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)

The ability of clodronate to prevent bone loss and weakening of bone strength was studied in adult rats with established osteopenia. Six-month-old female Sprague Dawley rats were randomized into 13 groups. One group was killed at the start of the study, nine groups were ovariectomized (ovx), and three groups sham-operated (sham). After 4 months, the ovx rats were given either clodronate or vehicle subcutaneously (s.c.), once a week for 3 or 6 months, the cumulative doses of both dosing regimens being 36, 84, and 300 mg/kg. Clodronate reduced the increase in bone turnover as evidenced by serum osteocalcin and urinary deoxypyridinoline. Cancellous bone loss was more severe in distal femur than in lumbar vertebral body already at 4 months after ovx. Cortical osteopenia of femoral middiaphysis was significant at 7 and 10 months after operation and was in accordance with the impaired bending strength of the femoral shaft. In the tibia, the bending strength was, by contrast, increased at each timepoint after ovx. In distal femur, higher values of cancellous bone volume (BV/TV) were found after 6 months of clodronate treatment than in ovx/vehicle-treated rats. In lumbar vertebrae, only the lowest dose of clodronate slightly counteracted the ovx-induced further decrease in BV/TV, but reduced, at all dosages, the impairment of lumbar vertebral compression strength. The maximum load of femoral neck did not differ between vehicle-treated ovx and sham groups after clodronate treatment, but clodronate reduced the weakening of femoral shaft. A further increase in the bending strength of the tibia was found after clodronate treatment. There was a positive correlation between bending strength and ash weight in both the tibia and the femur. Histomorphometry further showed that long-term use of clodronate does not impair bone mineralization or affect modeling-dependent bone formation. In conclusion, clodronate treatment clearly slows down the progress of bone loss and prevents further weakening of bone strength in femoral shaft and vertebrae, even though it cannot completely reverse the effects of ovariectomy-induced changes in established osteopenia.
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PMID:Effect of clodronate treatment on established bone loss in ovariectomized rats. 976 45

Studies on calcium nutrition in appropriate large animal models can be directly relevant to humans. We have examined the effect of dietary Ca deficiency on various bone and bone-related variables, including plasma markers, histomorphometry, mineral content and breaking strength in pigs. Three groups of eight 38-d-old female pigs were fed adequate (0.9%; control), low (0.4%; LCa) or very low (0.1%; VLCa) Ca diets for 32 d. Plasma Ca significantly decreased over time only in the VLCa-deficient pigs. The concentrations of the parathyroid hormones (PTH) and calcitriol increased as Ca deficiency developed, and the plasma PTH and calcitriol levels varied inversely with dietary Ca. The total bone ash contents, bending moments, trabecular bone volume and the mineral apposition rate all decreased as the calcium intake decreased. The osteoclast surface areas were greater than those of controls in both Ca-deficient groups, whereas the osteoblast surface areas were greater only in the VLCa group. The plasma osteoblast-related markers (alkaline phosphatase, carboxy-terminal propeptide of type I procollagen and osteocalcin) were either greater or unaffected in the Ca-deficient pigs. The results indicate that deficient bone mineralization combined with an increased bone resorption led to bone loss and fragility. The differences in the changes in bone cells (number and activity) between LCa and VLCa groups might be due to differences (time and extent) of circulating PTH and calcitriol. The defective mineralization in both Ca-depleted groups resulted mainly from the lack of Ca because their osteoblast activity was either maintained or stimulated. The results also underline the progressive sensitivity of pigs to Ca supply and the usefulness of this model.
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PMID:Calcium-regulating hormones, bone mineral content, breaking load and trabecular remodeling are altered in growing pigs fed calcium-deficient diets. 991 98

Vitamin D insufficiency is still a concern in countries where there is no routine food supplementation, such as France. A low vitamin D status is clearly associated with an increased risk of fracture in the elderly, but the long-term consequences of latent vitamin D insufficiency in young people and adults are not known. We fed 26 growing pigs a high calcium diet (1.1%) with a 1000 IU cholecalciferol/kg diet (controls), or without vitamin D (0D) for 4 months. We then analyzed the overall impact of low vitamin D status on osteotropic hormones (calcitriol and immunoreactive parathyroid hormone), plasma markers of bone remodeling (alkaline phosphatase [ALP] activity, carboxyterminal propeptide of type I procollagen [PICP], osteocalcin, hydroxyproline), whole bone parameters (ash content, bending moment), histomorphometry, and the populations of marrow osteoblastic and osteoclastic precursors by ex vivo cultures. The fall in plasma 25-dihydroxyvitamin [25(OH)D] in the 0D pigs indicated severe depletion of their vitamin D stores. However, they remained normocalcemic, were mildly hyperparathyroid after 2 months of vitamin D deprivation, and showed only a slight decrease in plasma calcitriol. The bone mineral content and bending moment of metatarsals decreased and they had increased osteoblastic (+59%, p < 0.05 0D vs. controls) and osteoclastic (+31%, p < 0.1 0D vs. controls) surfaces. This was not paralleled by increased bone turnover, because plasma hydroxyproline and ALP were unchanged and PICP and osteocalcin were decreased. The adherent fraction of bone marrow cells showed a great increase in the number of total stromal colony-forming units (CFU-F; +93%, p < 0.05 0D vs. controls) and in the percent of ALP(+) CFU-F (+58%, p < 0.01 0D vs. controls) in cultures from 0D pigs. More tartrate-resistant acid phosphatase-positive (TRAP(+)) multinucleated cells were generated in cultures of nonadherent marrow cells from 0D pigs, and the area of resorption was 345% greater than in controls. Thus, vitamin D deprivation caused only moderate hormonal changes in growing pigs fed a high-calcium diet, but affected their bone characteristics and greatly enhanced the pool of osteoblasts and osteoclasts by stimulating the commitment of their precursors in bone marrow.
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PMID:In vivo bone metabolism and ex vivo bone marrow osteoprogenitors in vitamin D-deprived pigs. 1077 89

The mechanisms controlling the initiation of mineralization of bone matrix are not clear. To examine this process, we established a cell line called MLO-A5 that mineralizes in sheets, not nodules, within 3 days of culture in the presence of beta-glycerophosphate (beta-GP) and ascorbic acid and within 7 days in the absence of beta-GP and ascorbic acid. The mineral formed in both cases was shown to be bonelike apatite by Fourier transformed infrared (FTIR) spectroscopy. Mineral-to-matrix ratios (min/matrix) calculated from the FTIR data, which are related directly to ash weight, were approximately 0.4 in the absence of beta-GP and ascorbic acid and approximately 1.2 in the presence of beta-GP and ascorbic acid. By comparison, these ratios in fetal rat calvarial cells without beta-GP equal 0 and with beta-GP 1.9. This cell line and three others (MLO-A2, -D1, and -D6) were isolated from the long bones of transgenic mice expressing the large T-antigen driven by the osteocalcin promoter, the same mice from which the osteocyte-like cell line MLO-Y4 was isolated.(1) The cell lines were selected based on a dendritic or stellate morphology. MLO-A5 cells express high alkaline phosphatase, collagen type 1, parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor, bone sialoprotein (BSP), and osteocalcin (767 ng/10(6) cells compared with <1-2.2 ng/10(6) cell for primary mouse osteoblasts and five osteoblast cell lines). The single unique feature of the MLO-A5 cells compared with the other three nonmineralizing cell lines is the high expression of messenger RNA (mRNA) for BSP. These cell lines may represent stages of osteocyte differentiation and the MLO-A5 cells represent the postosteoblast, preosteocyte responsible for triggering mineralization of osteoid.
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PMID:Establishment of an osteoid preosteocyte-like cell MLO-A5 that spontaneously mineralizes in culture. 1154 31

This study was designed to investigate the effect of high-impact and low-repetition jump training on bones in ovariectomized (OVX) rats. Forty female Wistar rats were sham-operated (sham) or OVX at the age of 11 weeks. The rats were divided randomly into the following four groups: sham-sedentary (SS; n = 10), sham-exercised (SE; n = 10), OVX-sedentary (OS; n = 10), and OVX-exercised (OE; n = 10). The rats started the jump training at the age of 12 weeks. The jump-training protocol was 10 times/day, 5 days/week and the jumping-height was 40 cm. After 8 weeks of training, the mass and breaking force in the tibia and ulna, cross-sectional areas of diaphysis in the tibia, and serum bone turnover markers were measured. The jump training significantly increased the fat-free dry weight, ash weight, and ultimate breaking force in the tibia. The rate of increase in these parameters was similar in both the sham and the OVX groups. On the other hand, in the ulna, there were no significant changes in the ultimate breaking force. The jump training significantly increased the periosteal perimeter and cortical area, although the increase in these parameters in OE compared with OS was lower than that in SE compared with SS. The jump training significantly increased serum osteocalcin in the OVX groups, as well as in the sham groups. These results suggest that high-impact and low-repetition training had beneficial effects on bone formation and bone biomechanical properties in OVX rats, as well as in sham rats.
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PMID:Effect of high-impact and low-repetition training on bones in ovariectomized rats. 1154 39

An experiment was conducted to determine long-term effects of dietary boron (B) on reproductive and bone characteristics in gilts. Weanling gilts (n = 50) were allotted to 10 pens based on weaning weight and litter origin. Pens were randomly assigned to receive one of two dietary treatments that consisted of a basal diet low in B (control) and the basal diet supplemented with 5 mg of B/kg diet as sodium borate. Gilts remained on their respective experimental diets throughout the nursery phase, growing-finishing phase, sexual maturity, breeding, gestation, and lactation. The day of first observed standing estrus was defined as puberty, and each pubertal gilt was bred via AI at the second observed standing estrus. Eight randomly selected gilts per treatment were slaughtered at d 35 of gestation for the assessment of embryonic and reproductive characteristics, bone characteristics, and tissue B concentrations. The remaining pregnant gilts (control, n = 11; 5 mg supplemental B/kg diet, n = 10) farrowed, and litter characteristics at farrowing and weaning were determined. Age at puberty was not affected (P = 0.72) by B, and neither were the number of corpora lutea on the ovaries (P = 0.44) or the total number of embryos (P = 0.95) at d 35 of gestation. Boron supplementation increased (P = 0.05) pig weaning weight and tended (P = 0.11) to increase pig birth weight; however, no other litter characteristics were affected (P > 0.12) by B. Extrinsic and intrinsic strength measures of bone were increased (P < 0.09) by B. Fat-free bone ash percentage and bone mineral concentrations were not affected (P > or = 0.19) by dietary B. Supplemental B increased (P < or = 0.06) the B concentrations of the muscle, liver, and reproductive tissues. Serum osteocalcin concentrations tended (P = 0.13) to be increased by dietary B, which may be related to increased bone turnover in B-supplemented gilts. Results indicate that B may have beneficial effects upon reproductive and bone characteristics.
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PMID:Long-term effects of boron supplementation on reproductive characteristics and bone mechanical properties in gilts. 1183 13

PTH has anabolic and catabolic actions in bone that are not clearly understood. The protooncogene c-fos and other activating protein 1 family members are critical transcriptional mediators in bone, and c-fos is up-regulated by PTH. The purpose of this study was to examine the mechanisms of PTH and the role of c-fos in PTH-mediated anabolic actions in bone. Mice with ablation of c-fos (-/-) and their wild-type (+/+) and heterozygous (+/-) littermates were administered PTH for 17 d. The +/+ mice had increased femoral bone mineral density (BMD), whereas -/- mice had reduced BMD after PTH treatment. PTH increased the ash weight of +/+ and +/-, but not -/-, femurs and decreased the calcium content of -/-, but not +/+ or +/-, femurs. Histomorphometric analysis showed that PTH increased trabecular bone volume in c-fos +/+, +/- vertebrae, but, in contrast, decreased trabecular bone in -/- vertebrae. Serum calcium levels in +/+ mice were greater than those in -/- mice, and PTH increased calcium in -/- mice. Histologically, PTH resulted in an exacerbation of the already widened growth plate and zone of hypertrophic chondrocytes but not the proliferating zone in -/- mice. PTH also increased calvarial thickness in +/+ mice, but not -/- mice. The c-fos -/- mice had lower bone sialoprotein and osteocalcin (OCN), but unaltered PTH-1 receptor mRNA expression in calvaria, suggesting an alteration in extracellular matrix. Acute PTH injection (8 h) resulted in a decrease in osteocalcin mRNA expression in wild-type, but unaltered expression in -/-, calvaria. These data indicate that c-fos plays a critical role in the anabolic actions of PTH during endochondral bone growth.
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PMID:Anabolic actions of parathyroid hormone during bone growth are dependent on c-fos. 1223 15

Hypertension has been associated with abnormalities of Ca and bone metabolism. Consequently, dietary strategies aimed at reducing blood pressure may also benefit bone health; however, this issue has received little attention. Therefore, the objective of the present study was to investigate the effect of two antihypertensive-type diets on blood pressure and bone metabolism and composition in normotensive (Wistar-Kyoto NHsd, WKY) and hypertensive (spontaneously hypertensive NHsd, SHR) rats. Thirty WKY and thirty SHR male rats, 14 weeks old, were separately randomized by weight into three groups of ten rats each. One group from each strain was given a control diet while the other two groups were fed two anti-hypertensive (high fruit and vegetable (F/V) and high fruit and vegetable and low-fat dairy produce (combination)) diets for 8 weeks. SHR rats were significantly (P<0.01) heavier than WKY rats. Blood pressure and femoral length, width, dry weight, ash, Ca, Mg, P and bone mineral mass were significantly (P<0.0001) greater in SHR than WKY rats, but were unaffected by diet, irrespective of strain. While markers of bone formation (serum osteocalcin) and bone resorption (urinary pyridinoline and deoxypyridinoline) were similar in both strains, these markers were significantly (P<0.05) lower (28-31, 16-23, 31-33 % respectively) in the SHR rats fed the combination diet relative to those fed the control and F/V diets. Bone turnover in WKY rats was unaffected by diet. In conclusion, these findings suggest that the combination diet may benefit bone metabolism in hypertensive animals. However, as blood pressure was unaffected by this diet, the mechanism by which it reduced bone turnover requires further investigation.
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PMID:The effect of nutrient profiles of the Dietary Approaches to Stop Hypertension (DASH) diets on blood pressure and bone metabolism and composition in normotensive and hypertensive rats. 1272 May 95

This study was conducted to evaluate the effects of dietary vitamin K (menadione) on bone quality in cage-raised broilers. Three hundred and sixty male broilers were randomly allotted to one of six treatments, with six replicate pens per treatment and 10 chicks per pen. Broilers were fed one of six diets including a control diet or the control diet plus graded levels of vitamin K (0.5 mg/kg, 2 mg/kg, 8 mg/kg, 32 mg/kg and 128 mg/kg). Water and feed were provided ad libitum during the 7-week experimental period. Results indicated that vitamin K supplementation of broilers diets significantly effected bone quality and feed efficiency. The treatment containing vitamin K at 8 mg/kg improved growth performance (during weeks 6-7) and bone quality (during weeks 0-3). In our study, hydroxyapatite binding capacity of serum osteocalcin (during weeks 0-3), bone breaking strength, bone flexibility, bone ash weight increased linearly (P < 0.05) and bone mineral density, bone mineral content increased quadratically (P < 0.05) with increasing supplementation of vitamin K. In conclusion, to gain optimum bone quality and broiler performance, our studies suggest that the concentration of vitamin K in broilers diets should be 8 mg/kg, 2 mg/kg, and 2 mg/kg, for the starter, grower and finisher phases, respectively. Furthermore, it was shown that the starter period is an important phase for improving bone quality. In addition, this study validated the mechanism of vitamin K effects on bone quality. Vitamin K boosts the carboxylation of osteocalcin and decreases the concentration of serum under-carboxylated osteocalcin enhancing hydroxyapatite binding capacity of serum osteocalcin and improving bone quality.
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PMID:Effects of dietary vitamin K levels on bone quality in broilers. 1290 64

We have reported that transgenic mice overexpressing human osteoblast stimulating factor-1 (osf1) under the control of the human osteocalcin promoter have a significantly higher bone mineral content and density than nontransgenic littermates. Consequently, bone mass loss due to estrogen deficiency was compensated for in ovariectomized female mice. Here, we show that in this transgenic line, the bone mass increase was evident in female, but not male, mice, as evaluated using the ash assay, double-emission X-ray analysis, and calcein double-labeling to determine the bone formation rate. To elucidate a possible influence on gene expression, we analyzed genomic structures of the inserted transgene and its flanking regions in mouse chromosomes. The results revealed that the transgene was integrated in the mouse repetitive sequences, 234-bp-long gamma-satellite repeats, as inverted multiple (5 + 8) copies. Twelve copies at most seemed to be functional, but no direct evidence supporting female-specific mRNA synthesis of the transgene was obtained.
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PMID:Bone mass increase specific to the female in a line of transgenic mice overexpressing human osteoblast stimulating factor-1. 1510 72


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