Osteopontin and Calcium Stone Formation

Kleinman, Joel C.; Wesson, Jeffrey A.; Hughes, Jeremy

doi:10.1159/000080263

Cited by 69 publications

(52 citation statements)

References 77 publications

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“…And OPN-KO mice formed a few crystals less than WT mice after 3 days in renal cortex-medulla junction. OPN is reportedly related to human kidney stones [37,38]. Evan et al reported [39] that OPN is one of the crystal-associated urine proteins involved in the formation of the organic layers of human kidney plaque particles.…”

Section: Discussionmentioning

confidence: 99%

Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice

et al. 2011

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Osteopontin (OPN) is an important matrix protein of renal calcium stone. However, the function of OPN in the early phase of renal crystal formation is not well defined. In this study, we examined OPN expression in the early phase of renal crystal formation with ultra-microstructural observations and immuno-TEM (transmission electron microscopy) in control and OPN knock-out (OPN-KO) mice. Glyoxylate (100 mg/kg) was intra-abdominally administered to male wild-type mice (C57BL/6, 8 weeks of age) and OPN-KO mice (C57BL/6, 8 weeks of age). Kidney was collected before and 6, 12, and 24 h after administration. We examined the relation between renal crystal formation and microstructural OPN location using TEM and immunohistochemical staining of OPN as well as western blotting and quantitative RT-PCR for OPN. OPN protein expression gradually increased in the renal cortex-medulla junction after glyoxylate administration, and OPN mRNA was increased until 12 h, but decreased at 24 h. In ultra-microstructural observation, OPN began to appear on the luminal side of renal distal tubular cells at 6 h and was gradually detected in the tubular lumen at 12 h. OPN was present in the crystal nuclei and collapsed mitochondria in the tubular lumen. In the OPN-KO mice, collapsed mitochondria were present, but no crystal nuclei formation were detected at 24 h. Based on the results this study proposed that the appearance of organelles, such as mitochondria and microvilli, in the tubular lumen after cell injury may be the starting point of crystal nucleus formation due to the aggregation ability of OPN.

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Section: Discussionmentioning

confidence: 99%

Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice

et al. 2011

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“…Osteopontin is a cytokine made by T cells and macrophages that is also involved in calcification. 24,25 This may be a link between inflammation and calcification. From our review of the literature, the aforementioned findings are novel.…”

Section: Discussionmentioning

confidence: 99%

Glutaraldehyde-Fixed Bioprosthetic Heart Valve Conduits Calcify and Fail From Xenograft Rejection

et al. 2006

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Background— Glutaraldehyde fixation (G-F) decreases but likely does not eliminate the antigenicity of bioprosthetic heart valves. Rejection (with secondary dystrophic calcification) may be why G-F xenograft valves fail, especially in young patients, who are more immunocompetent than the elderly. Therefore, we sought to determine whether rejection of G-F xenograft occurs and to correlate this with graft calcification. Methods and Results— Ascending aortas/valves (from rats [syngeneic] or guinea pigs [xenogeneic]) were transplanted (fresh or after 48 hour of G-F) into the infrarenal aortas of young rat recipients for 20 days. A xenogeneic group was also treated with steroids until graft harvest. The valves and media/adventitia were scored blindly for inflammation (0 to 4). Percent graft infiltration by T cells/macrophages was determined (immunohistochemistry), and rat IgG ELISAs were performed. There was >3 times more valve inflammation, >10 times more valve T-cell/macrophage infiltrate, and >3 times antibody rise in the G-F xenogeneic groups compared with the fresh syngeneic or the G-F syngeneic groups ( P <0.05). There was >2 times more adventitial inflammation and T-cell/macrophage infiltrate in the xenogeneic groups ( P <0.05). Steroid treatment decreased inflammation and antibody rise in the xenogeneic groups ( P <0.05). Correlation analysis revealed media/adventitia inflammation ( P =0.02) and percent macrophage ( P =0.01) infiltration to be predictors of calcification. Conclusions— G-F xenografts have cellular/humoral rejection and calcify secondarily.

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“…They concluded that these proteins promote the formation of calcium oxalate stone. However, a study from stone former urine by Kleinman et al (28) found that osteopontin has endogenous defense against crystal formation. Osteopontin acts in vivo primarily to inhibit the retention of crystal rather than to retard crystal nucleation, growth, or aggregation from a preliminary data of Kleinman et al (28).…”

Section: Discussionmentioning

confidence: 99%

“…However, a study from stone former urine by Kleinman et al (28) found that osteopontin has endogenous defense against crystal formation. Osteopontin acts in vivo primarily to inhibit the retention of crystal rather than to retard crystal nucleation, growth, or aggregation from a preliminary data of Kleinman et al (28). Osteopontin found in stone maybe cause by its adsorption on crystal surface to prevent further crystal adhesion thereby as an inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Mass spectroscopic characteristics of low molecular weight proteins extracted from calcium oxalate stones: preliminary study

Chen

Lai

Tsai

et al. 2008

Clinical Laboratory Analysis

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It is believed that boundary compositions of matrix proteins might play a role in stone formation; however, few proteomic studies concerning matrix proteins in urinary stones have been conducted. In this study, we extracted low molecular weight proteins from calcium oxalate stones and measured their characteristic patterns by mass spectroscopy. A total of 10 stones were surgically removed from patients with urolithiasis. Proteins were extracted from the stones and identified by one‐dimensional electrophoresis (sodium dodecyl sulfate buffer [SDS]–polyacrylamide gel electrophoresis [SDS‐PAGE]). After in‐gel digest, samples were analyzed by the surface‐enhanced laser desorption ionization‐time of flight (SELDI‐TOF) technique. The peptide sequences were analyzed from the data of mass spectroscopy. Proteins were identified from Database Search (SwissProt Protein Database; Swiss Institute of Bioinformatics; http://www.expasy.org/sprot) on a MASCOT server (Matrix Science Ltd.; http://www.matrixscience.com). A total of three bands of proteins (27, 18, and 14 kDa) were identified from SDS‐PAGE in each stone sample. A database search (SwissProt) on a MASCOT server revealed that the most frequently seen proteins from band 1 (27 kDa) were leukocyte elastase precursor, cathepsin G precursor, azurocidin precursor, and myeloblastin precursor (EC 3.4.21.76) (leukocyte proteinase 3); band 2 (18 kDa) comprised calgranulin B, eosinophil cationic protein precursor, and lysozyme C precursor; band 3 (14 kDa) showed neutrophil defensin 3 precursor, calgranulin A, calgranulin C, and histone H4. The modifications and deamidations found from the mass pattern of these proteins may provide information for the study of matrix proteins. Various lower molecular weight proteins can be extracted from calcium oxalate stones. The characteristic patterns and their functions of those proteins should be further tested to investigate their roles in stone formation. J. Clin. Lab. Anal. 22:77–85, 2008. © 2008 Wiley‐Liss, Inc.

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Osteopontin and Calcium Stone Formation

Cited by 69 publications

References 77 publications

Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice

Role of osteopontin in early phase of renal crystal formation: immunohistochemical and microstructural comparisons with osteopontin knock-out mice

Glutaraldehyde-Fixed Bioprosthetic Heart Valve Conduits Calcify and Fail From Xenograft Rejection

Mass spectroscopic characteristics of low molecular weight proteins extracted from calcium oxalate stones: preliminary study

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