title: Osteopontin is a critical inhibitor of calcium oxalate crystal formation and retention in renal tubules.
abstract: Calcium nephrolithiasis is the most common form of renal stone disease, with calcium oxalate (CaOx) being the predominant constituent of renal stones. Current in vitro evidence implicates osteopontin (OPN) as one of several macromolecular inhibitors of urinary crystallization with potentially important actions at several stages of CaOx crystal formation and retention. To determine the importance of OPN in vivo, hyperoxaluria was induced in mice targeted for the deletion of the OPN gene together with wild-type control mice. Both groups were given 1% ethylene glycol, an oxalate precursor, in their drinking water for up to 4 wk. At 4 wk, OPN-deficient mice demonstrated significant intratubular deposits of CaOx crystals, whereas wild-type mice were completely unaffected. Retained crystals in tissue sections were positively identified as CaOx monohydrate by both polarized optical microscopy and x-ray powder diffraction analysis. Furthermore, hyperoxaluria in the OPN wild-type mice was associated with a significant 2- to 4-fold upregulation of renal OPN expression by immunocytochemistry, lending further support to a renoprotective role for OPN. These data indicate that OPN plays a critical renoprotective role in vivo as an inhibitor of CaOx crystal formation and retention in renal tubules.
authors.affiliation: Department of Veterans Affairs Medical Center and Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Wesson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Marrilda
authors.initials: M
authors.lastname: Mazzali
authors.forename: Anne M
authors.initials: AM
authors.lastname: Beshensky
authors.forename: Susan
authors.initials: S
authors.lastname: Stietz
authors.forename: Ceci
authors.initials: C
authors.lastname: Giachelli
authors.forename: Lucy
authors.initials: L
authors.lastname: Liaw
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: William G
authors.initials: WG
authors.lastname: Couser
authors.forename: Jack G
authors.initials: JG
authors.lastname: Kleinman
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hughes
mesh_terms: D000818:Animals; D017209:Apoptosis; D002129:Calcium Oxalate / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism / Q000652:urine; D002455:Cell Division; D003460:Crystallization; D006959:Hyperoxaluria / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin; D002129:Calcium Oxalate