Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bone contains a small protein, osteocalcin, rich in the amino acid gamma-carboxyglutamate (gammaCGlu), which is dependent on vitamin K for its synthesis. The vitamin K dependence of osteocalcin biosynthesis has been studied both in the developing chicken embryo and in the skeletons of young chicks. Osteocalcin formation, assessed by quantitation of gammaCGlu in whole bone, begins in the 8-day embryonic skeleton and increases dramatically until hatching. Biosynthesis of gammaCGlu is warfarinsensitive; time- and dose-related inhibition of up to 75% is observed. Vitamin K deficiency reduces bone gammaCGlu concentrations by 50% in 3-week-old chicks, and this is totally corrected by including vitamin K1 in the diet. Feeding the vitamin K antagonist dicumarol decreases the bone gammaCGlu level 80% after 6 weeks, but no corresponding alterations are observed in the calcium and phosphorous content of the bone ash. Osteocalcin purified from bones of dicumoral-fed chicks exhibits several electrophoretically variant undercarboxylated protein species containing 2 and 3 gammaCGlu/57 amino acid residues rather than the normal complement of 4 gammaCGlu/57 residues.
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PMID:Vitamin K dependence of a calcium-binding protein containing gamma-carboxyglutamic acid in chicken bone. 72 29

In antrectomized (B-I) and control rats, bone mineralization, the fractional intestinal absorption of calcium, magnesium and phosphorus, the balances of these minerals, their serum concentration and renal excretion, together with serum gastrin, calciotropic hormones (parathyroid hormone, calcitonin, 1,25-dihydroxyvitamin D), and osteocalcin were assessed four months after surgery. B-I evoked hypogastrinemia, but no changes in the serum concentrations of minerals and calciotropic hormones, or urinary cyclic AMP. The major significant changes brought about by B-I were: (1) a decrease in bone dry weight, specific density, bone ash calcium and magnesium content; (2) a decrease in the fractional absorption and urinary excretion of calcium and magnesium; (3) an increase in urinary hydroxyproline and serum osteocalcin in the presence of normal serum bone isoenzyme of alkaline phosphatase. It is concluded that in the rat (1) B-I over the long term decreases both bone mineral content and calcium and magnesium absorption, in the absence of any counterregulation; (2) B-I rats may have attained a new equilibrium which is characterized by decreased absorption and urinary excretion of calcium and magnesium, but maintenance of normocalcemia at the expense of bone; (3) the concomitant changes of serum bone markers are contradictory, which makes their interpretation and use in the present context difficult.
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PMID:Disturbances of mineral and bone metabolism following gastric antrectomy in the rat. 133 20

The relation between bone mineralization and osteocalcin content was investigated in iliac crest cortical bone obtained at necropsy in young females and in two groups of elderly women with and without osteoarthritis of the hands evaluated by X-ray. Using density fractionation technique, the bone was separated into fractions of increasing density from 1.72 to 2.30 g/ml. The mineralization profile revealed a significant shift to higher densities in the osteoarthritis cases compared with young adults (P less than 0.005) and age-sex-matched controls (P less than 0.001). The ash, calcium, and phosphorus content of the bone increased with increasing density of the fractions whereas collagen content, measured as hydroxyproline, decreased. The osteocalcin concentration of each fraction was determined in the supernatants obtained after EDTA-extraction in the presence of protease inhibitors. In the young control and osteoarthritis group, the osteocalcin content in the lowest density fractions was higher compared with the older non-osteoarthritic group. Osteocalcin content of the high density fractions, representing highly mineralized osteons, was the same in the three groups studied. These findings support the hypothesis that quality differences in bone may explain the inverse relationship between osteoarthritis and osteoporosis.
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PMID:Alterations of the mineralization profile and osteocalcin concentrations in osteoarthritic cortical iliac crest bone. 142 71

Serum osteocalcin was remarkably and significantly (-34 and -41% in two separate experiments; p less than 0.001) lower in rats fed an 8% (w/v) ethanol liquid diet (ELD) for 1 week than in rats fed an isocaloric control liquid diet (CLD). In a longer experiment that spanned 4 weeks, the ELD rats were given 6% ethanol on day 4, increased stepwise to 8% by day 9, and then maintained at 8% until day 28, when the experiment was terminated. Again, serum osteocalcin was much lower (-32%, p less than 0.001) in the ELD-fed rats than in CLD-fed rats. Even in rats fed only a 6% ELD for 12 days, serum osteocalcin was lower (-33%, p less than 0.001) than in controls. Also, the femora were weaker, more compliant, and more ductile in ELD-than in CLD-fed rats, findings that confirmed our earlier, related work. The fall in serum osteocalcin in ELD-fed rats is associated with a fall in femur ash weight and bone strength. There were significant correlations between serum osteocalcin and bone strength (r = 0.80; p less than 0.001) and between serum osteocalcin and bone stiffness (r = 0.83; p less than 0.001). Serum ionized calcium, like osteocalcin, was consistently lower in rats given ethanol for 1 or 4 weeks than in controls. From these experiments we conclude that excessive ethanol consumption inhibits osteoblastic activity as indicated by the reduced serum osteocalcin. The inhibition is also associated with other deleterious effects of ethanol on bone, including ash weight, bone strength, and bone stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lower serum osteocalcin in ethanol-fed rats. 202 32

The long-term effects of experimentally induced diabetes on bone were studied in eight male Lewis rats, intravenously (i.v.) injected with 65 mg/kg of streptozocin (STZ) and maintained for 12 months. Eight untreated age-matched rats served as controls. In the STZ-treated rats, experimentally induced diabetes was documented by the presence of hyperglycemia at 24 h and at 3 and 12 months. Significantly less weight was gained and less growth occurred in the STZ-treated rats despite careful attention to feeding and hydration. Mineral alterations were detected in the bones of the animals with experimental diabetes. Decreased hydroxyapatite crystal perfection, decreased Ca/P of the ash, and decreased ash content in the tibial metaphyses with increased ash content in the tibial diaphyses, was noted relative to controls. Bone osteocalcin content was increased in the metaphyses of the STZ-treated rats. While absolute measures of stiffness, torsional strength and energy absorption were decreased in the bones of the STZ-treated animals, when torsional strength and stiffness were normalized for differences in both growth and geometry, the normalized stiffness values for the diabetic bones were increased. The results suggest that in experimental diabetes certain aspects of bone mineralization are adversely affected and lead to reduced strength-related properties. However, a compensatory increase in stiffness occurs. The reason for this increase, although not known, may be related to changes in bone crystal structure.
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PMID:The mineral and mechanical properties of bone in chronic experimental diabetes. 276 Jul 51

The present paper intends to check the possibility of improving convenience of the osteoporosis model from ovariectomy in the rat by anticipating the operation to the 40th week rather than the 52nd week of age, thought by some authors to be the optimum model. To this end two parameters have been examined: 1. the bone mass variation determined with the vertebral photon densitometer and weighing of the femur ashes; 2. the chemico-crystallographic characteristics of the bone determined through chemical analysis and X-ray diffractometry. The results obtained induce us to believe that ovariectomy carried out on rats of 40 or 52 weeks of age determine bone mass losses that are statistically comparable. The variations in the dry bone weight/ash bone weight ratio are superposable and the structural chemical characteristics, due to the increase in bone turnover are testified by the increase in osteocalcin. Moreover, it was observed that the most reliable evaluation of bone mass loss can be obtained with the vertebral photon densitometry. Thus, it is thought that the model which foresees ovariectomy of rats 40 weeks after birth compared with those operated 52 weeks after birth, represents a good model of osteoporosis from estrogen deficiency which, due to the evident practical advantages deriving from the use of younger animals it associates a decrease in the use of laboratory animals with statistically reliable results.
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PMID:Evaluation of an experimental model of osteoporosis induced in the female rat through ovariectomy. 815 3

Androgens have important effects on bone in vivo, possibly by direct activation of the androgen receptors in osteoblasts. To test this hypothesis, calcium homeostasis, bone mass, and bone turnover were evaluated in mature (4-month-old) androgen-resistant (testicular feminized, TFM) male rats. Data were compared with data from both female and male littermates of the same age and strain. Compared to normal males, TFM had similar serum testosterone, twofold higher estradiol and estrone, and sixfold higher androstenedione concentrations. Compared to normal females, TFM rats showed lower estradiol but also elevated concentrations of androstenedione and estrone. Despite similar free 1,25-(OH)2D3 concentrations, both TFM and male rats maintained higher serum calcium and phosphate concentrations than their female littermates. Serum IGF-I concentrations in TFM rats were decreased compared to male rats (-12%) or female rats (-27%). Serum osteocalcin concentrations, however, were twofold higher in TFM rats than in females but not significantly different from males. Femoral length, diameter, and cortical thickness were intermediate between those of males and females. The cancellous bone density of the femur and cancellous bone volume of the proximal metaphysis of the tibia, however, were not significantly different between groups. The ash weight of the tibia was also not significantly different, and the ash weight of the four distal lumbar vertebrae ranged between male and female values. Bone mechanical properties as measured by torsional strength and energy absorption of the femur were lower in TFM than in females but not different from males.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bone and mineral metabolism in the androgen-resistant (testicular feminized) male rat. 835 63

The effects of dietary calcium intake on vertebral bone mass, composition, and turnover (calcium deposition and resorption) were determined in 10- and 14-week-old C57BL/6 (small) and SENCAR (large) mice. Total vertebral mass, percent ash, calcium, magnesium, and phosphorus were higher in SENCAR mice than in C57BL/6 mice at 10 weeks of age and after being fed 0.02% or 0.6% dietary calcium for 4 additional weeks. Relative calcium deposition was higher in C57BL/6 than in SENCAR mice, while relative calcium resorption was similar in both strains. The rate of resorption was higher in mice fed 0.02% dietary calcium than in those fed 0.6% dietary calcium. Thus, C57BL/6 mice gained vertebral calcium, while it remained unchanged or declined in SENCAR mice under conditions of both calcium depletion and calcium repletion. Serum osteocalcin (an index of bone formation) was higher in C57BL/6 mice than in SENCAR mice. Mathematically significant correlations between osteocalcin levels and vertebral calcium resorption and the net vertebral calcium loss were observed only in SENCAR mice. The serum calcitonin concentration was correlated with the amount of vertebral calcium resorbed in SENCAR mice, but not in C57BL/6 mice. Thus, vertebral resorption and formation are more tightly coupled in 10- to 14-week-old SENCAR mice than in C57BL/6 mice. In addition, remodeling appears to dominate vertebral calcium dynamics in SENCAR mice, while growth dominates in C57BL/6 mice during this period. Rodents have frequently been dismissed as potential models of bone aging based on the expectation that continued growth, rather than remodeling, dominates skeletal dynamics. These data clearly demonstrate that increases in body mass ("growth") are not invariably associated with continued vertebral growth. In this murine model, both heredity and dietary calcium intake modulate vertebral bone mass, turnover dynamics, and composition at sexual maturity. These differences in the development and regulation of vertebral bone mass in small C57BL/6 and large SENCAR mice suggest that animal, as well as clinical, models provide useful insights into the cellular and hormonal mechanisms of somatotype-dependent vertebral growth.
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PMID:Strain-dependent differences in vertebral bone mass, serum osteocalcin, and calcitonin in calcium-replete and -deficient mice. 847 40

We have further investigated the "meal effect" on mineral bioavailability in pigs by mineral balance studies and measurements of bone ash contents and bending moment. A group of seven pigs (CAA) was given all its dietary Ca as CaCO3 5 h after the first daily meal for 8 weeks. The control group of seven pigs received CaCO3 in the meal. Both groups were given normal P within the meals. Ca and P absorption and retention were evaluated by a 10-day balance trial. Several bones were collected at slaughter to determine bone ash, Ca, and P contents and bending moment (three-point bending test). Ingesting Ca after the meal did not affect Ca bioavailability or phosphorus absorption, but did reduce P retention, which in turn decreased the bone scores. Osteopenia, indicated by decreased total mineral contents of bones (and decreased ash:bone volume ratio), was associated with elevated plasma osteocalcin in the CAA group. Thus, CaCO3 need not be incorporated into a meal for high Ca absorption, provided that Ca is given after a meal, but simultaneous intakes of Ca and P are required for the best mineral retention.
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PMID:Mineral bioavailability and bone mineral contents in pigs given calcium carbonate postprandially. 857 8

For evaluating the long-term effects of the bisphosphonate compound clodronate on the rat skeleton, 100 female rats were given subcutaneous injections of clodronate at doses of 0 (vehicle), 4 (low), or 12 (high) mg/kg per week, or 50 mg/kg every fourth week (cyclical). The treatment was started at 3 months of age and was continued for 6 months. The mechanical strength of bones was studied by torsion of the tibia, three-point bending of the femur, axial compression of the femoral neck, and compression of a lumbar vertebra. Quantitative histomorphometric variables were determined from distal femur and lumbar vertebra, and variables reflecting bone metabolism were measured in serum and urine. Bone mass, indicated by ash weight of the tibia, was increased with the low and high clodronate doses compared with the vehicle. The maximum load in vertebra compression was increased with the low dose of clodronate compared with the vehicle, whereas changes in other variables concerning bone strength were not significant. In bone histomorphometry, clodronate treatment induced more pronounced changes in cancellous bone volume in distal femur than in lumbar vertebra, the differences not being statistically significant between the groups at either site, however. The longitudinal growth rate of the femur, measured by double-fluorochrome labeling for 1 week at the end of the treatment period, was significantly decreased in the high-dose clodronate group compared with the other groups. Serum values for calcium, tartrate-resistant acid phosphatase, and alkaline phosphatase did not differ between the groups. However, serum osteocalcin was significantly lower in the high-dose group compared with the vehicle group. Urinary calcium, hydroxyproline, and hydroxylysylpyridinoline were decreased at all the clodronate doses administered. In conclusion, the beneficial effects of long-term clodronate treatment on bone mass and strength were observed at the lowest dose used. A high dose of clodronate decreased bone growth rate, which was, however, not reflected in the mechanical quality of bone.
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PMID:Long-term effects of clodronate on growing rat bone. 883 14


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