Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human osteoblasts express a repertoire of cadherins, including N-cadherin (N-cad), cadherin-11 (C11), and cadherin-4 (C4). We have previously shown that direct cell-cell adhesion via cadherins is critical for BMP-2-induced osteoblast differentiation. In this study, we have analyzed the regulation of cadherin expression in normal human trabecular bone osteoblasts (HOB), and osteoprogenitor marrow stromal cells (BMC), during exposure to dexamethasone, another inducer of human bone cell differentiation. Dexamethasone inhibited the expression of both C11 and N-cad mRNA in both BMC and HOB, although the effect was much more pronounced on N-cad than on C11. This action of the steroid was dose dependent, was maximal at 10(-7) M concentration, and occurred as early as after 1 day of incubation. By contrast, expression of C4 mRNA and protein was strongly induced by dexamethasone in BMC and was stimulated in HOB. This stimulatory effect lasted for at least 2 weeks of incubation. A cadherin inhibitor, HAV-containing decapeptide only partially ( approximately 50%) prevented dexamethasone-induced stimulation of alkaline phosphatase activity by BMC, which instead was not altered by incubation with a neutralizing antibody against C4. Therefore, the pattern of cadherin regulation by dexamethasone radically differs form that observed with BMP-2. Dexamethasone effects on certain osteoblast differentiated features, such as induction of alkaline phosphatase activity are not strictly dependent on cadherin function.
...
PMID:Differential regulation of cadherins by dexamethasone in human osteoblastic cells. 1076 Sep 57

Generally, the incidence of osteoporotic fracture is lower in black populations and in men. These effects of ethnicity and gender may result from differences in peak bone mineral density (PBMD) and bone turnover (BT), which in turn are affected by bone size. Therefore, the aims of this study were to examine the effects of ethnicity and gender on bone mineral density (BMD) and BT in young African-Caribbean and Caucasian adults, and to adjust for the effect of bone size on BMD and BT. BMD was measured at the lumbar spine, L2-L4 (LS), total body (TB) and femoral neck (FN) by dual-energy X-ray absorptiometry in 44 blacks (16 men, 28 women) and 59 whites (28 men, 31 women) ages 20-37 years. We measured serum bone-specific alkaline phosphatase (BAP) and serum osteocalcin (OC) as markers of bone formation and urinary immunoreactive free deoxypyridinoline (ifDpd) and crosslinked N-telopeptide of type I collagen (NTx) as markers of bone resorption. To adjust the data for any differences in bone size, we calculated: (a) bone mineral apparent density (BMAD), an estimated volumetric bone density which attempts to normalize BMD measurements for bone size; and (b) bone resorption markers as a ratio to total body bone mineral content (TB BMC). Two-way analysis of variance was used to compare the effects of race and gender, and to test for any interaction between these two factors. Blacks had higher BMD compared with whites at the TB (p<0.001), LS (p = 0.0001) and FN (p = 0.0005). This increase remained significant at the LS only after calculating BMAD. Men had higher BMD at all sites (except at the LS). This increase was no longer significant at the FN after calculating BMAD, and LS BMAD was actually greater in women (p<0.0001). Blacks and whites had similar concentrations of turnover markers, but men had higher bone turnover markers than women (BAP, p<0.0001; OC, p = 0.002; ifDpd, p = 0.03; NTx, p < 0.0001). This increase in bone resorption markers was no longer significant after adjusting for TB BMC (except for NTx in whites). We conclude that the skeletal advantage in blacks during young adulthood is not explained by bone size. However, it seems probable that bone size effects partially explain gender differences in BMD and bone turnover.
...
PMID:Ethnic and gender differences in bone mineral density and bone turnover in young adults: effect of bone size. 1098 67

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.
...
PMID:Effect of melatonin on bone metabolism in ovariectomized rats. 1181

The purpose of this study was to examine if substantial bone loss occurs in weaned pigs by feeding a phosphorus-deficient diet with or without fumaric acid. Eighteen weaned pigs were used. The animals were assigned to three groups: group C (control; 0.65% P on DM basis), group LP (low phosphorus; 0.37% P on DM basis) and group LPF (low phosphorus plus fumaric acid; 0.35% P on DM basis plus 2% fumaric acid). These three diets were fed to the groups for a period of four weeks after a two-week adaptation period. Blood samples were collected once a week. Carboxyterminal telopeptide of type I collagen (ICTP) in serum was used as a bone resorption marker. Osteocalcin (OC) and bone-specific alkaline phosphatase (bAP) were used as bone formation markers. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography. BAP activities significantly increased (24%) in group LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. In contrast, ICTP concentrations significantly increased with time in group LP and LPF, and at the last sampling day group LPF had significantly increased activities in comparison to group C. BMD and BMC in femur and tibia significantly decreased in group LP and LPF. The results show that P-deficient diets induce a bone loss. Fumaric acid did not influence the degree of bone loss. With a better understanding of its effect on bone, dietary phosphorus requirements in pigs could be more precisely defined.
...
PMID:Influence of dietary phosphorus deficiency with or without addition of fumaric acid to a diet in pigs on bone parameters. 1190 68

Most women with Turner syndrome (TS) have no gonadal activity and thus lack estrogen. Bone mineral density (BMD) is often reduced, leading to an increased risk of osteoporosis and fractures. However, growth retardation with reduced final height and other endocrine disturbances may compromise interpretation of skeletal measurements. The aim of the present study was to explore skeletal findings, bone metabolism, and calcium homeostasis in TS. Sixty women with TS (age, 37 +/- 9 yr) and 181 normal age-matched female controls were studied. Bone area (A; square centimeters), bone mineral content (BMC; grams), area-adjusted BMD (aBMD; grams/square centimeter), and volumetric BMD (vBMD; grams/cubic centimeter) were measured at lumbar spine, femoral neck, and forearm using dual energy x-ray absorptiometry. Twenty-eight percent had osteopenia, and 23% had osteoporosis, according to World Health Organization criteria. At the lumbar spine, A, BMC, aBMD, and vBMD were reduced by 18, 27, 11, and 6%, respectively; at the femoral neck, A, BMC, and aBMD were reduced by 2, 10, and 8%, respectively, whereas the 9% reduction in vBMD was insignificant (P = 0.07); and in the forearm, A, BMC, and aBMD were reduced by 53, 55, and 9%, respectively. Bone markers indicated an enhanced bone resorption (21 and 23% increase in C-terminal and N-terminal cross-linking telopeptides of type I collagen/creatinine, respectively) with unchanged (osteocalcin, procollagen I N-terminal propeptide) or reduced (54% reduction in bone alkaline phosphatase) bone formation. Plasma levels of calcium and 25-hydroxyvitamin D (26%) were reduced, and PTH levels increased (74%) in TS. IGF-I (30%), IGF binding protein 3 (18%), testosterone (50%), and SHBG (40%) were reduced in TS. In summary, A, BMC, and aBMD were found to be universally reduced in TS, whereas vBMD was slightly reduced in the spine. Increased resorption of bone was present, with normal or blunted bone formation, suggesting uncoupling or imbalance in bone remodeling. Skeletal changes may be induced by chromosome abnormalities or by secondary endocrine or metabolic changes related to a relative estrogen deficiency, testosterone deficiency, reduced IGF-I, low vitamin D status, and secondary hyperparathyroidism.
...
PMID:Marked disproportionality in bone size and mineral, and distinct abnormalities in bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional study. 1205 Feb 53

This study was conducted to examine if substantial bone loss occurs in growing pigs fed a vegetarian diet in comparison with a diet containing fishmeal. Twelve 6-week-old weaned pigs were assigned to two groups: group V [vegetarian diet; 0.61% phosphorus (P) in dry matter until 25 kg and 0.46% P until the end of the experiment] and group F (fishmeal diet; 0.61% P in dry matter until 25 kg and 0.46% P until the end of the experiment). Phytase was added to both diets. These two diets were fed to the two groups for a period of 6 weeks. Blood samples were collected weekly, faeces were collected three times a week. Concentrations of osteocalcin (OC) and carboxyterminal telopeptide of type I collagen (ICTP) were measured in serum, using a radioimmunoassay, and bone-specific alkaline phosphatase (bAP) was measured using an enzyme immunoassay. Bone mineral density (BMD) and content (BMC) were determined by peripheral quantitative computer tomography (pQCT) in the tibia and phalanx. In addition, 1,25-dihydroxyvitamin D (VitD) and parathyroid hormone (PTH) were measured in serum. The digestibility of P was significantly decreased in group V. Significant changes in bAP activities and OC concentrations occurred with time during the 6 weeks. ICTP concentrations were significantly higher in group V. Total BMC and BMD in the tibia and BMD in the phalanx significantly decreased in group V. The results show that a vegetarian diet induces a significant loss of bone and a higher bone formation in group V compared with group F, although phytase was added to both diets. The dietary requirements for P in pigs, especially in the context of feeding vegetarian diets and adding an appropriate amount of phytase, should be investigated further.
...
PMID:Influence of a vegetarian diet versus a diet with fishmeal on bone in growing pigs. 1212 36

Chemical mutagenesis followed by screening for abnormal phenotypes in the mouse holds much promise as a method for revealing gene function. We describe a mouse N-ethyl-N-nitrosourea (ENU) mutagenesis program incorporating a genomewide screen of dominant as well as recessive mutations affecting musculoskeletal disorders in C3H/HeJ mice. In a primary screen, progeny of one-generation dominant mutations (F(1)) and three-generation recessive (F(3)) mutations were screened at 10 weeks of age for musculoskeletal disorders using dual-energy X-ray absorptiometery (DEXA) and biochemical markers affecting bone metabolism, such as osteocalcin, type I collagen breakdown product, skeletal alkaline phosphatase, and insulin-like growth factor I (IGF-I). Abnormal phenotypes were identified as +/-3SD units different from baseline data collected from age- and sex-matched nonmutagenized control mice. A secondary screen at 16 weeks of age, which included peripheral quantitative computed tomography (pQCT) in addition to those parameters described in our primary screen, was used to confirm the abnormal phenotypes observed in the primary screen. The phenodeviant or outlier mice were progeny tested to determine whether their abnormality segregates bimodally in their offspring with the expected 1:1 or 1:3 Mendelian ratio, in dominant and recessive screens, respectively. With the above screening strategy, we were able to identify several mice with quantitative abnormalities in BMD, BMC, bone size, and bone metabolism. We have progeny tested and confirmed four outliers with low BMD, low bone size, and growth-related abnormality. Our results indicate that the magnitude of change in quantitative phenotypes in the ENU-mutagenized progeny was between 10 and 15%, and hence, the yield of outliers was dependent on the precision of the methods. So far, this ENU mutagenesis program has identified four outliers that can undergo positional cloning.
...
PMID:A genomewide screening of N-ethyl-N-nitrosourea-mutagenized mice for musculoskeletal phenotypes. 1449 51

Bone metabolism in humans and several animal species can be monitored in vivo by measuring enzymes and other protein products released by osteoblasts and osteoclasts, respectively. Bone mineral density (BMD) and content (BMC) can be determined by peripheral quantitative computer tomography (pQCT). Another approach is to measure histomorphometric indices of bone biopsies. The biochemical markers of bone formation currently in use include bone isoenzyme of alkaline phosphatase, osteocalcin and propeptides derived from the N or C terminal ends of the type I procollagen molecule. The longest established method for the measurement of bone resorption is hydroxyproline in urine. However, it is not specific for bone, since it is found in all collagen types and it can also derive from the diet. The most useful markers of bone resorption are breakdown products of type I collagen. The measurement of collagen crosslinks, deoxypyridinoline and pyridinoline, is comparatively more specific to monitor bone resorption. Deoxypyridinoline and pyridinoline are of use in human medicine in the diagnosis and evaluation of bone diseases and in the prediction of the occurrence of fractures and the rates of bone loss. The carboxyterminal telopeptide of type I collagen, which has been used in several animal species, is also a promising bone resorption marker. This overview gives a general idea about the use of different bone markers and measurements of other bone parameters in ruminants during growth, gestation and lactation in relation to calcium metabolism.
...
PMID:Possibilities of monitoring bone metabolism in ruminants--an overview of the methods in use. 1462 92

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.
...
PMID:IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes. 1884 35

In both sexes, a reduction in sex steroid production with aging impairs the musculoskeletal system. The goal of our study was to test the ability of WH-9062, a novel non-steroidal small molecule inhibitor of the 17beta-Hydroxysteroid Dehydrogenase type 2 enzyme, to maintain or improve bone strength without raising serum levels of testosterone or estradiol. Mature, female cynomolgus monkeys with sealed growth plates were allocated into six groups: Sham controls, OVX controls, OVX+Premarin (15 mg/kg/d), and three groups of OVX monkeys receiving WH-9062 at 1, 5 and 25 mg/kg/day. All treatments were administered by daily oral dosing for 23 weeks. Changes in lipid profile caused by OVX were corrected with WH-9062 and included lowering total of cholesterol and non-HDL cholesterol, and maintenance of initial plasma levels of HDL cholesterol. Only the highest dose of WH-9062 lowered bone resorption relative to OVX controls. Elevated bone specific alkaline phosphatase, osteocalcin, BMC and dynamic bone histomorphometry data resulted in desirable bone balance and bone strength. The obtained results support our theory that inhibition of 17beta-HSD type 2 resulted in high local estrogen and/or testosterone levels leading to maintenance of bone formation and bone strength. Collectively, our data demonstrated that the treatment paradigm that utilizes tissue selectivity and receptor bioavailability in conversion of inactive hormones to active forms could be achieved and could result in desirable effects on target tissues such as bone and muscles.
...
PMID:Effect of 17beta-hydroxysteroid dehydrogenase type 2 inhibitor on bone strength in ovariectomized cynomolgus monkeys. 1879 60


<< Previous 1 2 3 4 Next >>

---