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Saeed R Khan - One of the best experts on this subject based on the ideXlab platform.
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Pathogenesis of Calcium Oxalate urinary stone disease: species comparison of humans, dogs, and cats
Urolithiasis, 2017Co-Authors: Allison L. O’kell, David C. Grant, Saeed R KhanAbstract:Idiopathic Calcium Oxalate nephrolithiasis is a highly recurrent disease that is increasing in prevalence. Decades of research have not identified effective methods to consistently prevent the formation of nephroliths or induce medical dissolution. Idiopathic Calcium Oxalate nephroliths form in association with renal papillary subepithelial Calcium phosphate deposits called Randall’s plaques (RPs). Rodent models are commonly used to experimentally induce Calcium Oxalate crystal and stone formation, but a rodent model that conclusively forms RPs has not been identified. Both dogs and cats form Calcium Oxalate uroliths that can be recurrent, but the etiopathologic mechanisms of stone formation, especially renal pathologic findings, are a relatively unexploited area of study. A large animal model that shares a similar environment to humans, along with a shorter lifespan and thus shorter time to recurrence, might provide an excellent means to study preventative and therapeutic measures, along with enhancing the concepts of the one health initiative. This review article summarizes and compares important known features of idiopathic Calcium Oxalate stone disease in humans, dogs, and cats, and emphasizes important knowledge gaps and areas for future study in the quest to discover a naturally occurring animal model of idiopathic Calcium Oxalate stone disease.
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Calcium Oxalate stone fragment and crystal phagocytosis by human macrophages
The Journal of Urology, 2016Co-Authors: Sergei Kusmartsev, Paul R Dominguezgutierrez, Benjamin K Canales, Vincent G Bird, Johannes Vieweg, Saeed R KhanAbstract:Purpose: In murine and human hyperoxaluric conditions macrophages can be seen surrounding renal Calcium Oxalate crystal deposits. We hypothesized that macrophages have a role in degrading and destroying these deposits. We investigated the inflammatory response and phagocytic mechanisms when macrophages were exposed to human kidney stones and inorganic crystals.Materials and Methods: Human monocytes were differentiated into resting, fully differentiated macrophages by treatment with recombinant human macrophage colony-stimulating factor (M-CSF) or GM-CSF (granulocyte M-CSF) for 6 days. After confirming phenotype by flow cytometry the macrophages were exposed for 20 hours to fragments of sterile human Calcium Oxalate stones or Calcium Oxalate crystals. Crystal uptake was determined, and supernatant cytokine and chemokine profiles were analyzed using antibody arrays. Quantitative reverse transcriptase-polymerase chain reaction was done to validate mRNA profile expression.Results: Under direct vision fluoresc...
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experimental induction of Calcium Oxalate nephrolithiasis in mice
The Journal of Urology, 2010Co-Authors: Saeed R Khan, Patricia A GlentonAbstract:Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of Calcium Oxalate stone disease. However, attempts to produce Calcium Oxalate nephrolithiasis in mice have not been successful. We hypothesized that Calcium Oxalate nephrolithiasis in mice requires increasing urine Calcium and Oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis.Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a −/− mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase Calcium and Oxalate. Kidney...
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expression of osteopontin in rat kidneys induction during ethylene glycol induced Calcium Oxalate nephrolithiasis
The Journal of Urology, 2002Co-Authors: Saeed R Khan, Joanne M Johnson, Ammon B Peck, Janet G Cornelius, Patricia A GlentonAbstract:ABSTRACTPurpose: Osteopontin is a well-known component of stone matrix and a strong inhibitor of the nucleation, growth and aggregation of Calcium Oxalate crystals in vitro. To understand its involvement in vivo in Calcium Oxalate nephrolithiasis we investigated the renal expression and urinary excretion of osteopontin in normal rats, and rats with hyperoxaluria and Calcium Oxalate crystal deposits in the kidneys.Materials and Methods: Calcium Oxalate nephrolithiasis was induced by administering ethylene glycol. Immunohistochemistry and in situ hybridization were done to localize osteopontin and osteopontin messenger RNA in the kidneys, while sensitive reverse transcriptase quantitative competitive template polymerase chain reaction was performed to detect and quantify osteopontin messenger RNA expression. Urinary excretion was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis, and then quantified by densitometry of the Western blots.Results: Osteopontin exp...
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effects of an extract from herniaria hirsuta on Calcium Oxalate crystallization in vitro
BJUI, 2001Co-Authors: Fouad Atmani, Saeed R KhanAbstract:Objective To evaluate the effectiveness of an extract obtained from Herniaria hirsuta on Calcium Oxalate crystallization in vitro. Materials and methods An extract was prepared from H. hirsuta at different concentrations (0.0625–1 mg/mL). Crystallization was induced in whole normal human urine samples in the absence or presence of the extract. Crystals generated in the urine were harvested and analysed by scanning electron microscopy. The nucleation and aggregation of Calcium Oxalate crystals were measured separately using spectrophotometric methods. The nucleation rate was followed at 620 nm after mixing Calcium chloride and sodium Oxalate solution at 37 °C, with stirring. The induction time in the presence of herb extract was compared with that of the control. The aggregation rate was also followed at 620 nm in a buffered solution containing Calcium Oxalate monohydrate crystals after stopping the stirring. The rate was evaluated by comparing the slope of turbidity in the presence of the extract with that of the control. Results The herb extract promoted the precipitation of Calcium Oxalate particles in whole urine. sem showed that there were more crystals with increasing concentration of extract but that they were proportionally smaller. Moreover, the presence of herb extract favoured the formation of Calcium Oxalate dihydrate rather than monohydrate crystals. The extract inhibited Calcium Oxalate crystal aggregation. In an independent experiment, the herb extract was dialysed and filtered before inducing crystallization, to eliminate any fibrous particles and Oxalate. The treated herb extract promoted more crystallization, especially at high concentrations. Conclusion An extract of H. hirsuta promoted the nucleation of Calcium Oxalate crystals, increasing their number but decreasing their size. It also promoted the formation of Calcium Oxalate dihydrate crystals, despite the presence of Calcium Oxalate monohydrate particles. The extract may contain substances that inhibit Calcium Oxalate crystal aggregation. These properties of H. hirsuta might be beneficial in preventing kidney stone formation.
Roswitha Siener - One of the best experts on this subject based on the ideXlab platform.
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The role of Oxalobacter formigenes in Calcium Oxalate stone disease
2017Co-Authors: Roswitha SienerAbstract:Calcium Oxalate is the major component of about 75% of all urinary stones. Hyperoxaluria is a primary risk factor for Calcium Oxalate stone formation. The bioavailability of ingested Oxalate and the extent of intestinal absorption of dietary Oxalate are considered to be important factors in hyperoxaluria. Oxalobacter formigenes is a Gram-negative anaerobic bacterium that colonizes the intestinal tract. It is unique in that it requires Oxalate both as an energy and carbon source. The only known factor which reduces colonization with O. formigenes is the treatment with antibiotics to which the bacterium has been reported to be sensitive. A deficiency of Oxalate degradation by O. formigenes may increase urinary Oxalate excretion, attributed to decreased intestinal Oxalate degradation, leaving more Oxalate available for absorption at a constant intestinal absorption rate. A lack of colonization with O. formigenes increases the risk of recurrent Calcium Oxalate stone formation. While evidence is emerging that orally administered O. formigenes can reduce urinary and plasma Oxalate, the possible treatment with a probiotic still remains a challenge.
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the efficacy of dietary intervention on urinary risk factors for stone formation in recurrent Calcium Oxalate stone patients
The Journal of Urology, 2005Co-Authors: Roswitha Siener, Claudia Nicolay, Natalie Schade, Gerd E Von Unruh, A HesseAbstract:ABSTRACT Purpose: Nutrition is suggested to be the major environmental risk factor in idiopathic Calcium Oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in Calcium Oxalate stone formers. Materials and Methods: A total of 76 men and 31 women with idiopathic Calcium Oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for Calcium Oxalate stone formers. Results: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of Calcium Oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary Calcium and uric acid excretion. No change occurred in urinary Oxalate and magnesium excretion. Conclusions: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for Calcium Oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for Calcium Oxalate stone formers significantly reduced the stone forming potential.
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The role of overweight and obesity in Calcium Oxalate stone formation.
Obesity Research, 2004Co-Authors: Roswitha Siener, Sara Glatz, Claudia Nicolay, A HesseAbstract:Objective: The aim of the study was to assess the influence of overweight and obesity on the risk of Calcium Oxalate stone formation. Research Methods and Procedures: BMI, 24-hour urine, and serum parameters were evaluated in idiopathic Calcium Oxalate stone formers (363 men and 164 women) without medical or dietetic pretreatment. Results: Overweight and obesity were present in 59.2% of the men and in 43.9% of the women in the study population. Multiple linear regression analysis revealed a significant positive relationship between BMI and urinary uric acid, sodium, ammonium, and phosphate excretion and an inverse correlation between BMI and urinary pH in both men and women, whereas BMI was associated with urinary Oxalate excretion only among women and with urinary Calcium excretion only among men. Serum uric acid and creatinine concentrations were correlated with BMI in both genders. Because no association was established between BMI and urinary volume, magnesium, and citrate excretion, inhibitors of Calcium Oxalate stone formation, the risk of stone formation increased significantly with increasing BMI among both men and women with urolithiasis (p = 0.015). The risk of Calcium Oxalate stone formation, median number of stone episodes, and frequency of diet-related diseases were highest in overweight and obese men. Discussion: Overweight and obesity are strongly associated with an elevated risk of stone formation in both genders due to an increased urinary excretion of promoters but not inhibitors of Calcium Oxalate stone formation. Overweight and obese men are more prone to stone formation than overweight women.
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Dietary risk factors for hyperoxaluria in Calcium Oxalate stone formers
Kidney international, 2003Co-Authors: Roswitha Siener, Claudia Nicolay, Dagmar Ebert, A HesseAbstract:Dietary risk factors for hyperoxaluria in Calcium Oxalate stone formers. Background Hyperoxaluria is a major predisposing factor in Calcium Oxalate urolithiasis. The aim of the present study was to clarify the role of dietary Oxalate in urinary Oxalate excretion and to assess dietary risk factors for hyperoxaluria in Calcium Oxalate stone patients. Methods Dietary intakes of 186 Calcium Oxalate stone formers, 93 with hyperoxaluria (≥0.5 mmol/day) and 93 with normal Oxalate excretion ( Results The mean daily intakes of energy, total protein, fat and carbohydrates were similar in both groups. The diets of the patients with hyperoxaluria were estimated to contain 130 mg/day Oxalate and 812 mg/day Calcium as compared to 101 mg/day Oxalate and 845 mg/day Calcium among patients without hyperoxaluria. These differences were not significant. The mean daily intakes of water (in food and beverages), magnesium, potassium, dietary fiber and ascorbic acid were greater in patients with hyperoxaluria than in stone formers with normal Oxalate excretion. Multiple logistic regression analysis revealed that urinary Oxalate excretion was significantly associated with dietary ascorbate and fluid intake, and inversely related to Calcium intake. Differences of estimated diet composition of both groups corresponded to differences in urinary parameters. Conclusions These findings suggest that hyperoxaluria predominantly results from increased endogenous production and from intestinal hyperabsorption of Oxalate, partly caused by an insufficient supply or low availability of Calcium for complexation with Oxalate in the intestinal lumen.
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the effect of different diets on urine composition and the risk of Calcium Oxalate crystallisation in healthy subjects
European Urology, 2002Co-Authors: Roswitha Siener, A HesseAbstract:Abstract Objective: The aim of the study was to determine the impact of defined diet modifications on urine composition and the risk of Calcium Oxalate crystallisation. Methods: Ten healthy male volunteers consumed a self-selected diet (SD) for 14 days, and three different standard diets for a period of 5 days each. Whereas the western-type diet (WD) is representative of the usual dietary habits, the normal mixed diet (ND) and the ovo-lacto-vegetarian diet (VD) were calculated according to the requirements. Results: The risk of Calcium Oxalate crystallisation, calculated as relative supersaturation (EQUIL2) from urine composition, was highest during ingestion of diets SD and WD. The intake of diet ND resulted in a significant decrease in relative supersaturation with Calcium Oxalate by 58% ( p p Conclusions: The change of usual dietary habits for a normal mixed diet significantly reduces the risk of Calcium Oxalate crystallisation. With a vegetarian diet a similar decline in urinary supersaturation with Calcium Oxalate can be achieved compared to a normal mixed diet. Since urinary Oxalate excretion increased significantly, a vegetarian diet without adequate intake of Calcium may not be recommended to patients with mild hyperoxaluria.
A Hesse - One of the best experts on this subject based on the ideXlab platform.
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the efficacy of dietary intervention on urinary risk factors for stone formation in recurrent Calcium Oxalate stone patients
The Journal of Urology, 2005Co-Authors: Roswitha Siener, Claudia Nicolay, Natalie Schade, Gerd E Von Unruh, A HesseAbstract:ABSTRACT Purpose: Nutrition is suggested to be the major environmental risk factor in idiopathic Calcium Oxalate stone disease. The study was designed to evaluate the effect of dietary intervention on urinary risk factors for recurrence in Calcium Oxalate stone formers. Materials and Methods: A total of 76 men and 31 women with idiopathic Calcium Oxalate stone disease collected 24-hour urine on their habitual, self-selected diets and after 7 days on a balanced standardized diet according to the recommendations for Calcium Oxalate stone formers. Results: On the usual diet, a urine volume of less than 2.0 l per 24 hours was present in 57.9%, hypercalciuria in 25.2%, hypomagnesuria in 18.7%, hyperoxaluria in 14.0%, hyperuricosuria in 41.3% and hypocitraturia in 57.0% of patients. The frequency of metabolic abnormalities and the risk of Calcium Oxalate stone formation decreased significantly on the ingestion of the balanced diet, due to the significant increase in urinary volume, pH and citrate excretion and the significant decrease in urinary Calcium and uric acid excretion. No change occurred in urinary Oxalate and magnesium excretion. Conclusions: The evaluation of urinary risk profiles of the patients on their usual dietary habits revealed a high risk for Calcium Oxalate stone formation. A low fluid intake and an increased intake of protein and alcohol were identified as the most important dietary risk factors. The shift to a nutritionally balanced diet according to the recommendations for Calcium Oxalate stone formers significantly reduced the stone forming potential.
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the effect of different diets on urine composition and the risk of Calcium Oxalate crystallisation in healthy subjects
European Urology, 2002Co-Authors: Roswitha Siener, A HesseAbstract:Abstract Objective: The aim of the study was to determine the impact of defined diet modifications on urine composition and the risk of Calcium Oxalate crystallisation. Methods: Ten healthy male volunteers consumed a self-selected diet (SD) for 14 days, and three different standard diets for a period of 5 days each. Whereas the western-type diet (WD) is representative of the usual dietary habits, the normal mixed diet (ND) and the ovo-lacto-vegetarian diet (VD) were calculated according to the requirements. Results: The risk of Calcium Oxalate crystallisation, calculated as relative supersaturation (EQUIL2) from urine composition, was highest during ingestion of diets SD and WD. The intake of diet ND resulted in a significant decrease in relative supersaturation with Calcium Oxalate by 58% ( p p Conclusions: The change of usual dietary habits for a normal mixed diet significantly reduces the risk of Calcium Oxalate crystallisation. With a vegetarian diet a similar decline in urinary supersaturation with Calcium Oxalate can be achieved compared to a normal mixed diet. Since urinary Oxalate excretion increased significantly, a vegetarian diet without adequate intake of Calcium may not be recommended to patients with mild hyperoxaluria.
Paul A Nakata - One of the best experts on this subject based on the ideXlab platform.
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Plant Calcium Oxalate crystal formation, function, and its impact on human health
Frontiers in Biology, 2012Co-Authors: Paul A NakataAbstract:Crystals of Calcium Oxalate have been observed among members from most taxonomic groups of photosynthetic organisms ranging from the smallest algae to the largest trees. The biological roles for Calcium Oxalate crystal formation in plant growth and development include high-capacity Calcium regulation, protection against herbivory, and tolerance to heavy metals. Using a variety of experimental approaches researchers have begun to unravel the complex mechanisms controlling formation of this biomineral. Given the important roles for Calcium Oxalate formation in plant survival and the antinutrient and pathological impact on human health through its presence in plant foods, researchers are avidly seeking a more comprehensive understanding of how these crystals form. Such an understanding will be useful in efforts to design strategies aimed at improving the nutritional quality and production of plant foods.
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medicago truncatula mutants demonstrate the role of plant Calcium Oxalate crystals as an effective defense against chewing insects
Plant Physiology, 2006Co-Authors: Kenneth L Korth, Sarah J Doege, Sanghyuck Park, Fiona L Goggin, Qin Wang, Karen S Gomez, Guangjie Liu, Lingling Jia, Paul A NakataAbstract:Calcium Oxalate is the most abundant insoluble mineral found in plants and its crystals have been reported in more than 200 plant families. In the barrel medic Medicago truncatula Gaertn., these crystals accumulate predominantly in a sheath surrounding secondary veins of leaves. Mutants of M. truncatula with decreased levels of Calcium Oxalate crystals were used to assess the defensive role of this mineral against insects. Caterpillar larvae of the beet armyworm Spodoptera exigua Hubner show a clear feeding preference for tissue from Calcium Oxalate-defective (cod) mutant lines cod5 and cod6 in choice test comparisons with wild-type M. truncatula. Compared to their performance on mutant lines, larvae feeding on wild-type plants with abundant Calcium Oxalate crystals suffer significantly reduced growth and increased mortality. Induction of wound-responsive genes appears to be normal in cod5 and cod6, indicating that these lines are not deficient in induced insect defenses. Electron micrographs of insect mouthparts indicate that the prismatic crystals in M. truncatula leaves act as physical abrasives during feeding. Food utilization measurements show that, after consumption, Calcium Oxalate also interferes with the conversion of plant material into insect biomass during digestion. In contrast to their detrimental effects on a chewing insect, Calcium Oxalate crystals do not negatively affect the performance of the pea aphid Acyrthosiphon pisum Harris, a sap-feeding insect with piercing-sucking mouthparts. The results confirm a long-held hypothesis for the defensive function of these crystals and point to the potential value of genes controlling crystal formation and localization in crop plants.
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advances in our understanding of Calcium Oxalate crystal formation and function in plants
Plant Science, 2003Co-Authors: Paul A NakataAbstract:Abstract Calcium Oxalate crystal formation in plants appears to play a central role in a variety of important functions, including tissue Calcium regulation, protection from herbivory, and metal detoxification. Evidence is mounting to support ascorbic acid as the primary precursor to Oxalate biosynthesis. The ascorbic acid utilized in Oxalate biosynthesis is synthesized directly within the Calcium Oxalate crystal-accumulating cell, called the crystal idioblast. Several unique features of the crystal idioblast have been proposed as factors that influence Calcium Oxalate formation. These features include an abundance of endoplasmic reticulum (ER), acidic proteins, cytoskeletal components, and the intravacuolar matrix. A number of mutants defective in different aspects of Calcium Oxalate crystal formation have been isolated. Cellular and biochemical characterizations of the various mutants have revealed mutations affecting crystal nucleation, morphology, distribution, and/or amount. Such mutants will be useful tools in continued efforts to decipher the pathways of crystal formation and function in plants.
Patricia A Glenton - One of the best experts on this subject based on the ideXlab platform.
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experimental induction of Calcium Oxalate nephrolithiasis in mice
The Journal of Urology, 2010Co-Authors: Saeed R Khan, Patricia A GlentonAbstract:Purpose: The availability of various transgenic and knockout mice provides an excellent opportunity to better understand the pathophysiology of Calcium Oxalate stone disease. However, attempts to produce Calcium Oxalate nephrolithiasis in mice have not been successful. We hypothesized that Calcium Oxalate nephrolithiasis in mice requires increasing urine Calcium and Oxalate excretion, and experimentally induced hyperoxaluria alone is not sufficient. To provide evidence we induced hyperoxaluria by administering hyperoxaluria inducing agents in normocalciuric and hypercalciuric mice, and investigating various aspects of nephrolithiasis.Materials and Methods: We administered ethylene glycol, glyoxylate or hydroxyl proline via diet in male and female normocalciuric B6 mice, and in hypercalciuric sodium phosphate co-transporter type 2 a −/− mice for 4 weeks. We collected 24-hour urine samples on days 0, 3, 7, 14, 21 and 28, and analyzed them for pH, creatinine, lactate dehydrogenase Calcium and Oxalate. Kidney...
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expression of osteopontin in rat kidneys induction during ethylene glycol induced Calcium Oxalate nephrolithiasis
The Journal of Urology, 2002Co-Authors: Saeed R Khan, Joanne M Johnson, Ammon B Peck, Janet G Cornelius, Patricia A GlentonAbstract:ABSTRACTPurpose: Osteopontin is a well-known component of stone matrix and a strong inhibitor of the nucleation, growth and aggregation of Calcium Oxalate crystals in vitro. To understand its involvement in vivo in Calcium Oxalate nephrolithiasis we investigated the renal expression and urinary excretion of osteopontin in normal rats, and rats with hyperoxaluria and Calcium Oxalate crystal deposits in the kidneys.Materials and Methods: Calcium Oxalate nephrolithiasis was induced by administering ethylene glycol. Immunohistochemistry and in situ hybridization were done to localize osteopontin and osteopontin messenger RNA in the kidneys, while sensitive reverse transcriptase quantitative competitive template polymerase chain reaction was performed to detect and quantify osteopontin messenger RNA expression. Urinary excretion was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis, and then quantified by densitometry of the Western blots.Results: Osteopontin exp...
