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

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

To assess the relationship between insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within 10 years of menopause were studied. In all subjects, BMD at the lumbar spine and left hip were measured using dual-energy X-ray absorptiometry and blood samples were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were measured. In a subgroup of these subjects serum concentrations of IGF-binding protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of type I procollagen (PICP) were also measured. Serum IGF-I correlated significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p = 0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not with PICP, PTH, or BMD at any site. Although there was a strong correlation between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP) nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone turnover are related, but there is no relationship between IGF-I and BMD.
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PMID:Insulin-like growth factor-I and bone mineral density. 966 25

The impact of spinal cord injury (SCI) on later bone mineral status was studied in 35 adults who had sustained their injury in childhood. The median age of the patients was 31 years, the median age at injury 12.9 years and the median time period from injury was 19 years. The methods used in the study were clinical interview and examination, measurement of bone mineral density (BMD) of the lumbar spine and the proximal femur with dual energy X-ray absorptiometry (DEXA) and estimation of bone turnover with biochemical markers. The densitometric examination revealed that the BMD at the lumbar spine was within the normal range but grossly decreased in the femoral region. Moreover, there was a significant difference in BMD between patients with high (C2-T6) and low (below T6) lesions in the lumbar spine as well as in the femoral region. Patients with lower lesions had higher BMD values. The markers of bone turnover which were studied were serum and urinary calcium and phosphate serum alkaline phosphatase and its isoenzymes, osteocalcin, carboxyterminal propeptide of human type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and urinary deoxypyridinoline. These markers of bone metabolism showed no signs of ongoing accelerated bone formation or resorption. The present study suggests that caution should be observed in weight bearing training or mobilisation of patients with pediatric SCI or perhaps with long standing SCI because of increased fracture risk. The prevention of dissociated osteoporosis should be investigated further in order to avoid fractures of weakened bones. The modes of prevention might be found in the use of modern pharmacotherapy of osteoporosis and from correctly dosage physical training.
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PMID:Bone mineral status after pediatric spinal cord injury. 977 50

This study was undertaken to examine the effects of 12 weeks of skeletal unloading on parameters of calcium homeostasis, calcitropic hormones, bone histology, and biochemical markers of bone turnover in 11 normal subjects (9 men, 2 women; 34 +/- 11 years of age). Following an ambulatory control evaluation, all subjects underwent 12 weeks of bed rest. An additional metabolic evaluation was performed after 12 days of reambulation. Bone mineral density declined at the spine (-2.9%, p = 0.092) and at the hip (-3.8%, p = 0.002 for the trochanter). Bed rest prompted a rapid, sustained, significant increase in urinary calcium and phosphorus as well as a significant increase in serum calcium. Urinary calcium increased from a pre-bed rest value of 5.3 mmol/day to values as high as 73 mmol/day during bed rest. Immunoreactive parathyroid hormone and serum 1,25-dihydroxyvitamin D declined significantly during bed rest, although the mean values remained within normal limits. Significant changes in bone histology included a suppression of osteoblastic surface for cancellous bone (3.1 +/- 1.3% to 1.9 +/- 1.5%, p = 0.0142) and increased bone resorption for both cancellous and cortical bone. Cortical eroded surface increased from 3.5 +/- 1.1% to 7.3 +/- 4.0% (p = 0.018) as did active osteoclastic surface (0.2 +/- 0.3% to 0.7 +/- 0.7%, p = 0.021). Cancellous eroded surface increased from 2.1 +/- 1.1% to 4.7 +/- 2.2% (p = 0.002), while mean active osteoclastic surface doubled (0.2 +/- 0.2% to 0.4 +/- 0.3%, p = 0.020). Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, and type I procollagen extension peptide) did not change significantly during bed rest. Urinary biochemical markers of bone resorption (hydroxyproline, deoxypyridinoline, and N-telopeptide of type I collagen) as well as a serum marker of bone resorption (type I collagen carboxytelopeptide) all demonstrated significant increases during bed rest which declined toward normal during reambulation. Thus, under the conditions of this study, the human skeleton appears to respond to unloading by a rapid and sustained increase in bone resorption and a more subtle decrease in bone formation.
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PMID:The effects of twelve weeks of bed rest on bone histology, biochemical markers of bone turnover, and calcium homeostasis in eleven normal subjects. 978 48

Osteopenia has been ascribed to diabetics without residual insulin secretion and high insulin requirement. However, it is not known if this is partially due to disturbances in the IGF system, which is a key regulator of bone cell function. To address this question, we performed a cross-sectional study measuring serum levels of IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, IGFBP-4 and IGFBP-5 by specific immunoassays in 52 adults with Type 1 (n=27) and Type 2 (n=25) diabetes mellitus and 100 age- and sex-matched healthy blood donors. In the diabetic patients, we further determined serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and several biochemical bone markers, including osteocalcin (OSC), bone alkaline phosphatase (B-ALP), carboxy-terminal propeptide of type I procollagen (PICP), and type I collagen cross-linked carboxy-terminal telopeptide (ICTP). Urinary albumin excretion was ascertained as a marker of diabetic nephropathy. Bone mineral density (BMD) of hip and lumbar spine was determined by dual-energy X-ray absorptiometry. Data are presented as means+/-s.e.m. Differences between the experimental groups were determined by performing a one-way analysis of variance (ANOVA), followed by Newman-Keuls test. Correlations between variables were assessed using univariate linear regression analysis and partial correlation analysis. Type 1 diabetics showed significantly lower IGF-I (119+/-8 ng/ml) and IGFBP-3 (2590+/-104 ng/ml) but higher IGFBP-1 levels (38+/-10 ng/ml) compared with Type 2 patients (170+/-13, 2910+/-118, 11+/-3 respectively; P<0.05) or healthy controls (169+/-5, 4620+/-192, 3.5+/-0.4 respectively; P<0.01). IGFBP-5 levels were markedly lower in both diabetic groups (Type 1, 228+/-9; Type 2, 242+/-11 ng/ml) than in controls (460+/-7 ng/ml,P<0. 01), whereas IGFBP-4 levels were similar in diabetics and controls. IGF-I correlated positively with IGFBP-3 and IGFBP-5 and negatively with IGFBP-1 and IGFBP-4 in all subjects. Type 1 patients showed a lower BMD of hip (83+/-2 %, Z-score) and lumbar spine (93+/-2 %) than Type 2 diabetics (93+/-5 %, 101+/-5 % respectively), reaching significance in the female subgroups (P<0.05). In Type 1 patients, BMD of hip correlated negatively with IGFBP-1 (r=-0.34, P<0.05) and IGFBP-4 (r=-0.3, P<0.05) but positively with IGFBP-5 (r=0.37, P<0. 05), which was independent of age, diabetes duration, height, weight and body mass index, as assessed by partial correlation analysis. Furthermore, biochemical markers indicating bone loss (ICTP) and increased bone turnover (PTH, OSC) correlated positively with IGFBP-1 and IGFBP-4 but negatively with IGF-I, IGFBP-3 and IGFBP-5, while the opposite was observed with bone formation markers (PICP, B-ALP) and vitamin D3 metabolites. In 20 Type 2 patients in whom immunoreactive proinsulin could be detected, significant positive correlations were found between proinsulin and BMD of hip (r=0.63, P<0.005), IGF-I (r=0.59, P<0.01) as well as IGFBP-3 (r=0.49, P<0.05). Type 1 and Type 2 patients with macroalbuminuria showed a lower BMD of hip, lower IGFBP-5 but higher IGFBP-4 levels, suggesting that diabetic nephropathy may contribute to bone loss by a disturbed IGF system. In conclusion, the findings of this study support the hypothesis that the imbalance between individual IGF system components and the lack of endogenous proinsulin may contribute to the lower BMD in Type 1 diabetics.
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PMID:Serum levels of insulin-like growth factor system components and relationship to bone metabolism in Type 1 and Type 2 diabetes mellitus patients. 979 71

The purpose of this study was to characterize the molecular expression of a spontaneously immortalized and cloned cell line (MDPC-23) derived from 18-19 day CD-I fetal mouse molar dental papillae to determine if these cells were odontoblast-like. Western blots showed that a protein band, at approximately 105 kDa, reacting positively with anti-DSP antibodies and co-migrating with mouse DSP, was present in lysates of cells from passages 7, 37 and 77, in serum-free conditioned medium from passage 37 cells, and in mouse dentin extract. A minor band at 55 kDa was also apparent in cell lysates. Using a cDNA probe for a 486bp mouse DSP coding sequence, DSP or DSP-PP mRNA expression was detected by Northern analysis as well as Southern analysis after RT-PCR in all three passages. It was also shown that in these cells 1,25 (OH)2 vitamin D3 upregulated both osteopontin and osteocalcin mRNA, and dexamethasone downregulated alkaline phosphatase and alpha2(I) collagen mRNA. Thus, MDPC-23 cells express proteins which are common to mineralizing tissue. The expression of DSP and DSP-PP strongly suggests that this cell line is from the odontoblast lineage.
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PMID:Expression of dentin sialoprotein (DSP) and other molecular determinants by a new cell line from dental papillae, MDPC-23. 986 25

A 69-year-old Japanese woman was referred to our hospital because of abnormal skull X-ray findings. Serum total alkaline phosphatase, bone-specific alkaline phosphatase 3, osteocalcin and propeptide carboxyterminal of type I procollagen (PICP) levels were markedly elevated. Urinary excretion of hydroxyproline was also increased, suggesting that both bone formation and resorption were accelerated. Radiography of the skull showed "cotton wool" appearance. T1-enhanced MRI revealed that the skull-cap and diploe were swelled up. In 99mTc-MDP bone scintigraphy, all areas of the skull and a part of the right hemipelvis showed high uptake of the radioisotope. Based on the findings we made diagnosis of Paget's disease of bone which is a rare bone disorder in Japanese. Three-month oral administration of etidronate disodium resulted in normalization of serum PICP levels and urinary hydroxyproline excretion, whereas alkaline phosphatase levels were only partially lowered. Levels of the markers of bone turnover remained normal during a follow-up period of 3 months after the discontinuation of the treatment.
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PMID:A patient with Paget's disease of bone treated with etidronate disodium. 991 22

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

Previous studies have shown that treatment with estrogen or calcium decreases bone turnover in older women. The mechanisms by which estrogen and calcium exert their effects are probably different. We therefore examined the possibility of an additive or synergistic effect of combined treatment with calcium and low dose estrogen on bone turnover in older women, using biochemical markers. Thirty-one healthy women over 70 yr of age were randomized to 12 weeks of treatment with either micronized 17beta-estradiol [0.5 mg/day Estrace (E2)] or 1500 mg/day elemental calcium, given as carbonate plus vitamin D (800 IU/day; Ca+D). At the end of the initial 12-week treatment period, both groups received both Ca+D and E2 for an additional 12 weeks. Eleven older women were followed for 36 weeks without any treatment and served as a control group. Serum and urine were collected at baseline, at 12 and 24 weeks on treatment, and at 12 weeks after treatment was terminated for measurement of biochemical markers of bone turnover. Markers of bone formation were bone alkaline phosphatase, osteocalcin, and type I procollagen peptide; markers of bone resorption were urinary cross-linked C-telopeptides and N-telopeptides of type I collagen, serum cross-linked N-telopeptides of type I collagen, urinary free deoxypyridinoline cross-links, and serum bone sialoprotein. Repeated measures ANOVA was used to determine changes in bone turnover measures over time by group. All markers of bone resorption decreased with initial treatment and decreased further with combination therapy (P < 0.001). Markers of bone formation decreased with Ca+D treatment, but not with E2 alone; there was no additional effect of combination therapy on formation markers compared to Ca+D alone. Neither markers of formation nor resorption changed in the control group. These results suggest that there is an additive effect of low dose estrogen and calcium on bone resorption, but not on bone formation, in older women. Thus, the combination of low dose estrogen plus calcium is likely to be more effective in older women than either treatment alone.
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PMID:Low dose estrogen and calcium have an additive effect on bone resorption in older women. 992 80

To test the hypothesis that bone sensitivity to estrogens differ with the pubertal status, we cultured human osteoblasts (hOBs) from 14 girls (3-18 years) and examined the effects of repeated weekly doses of 17beta-estradiol (E2, 10 pM-10 nM) on estradiol receptor (ER) and progesterone receptor (PR) expression, type I procollagen (PICP) and osteocalcin (BGP; bone Gla protein) production, and alkaline phosphatase (ALP) activity. The bone samples were divided into two equal groups according to the pubertal status and plasma E2 level of the donor. The two groups were significantly different for age (9 +/- 1 and 15 +/- 1 years), pubertal status (Tanner stages I-III and IV-V), and plasma E2 concentrations (17 +/- 3 and 49 +/- 4 pg/ml). ER and PR were expressed and not influenced by the sexual maturation in untreated cells. E2 increased ER in the two groups with nanomolar doses. Picomolar doses did not significantly increase ER expression but led to significant differences in the percentage of cells expressing ER in premenarchial (33%) and postmenarchial (7%) hOB cultures. In the two groups, E2 had no clear effect on PR expression, ALP activity, nor BGP production. But repeated weekly doses of E2 significantly influenced PICP production at picomolar doses. This effect depended upon the sexual maturation of the donor. E2 decreased PICP in premenarchial cultures and increased PICP in postmenarchial cultures. Thus, E2 modulates in vitro human bone cell metabolism and probably their phenotype and has different effects, depending on the pubertal status of the donor. Unlike what could have been expected, prepubertal and early pubertal hOBs appear to be specifically sensitive to picomolar doses of E2, suggesting that this hormone is a crucial regulator of bone metabolism even before puberty.
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PMID:In vitro responses to 17beta-estradiol throughout pubertal maturation in female human bone cells. 1002 2

Age-related bone loss may be a consequence of a lack of osteoblastic formation and/or function. In vitro, the osteoblastic response to 1,25(OH)2D3, an important regulator of osteoblastic function, appears to depend on the stage of osteoblastic maturation. In this study, we examined the response to 1,25(OH)2D3 of C-terminal type I procollagen (PICP), alkaline phosphatase (ALP), and osteocalcin (OC) secretion in primary cultures of osteoblastic cells from human trabecular bone (hOB). Forty-four bone samples were obtained from subjects undergoing knee arthroplastia, 20 aged 50-70 (64 +/- 5), and 24 >70 (73 +/- 2) years. Another 33 bone samples were obtained from subjects undergoing hip arthroplastia, 21 were aged 50-70 (64 +/- 4) and 12 >70 (75 +/- 5) years. Pooling knee and hip hOB cell cultures, we found that PICP secretion decreased after 1,25(OH)2D3 in hOB cells from the older group (>70 years). Treatment with 1,25(OH)2D3 increased ALP secretion in these cells only in the younger group (50-70 years), whereas it increased OC secretion in hOB cells in both age groups. By pooling hOB cell cultures from both age groups we found that knee hOB cells increased OC secretion, and decreased PICP secretion, after 1,25(OH)2D3. This metabolite also increased OC secretion in hip hOB cells. Considering the influence of donor age at the same skeletal site, 1,25(OH)2D3 was found to stimulate ALP secretion only in knee hOB cells in the younger group. In contrast, this metabolite decreased ALP secretion in hip hOB cells in the older group. PICP secretion decreased after 1,25(OH)2D3 only in hOB cells in the older group, at both skeletal sites. In age-matched cultures, OC secretion was lower in hip hOB cells compared with those from the knee in the older group, but was similar in these cell cultures from both skeletal sites in the younger group. OC secretion after 1,25(OH)2D3 stimulation did not show age differences in knee hOB cells, but was lower in hip hOB in the older group. In summary, our results demonstrate that the response of various osteoblastic markers to 1,25(OH)2D3 in primary cultures of hOB cells depends on the donor age and skeletal site of origin.
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PMID:Influence of skeletal site of origin and donor age on 1,25(OH)2D3-induced response of various osteoblastic markers in human osteoblastic cells. 1007 12


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