https://doi.org/10.1159/000151430CrossRefPubMed

21.

Langdon A, Wignall GR, Rogers K et al (2009) Kinetics of calcium oxalate crystal growth in the presence of osteopontin isoforms: an analysis by scanning confocal interference microcopy. Calcif Tissue Int 84:240–248. https://doi.org/10.1007/s00223-008-9215-5CrossRefPubMed

22.

Langdon A, Grohe B (2016) The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones. Colloids Surf B Biointerfaces 146:296–306. https://doi.org/10.1016/j.colsurfb.2016.06.030CrossRefPubMed

23.

Gleberzon JS, Liao Y, Mittler S et al (2019) Incorporation of osteopontin peptide into kidney stone-related calcium oxalate monohydrate crystals: a quantitative study. Urolithiasis 47:425–440. https://doi.org/10.1007/s00240-018-01105-xCrossRefPubMed

24.

Ibis F, Yu TW, Penha FM et al (2021) Nucleation kinetics of calcium oxalate monohydrate as a function of pH, magnesium, and osteopontin concentration quantified with droplet microfluidics. Biomicrofluidics 15:064103. https://doi.org/10.1063/5.0063714CrossRefPubMedPubMedCentral

25.

Ja WW, Carvalho GB, Mak EM et al (2007) Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci 104:8253–8256. https://doi.org/10.1073/pnas.0702726104CrossRefPubMedPubMedCentral

26.

Al KF, Daisley BA, Chanyi RM et al (2020) Oxalate-degrading Bacillus subtilis mitigates urolithiasis in a Drosophila melanogaster model. mSphere 5:e00498-e520. https://doi.org/10.1128/mSphere.00498-20CrossRefPubMedPubMedCentral

27.

Abramoff MD, Magalhães PJ, Ram SJ (2004) Image processing with ImageJ. Biophotonics Int 11:36–42

28.

Griffith DP, Musher DM, Itin C (1976) Urease. The primary cause of infection-induced urinary stones. Invest Urol 13:346–350PubMed

29.

Grohe B, Rogers KA, Goldberg HA, Hunter GK (2006) Crystallization kinetics of calcium oxalate hydrates studied by scanning confocal interference microscopy. J Cryst Growth 295:148–157. https://doi.org/10.1016/j.jcrysgro.2006.07.029CrossRef

30.

O’Young J, Chirico S, Tarhuni NA et al (2009) Phosphorylation of osteopontin peptides mediates adsorption to and incorporation into calcium oxalate crystals. CTO 189:51–55. https://doi.org/10.1159/000151724CrossRefPubMed

31.

Chen Y-H, Liu H-P, Chen H-Y et al (2011) Ethylene glycol induces calcium oxalate crystal deposition in Malpighian tubules: a Drosophila model for nephrolithiasis/urolithiasis. Kidney Int 80:369–377. https://doi.org/10.1038/ki.2011.80CrossRefPubMed

32.

Miller J, Chi T, Kapahi P et al (2013) Drosophila melanogaster as an emerging translational model of human nephrolithiasis. J Urol. https://doi.org/10.1016/j.juro.2013.03.010.10.1016/j.juro.2013.03.010CrossRefPubMedPubMedCentral

33.

Dow JAT, Romero MF (2010) Drosophila provides rapid modeling of renal development, function, and disease. Am J Physiol Renal Physiol 299:F1237–F1244. https://doi.org/10.1152/ajprenal.00521.2010CrossRefPubMedPubMedCentral

34.

Wang J, Kean L, Yang J et al (2004) Function-informed transcriptome analysis of Drosophila renal tubule. Genome Biol 5:R69. https://doi.org/10.1186/gb-2004-5-9-r69CrossRefPubMedPubMedCentral

35.

Yagisawa T, Chandhoke PS, Fan J, Lucia S (1998) Renal osteopontin expression in experimental urolithiasis. J Endourol 12:171–176. https://doi.org/10.1089/end.1998.12.171CrossRefPubMed

36.

Kleinman JG, Beshensky A, Worcester EM, Brown D (1995) Expression of osteopontin, a urinary inhibitor of stone mineral crystal growth, in rat kidney. Kidney Int 47:1585–1596. https://doi.org/10.1038/ki.1995.222CrossRefPubMed

37.

Yamate T, Tsuji H, Amasaki N et al (2000) Analysis of osteopontin DNA in patients with urolithiasis. Urol Res 28:159–166. https://doi.org/10.1007/s002400000112CrossRefPubMed

38.

Li X, Liu K, Pan Y et al (2015) Roles of osteopontin gene polymorphism (rs1126616), osteopontin levels in urine and serum, and the risk of urolithiasis: a meta-analysis. Biomed Res Int 2015:e315043. https://doi.org/10.1155/2015/315043CrossRef

39.

Liu C-C, Huang S-P, Tsai L-Y et al (2010) The impact of osteopontin promoter polymorphisms on the risk of calcium urolithiasis. Clin Chim Acta 411:739–743. https://doi.org/10.1016/j.cca.2010.02.007CrossRefPubMed

40.

Khan SR (1995) Calcium oxalate crystal interaction with renal tubular epithelium, mechanism of crystal adhesion and its impact on stone development. Urol Res 23:71–79. https://doi.org/10.1007/BF00307936CrossRefPubMed

41.

Lieske JC, Leonard R, Swift H, Toback FG (1996) Adhesion of calcium oxalate monohydrate crystals to anionic sites on the surface of renal epithelial cells. Am J Physiol 270:F192-199. https://doi.org/10.1152/ajprenal.1996.270.1.F192CrossRefPubMed

42.

Lieske JC, Norris R, Toback FG (1997) Adhesion of hydroxyapatite crystals to anionic sites on the surface of renal epithelial cells. Am J Physiol 273:F224-233. https://doi.org/10.1152/ajprenal.1997.273.2.F224CrossRefPubMed

43.

Lieske JC, Leonard R, Toback FG (1995) Adhesion of calcium oxalate monohydrate crystals to renal epithelial cells is inhibited by specific anions. Am J Physiol 268:F604-612. https://doi.org/10.1152/ajprenal.1995.268.4.F604CrossRefPubMed

44.

Kleinman JG, Alatalo LJ, Beshensky AM, Wesson JA (2008) Acidic polyanion poly(acrylic acid) prevents calcium oxalate crystal deposition. Kidney Int 74:919–924. https://doi.org/10.1038/ki.2008.253CrossRefPubMedPubMedCentral

45.

Sridharan B, Jagannathan V, Rajesh NG, Viswanathan P (2022) Combined effect of polyacrylic acid and vitamin E in preventing calcium oxalate crystal deposition in the kidneys of experimental hyperoxaluric rats. Cell Biochem Funct 40:152–163. https://doi.org/10.1002/cbf.3683CrossRef

46.

Coe FL, Evan AP, Worcester EM, Lingeman JE (2010) Three pathways for human kidney stone formation. Urol Res 38:147–160. https://doi.org/10.1007/s00240-010-0271-8CrossRefPubMedPubMedCentral

Title: Osteopontin phosphopeptide mitigates calcium oxalate stone formation in a Drosophila melanogaster model
Authors: 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
Publication date: 01-12-2023
Publisher: Springer Berlin Heidelberg
Keyword: Urolithiasis
Published in: Urolithiasis / Issue 1/2023
Print ISSN: 2194-7228
Electronic ISSN: 2194-7236
DOI: https://doi.org/10.1007/s00240-022-01395-2

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

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