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)

We examined the long-term effects of intranasal administration of salmon calcitonin on bone and calcium metabolism in women with established osteoporosis (forearm fracture). Over a period of 5 years, 14 women received discontinuous calcitonin (200 IU) plus calcium (500 mg) daily for 3 years or 4 years. To allow assessment of the optimum duration of therapy, patients in whom treatment had been for shorter intervals were also included. At the end of the first 2 years, a group receiving placebo had lost significantly more bone from their spines and forearms than the group receiving calcitonin in the first year (P less than 0.01). In the 14 women who completed a further 3 years on calcitonin, the bone mineral contents of the spines increased continually. Bone loss in the forearm was arrested for 1 year. Treatment lasting for about 2 years prevented bone loss in both areas. Treatment for 3 years resulted in net gains in spinal bone but no further benefits in relation to forearms. Biochemical parameters of bone turnover (serum alkaline phosphatase levels, plasma bone Gla protein levels, and fasting urinary hydroxyproline/creatinine levels) exhibited similar declines irrespective of the duration of treatment. It is concluded that long-term intranasal treatment with calcitonin produced net gains in spinal bone and that optimum response in forearms was achieved using discontinuous therapy. The ratio between periods with and without treatment was between 1:2 and 2:3.
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PMID:Long-term treatment of established osteoporosis with intranasal calcitonin. 193 1

Eleven Nigerian children with clinically and radiologically proven rickets were assessed biochemically. The children had low or low normal concentrations of total and corrected calcium, and elevated plasma alkaline phosphatase (ALP) activity, but normal plasma phosphate concentrations. Their serum 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations were not significantly different from those in controls, but the ratio of 1,25-(OH)2D to 25-OHD was significantly greater than that in controls. Parathyroid hormone (PTH) concentrations were greater in rachitic children, and there was a significant correlation between 1,25-(OH)2D and PTH concentrations. Osteocalcin concentrations in rachitic children were not significantly different from those in controls, but they were markedly elevated in the three patients with the highest 1,25-(OH)2D and PTH concentrations. One child, from whom a sample of bone (from a corrective osteotomy) was available for histological examination, showed markedly thickened osteoid seams, characteristic of rickets. All the rachitic children had a calcium intake of less than 150 mg daily. Treatment of these rachitic children with calcium gluconate (1 g/d) led to clinical, radiological, and biochemical healing of rickets. We conclude that rickets in Nigerian children is not due to vitamin D deficiency, but to a lack of calcium. This observation has implications regarding the pathogenesis, treatment, and prevention of rickets/osteomalacia in Nigeria and possibly other African and tropical countries.
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PMID:Rickets in Nigerian children: a consequence of calcium malnutrition. 198 79

Osteoblast-like cells are commonly found in the vicinity of osteoclasts formed in long-term human bone marrow cultures, and they are believed to be derived from osteogenic cell precursors belonging to the stromal cell system. This paper describes a new culture method for human osteoblasts from the adherent cell population of long-term human mononuclear bone marrow cultures. The cells obtained exhibited all the classic characteristics of osteoblasts. They contained high intracellular concentrations of alkaline phosphatase and they secreted the osteoblast-specific marker bone Gla protein. Collagen production was mainly (95-98%) procollagen type I propeptide and only minute quantities of procollagen type III propeptide were detectable by radioimmunoassay in the conditioned medium. After eight weeks the cells formed a mineralized matrix on exposure to beta-glycerophosphate and ascorbic acid. This system provides a model for the study of osteoblast differentiation in vitro and may form the basis for the use of defined media in bone cell cultures due to the presence of high concentrations of osteoblast precursors.
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PMID:Formation of osteoblast-like cells from human mononuclear bone marrow cultures. 201 40

Osteoporosis is one of the most common complications of streak gonad syndrome (SGS), however its pathogenesis is still unclear. Bone Gla protein (BGP) has been found to be a serum marker of bone turnover in various metabolic disease states. In the present study serum BGP and alkaline phosphatase (AP) were measured in 13 osteoporotic patients with SGS and in 56 healthy women. Mean (+/- SD) serum BGP levels were normal (7.5 +/- 2.0 ng/ml) in seven patients who had been on estrogen-progestin replacement therapy and became significantly elevated (P less than 0.001) 2 and 3 months after discontinuation of the treatment (15.3 +/- 2.3 and 13.2 +/- 1.0 ng/ml, respectively). Mean (+/- SD) serum AP (207 +/- 65 U/l) showed significant increases (P less than 0.05) 2 months after withdrawal of hormonal substitution (287 +/- 74 U/l). Mean (+/- SD) serum BGP (15.4 +/- 3.5) and AP (287 +/- 49) levels were significantly higher (P less than 0.001 and less than 0.05, respectively) in six patients with SGS who had not been on hormonal substitution. These findings are consistent with those obtained in postmenopausal women suffering from "high remodelling osteoporosis" and suggest that bone turnover in osteoporotic patients with SGS is increased and the skeletal loss is a consequence of accelerated bone loss rather than decreased bone formation.
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PMID:Serum bone Gla protein in streak gonad syndrome. 207 Feb 73

Serum levels of osteocalcin [OC; bone Gla protein (BGP)] and bone alkaline phosphatase (B-AP) are both correlated to osteoblastic activity, which may be regulated by several hormones, including estrogen, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and PTH. Estrogen shows reproducible variations during the menstrual cycle, while available data on variations in serum 1,25-(OH)2D3 and serum immunoreactive PTH show midcyclic increases or no changes. In the present study we evaluated osteoblastic activity by measuring serum OC and B-AP during the menstrual cycle in eight healthy women, aged 20-47 yr. The cycles were synchronized by LH peaks, and follicular and luteal periods were normalized by lengths. Repeated measures analysis of variance showed that serum OC varied significantly (P less than 0.05), with highest levels during the luteal period. Although the same pattern was seen for serum B-AP, the variation just failed to reach significance (P less than 0.10), but the mean level was significantly higher during the luteal than during the follicular period (P less than 0.05). Gonadotropins and ovarian sex hormones showed significant variations. There were no significant changes in serum vitamin D-binding protein, serum total and free 1,25-(OH)2D3 index, or serum immunoreactive PTH-(1-84), but serum levels of somatomedin-C showed a significant variation, with the highest level during the luteal period (P less than 0.05). Blood levels and urinary excretion of minerals exhibited no significant variations. Cross-correlation studies between OC and estradiol showed the highest correlation coefficient, when OC was lagged about 7 days after estradiol (r = 0.69; P less than 0.05). Moreover, a high correlation was found between OC and somatomedin-C when matched at concurrent time points (r = 0.76; P less than 0.01). No significant correlations were found between the other calcium-regulating hormones and OC when matched at concurrent time points. In conclusion, we found a significant effect of the menstrual cycle on the serum levels of two osteoblastic bone markers, OC and B-AP. The changes indicated that osteoblastic activity is higher during the luteal period. However, whether the changes are caused by direct or indirect effects of the fluctuations in calciotropic hormones is still unresolved.
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PMID:Changes in biochemical markers of osteoblastic activity during the menstrual cycle. 211 May 77

Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the proliferation period of osteoblast phenotype development. We present evidence that AP-1 (HeLa cell-activating protein 1) sites residing within two promoter elements of the osteocalcin gene bind the Fos-Jun protein complex: the osteocalcin box (OC box; nucleotides -99 to -76), which contains a CCAAT motif as a central element and influences tissue-specific basal levels of osteocalcin gene transcription, and the vitamin D-responsive element (VDRE; nucleotides -462 to -440), which mediates enhancement of osteocalcin gene transcription. Gel electrophoretic mobility-shift analysis demonstrated high AP-1 binding activity in proliferating osteoblasts and dramatic changes in this activity after the down-regulation of proliferation and the initiation of extracellular-matrix mineralization in primary cultures of normal diploid osteoblasts. Methylation interference analysis established at single nucleotide resolution that purified recombinant Fos and Jun proteins bind in a sequence-specific manner to the AP-1 sites within the VDRE and OC box. Similarly, an AP-1 motif within a putative VDRE of the alkaline phosphatase gene, which is also expressed after the completion of proliferation, binds the Fos-Jun complex. These results support a model in which coordinate occupancy of the AP-1 sites in the VDRE and OC box in proliferating osteoblasts may suppress both basal level and vitamin D-enhanced osteocalcin gene transcription as well as transcription of other genes associated with osteoblast differentiation--a phenomenon we describe as phenotype suppression. This model is further supported by binding of the Fos-Jun complex at an AP-1 site in the type alpha I collagen promoter that is contiguous with, but not overlapping, the VDRE. Such a sequence organization in the collagen VDRE motif is compatible with vitamin D modulation of collagen but not with osteocalcin and alkaline phosphatase expression in proliferating osteoblasts.
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PMID:Coordinate occupancy of AP-1 sites in the vitamin D-responsive and CCAAT box elements by Fos-Jun in the osteocalcin gene: model for phenotype suppression of transcription. 212 10

Recent studies have shown that treatment with the LHRH agonist nafarelin gives symptomatic and objective relief to women with endometriosis. Such a treatment, however, results in increased bone turnover and loss of bone mass. In the present study 17 women with endometriosis were treated with 400 mg nafarelin combined with 1.2 mg norethisterone (NET) for 6 months, followed by 6 months with only 1.2 mg NET. The data were compared to data from a previously published study of 9 women treated for 6 months with 400 mg nafarelin alone, followed by 6 months without treatment. In the group treated with nafarelin plus NET the biochemical parameter of bone resorption (fasting urinary hydroxyproline) remained virtually unchanged, compared to a highly significant increase in the nafarelin-treated group. Estimates of bone formation (serum alkaline phosphatase and plasma bone Gla protein) increased in the nafarelin plus NET group, but to only a minor extent compared to those in the nafarelin group. In addition, bone mineral in the forearm, the spine, and the total skeleton remained virtually unchanged in the group treated with nafarelin plus NET, compared to the bone loss of 2-6%/6 months in the nafarelin group. We conclude that addition of NET to nafarelin treatment of endometriosis seems to have a bone-sparing effect.
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PMID:Is it possible to prevent bone loss in young women treated with luteinizing hormone-releasing hormone agonists? 213 31

Because of the bone remodelling it induces, hyperthyroidism modifies the parameters of calcium-phosphorus metabolism. For a better determination of the mechanism involved, we studied 13 patients with Graves' disease compared with 13 controls. We measured the various parameters of calcium-phosphorus metabolism, notably the levels of parathormone, 25-hydroxycholecalciferol, 1-25 dihydroxycholecalciferol and ostocalcin; 8 patients were re-examined in euthyroidism. Total and corrected values of calcaemia (P less than 0.05 and P less than 0.01), phosphoreamie (P less than 0.01), alkaline phosphatase (P less than 0.01), calciuria (P less than 0.01) and hydroxyprolinuria (P less than 0.01) were significantly higher in patients with hyperthyroidism. Osteocalcin also was significantly increased (P less than 0.01) and correlated with thyroid hormone levels, thus confirming its usefulness as marker of bone remodelling in hyperthyroidism. Creatininaemia was significantly lowered (P less than 0.01). The intestinal absorption of calcium after injection of 1 g of calcium was reduced. Parathormone and 25-hydroxycholecalciferol levels were not significantly different in patients and in controls. In patients who were re-examined in euthyroidism, there was a significant increase in parathormone and in 1-25 dihydroxycholecalciferol levels (P less than 0.05). Thus, in situations of hyperthyroidism 2 elements contribute to a deficit in calcium balance: (a) a fall in parathormone level, consecutive to a rise in calcaemia, induces hypercalciuria; and (b) a fall in 1-25 dihydroxycholecalciferol level, consecutive to functional hypoparathyroidism and hyperphosphoraemia, results in a decrease of intestinal calcium absorption.
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PMID:[Phosphorus-calcium metabolism in hyperthyroidism]. 213 61

Hormone-dependent accumulation of specific binding sites for 1,25(OH)2D3 and changes in human 1,25-dihydroxy-vitamin D receptor (hVDR) mRNA levels were examined in cell lines (MG-63, SaOs-2 and U2-Os) derived from human bone. Osteocalcin synthesis and secretion as well as alkaline phosphatase activity were also characterized as biochemical markers of the osteoblastic phenotype. Specific binding sites for 1,25(OH)2D3 were quantified by incubating cultured intact cells with [3H]1,25(OH)2D3 at 37 degrees C. Based on the uptake of 1,25(OH)2D3, there were about 3000 to 4000 receptor molecules per cell with apparent dissociation constants varying between 0.02 to 0.03 nM. The binding was saturated with 1,25(OH)2D3 in 3 to 6 h after the hormone addition and further exposure to the hormone resulted in an upregulation of the bindings sites. The levels were elevated by as little as 10 to 200 pM 1,25(OH)2D3, and maximal binding was achieved with 0.2-0.7 nM 1,25(OH)2D3. Treatment with 1,25(OH)2D3 also resulted in a clear increase (about 3-fold) in hVDR mRNA by 24 h in all three cell lines. The increase in hVDR mRNA level was time- and dose-dependent. MG-63 cells responded with 2- and 15-fold increases, respectively, in intracellular and secreted levels of osteocalcin after the 1,25(OH)2D3-treatment. In dot-blot hybridization assay, MG-63 cells expressed osteocalcin mRNA which was inducible with 1,25(OH)2D3 while, in SaOs-2 and U2-Os cells, osteocalcin mRNA was not detected under the same circumstances. Also, no secretion of osteocalcin was detected in SaOs-2 and U2-Os cells with or without addition of 1,25(OH)2D3.
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PMID:Effect of 1,25(OH)2D3 on its receptor mRNA levels and osteocalcin synthesis in human osteosarcoma cells. 215 13

A human osteosarcoma cell line, HuO9, was established from a tumor that was heterotransplanted into athymic nude mice. Antiserum against nude mouse spleen cells was added to the early passage cultures to eliminate the host fibroblastic cells. The cell line retained a high activity of liver/bone/kidney-type alkaline phosphatase (ALP) and secreted osteocalcin, i.e., bone gamma-carboxyglutamic acid-containing protein (BGP), into the medium. The addition of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increased the ALP activity as well as the level of BGP secreted into the medium. The ALP of 1,25(OH)2D3-treated cells has the same inhibition characteristics to heat and amino acids as that of untreated cells. Synthetic human parathyroid hormone stimulated the production of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) approximately 100-fold within five minutes. However, the stimulation was not observed with a synthetic human thyrocalcitonin. When HuO9 cells were transplanted into the back of a nude mouse, a tumor with an abundant osteoid formation and mineralization was produced. The results indicate that the HuO9 cell line expresses well-differentiated osteoblastic phenotypes. HuO9 is the first established human cell line to produce BGP, and it provides a useful model for the studies of osteoblasts and the regulatory mechanisms of BGP production.
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PMID:A newly established human osteosarcoma cell line with osteoblastic properties. 217 70


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