Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of caffeine exposure on bone formation were examined using a chick osteoblast culture system. Secondary cultures of normal diploid osteoblasts were exposed to chronic doses of 0, 0.1, 0.2, or 0.4 mM caffeine beginning on day 0 through day 28. Neither the rate of cell proliferation nor cell number, as measured by total DNA, was decreased for any of the doses examined. In contrast, osteocalcin levels, alkaline phosphatase activity, and total calcium levels showed a dose-related decrease in cultures treated with caffeine. These parameters were significantly decreased at the highest dose of 0.4 mM. The reduction in total protein levels ranged from 29 to 66% of control values and was independent of dose. In contrast, total collagen levels were more affected by the dose of caffeine used. Inhibition of collagen levels was most apparent on days 17 and 21, time points during the period of active formation of the matrix immediately preceding the deposition of mineral. By day 28 collagen levels in cultures exposed to the lower doses of caffeine had returned to control levels, and only the cultures exposed to the highest dose (0.4 mM) remained significantly inhibited with respect to both collagen and mineral. Histochemically, alkaline phosphatase and mineral staining of day 28 cultures mirrored the biochemical events with the 0.4 mM caffeine exposure. The results indicate that one of the effects of caffeine on bone development is to inhibit the formation of a competent extracellular matrix during the osteoblast differentiation sequence, which results in the inhibition of mineralization analogous to the delayed ossification observed in fetal animals after prenatal caffeine exposure.
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PMID:Effect of caffeine on parameters of osteoblast growth and differentiation of a mineralized extracellular matrix in vitro. 179 50

Osteoblasts, the bone-forming cells, synthesize the macromolecules of the bone matrix including: type I collagen; osteocalcin; osteonectin; osteopontin; proteoglycan I and II; bone sialoprotein; matrix gla-protein; bone glycoprotein 75; several other proteins, which have not been extensively characterized; growth factors, including transforming growth factor beta and fibroblast growth factor. Osteoblasts also have high levels of the membrane-bound enzyme, alkaline phosphatase, which plays a role in matrix mineralization, and receptors for tissue-specific hormones, such as parathyroid hormone, as well as many other hormones, cytokines and growth factors, which regulate bone growth, differentiation and metabolism. The expression of these various proteins, most of which are not unique to bone but which together characterize the bone phenotype, is induced during osteoblastic differentiation in a stepwise fashion, suggestive of multiple regulatory factors. The detailed sequence of the expression of osteoblastic genes in situ has not been fully characterized. It appears that type I collagen and alkaline phosphatase are expressed early during the commitment to the osteoblastic phenotype, whereas osteopontin and osteocalcin appear late during osteoblastic differentiation. Diversity among "osteoblastic" cells is also apparent, probably not all osteoblastic cells express all the features. A large number of osteoblastic models are currently available to study the expression of osteoblast-related genes in vitro. These include primary cultures from calvaria or trabecular bone from several species, including humans, osteosarcoma-derived cell lines, and experimentally immortalized cells. Some of these in vitro models, especially the calvaria-derived cultures, undergo changes which mimic osteoblastic differentiation in vivo. The study of these and other cell models started providing insights into the regulation of gene expression in osteoblastic cells. In addition to a vast body of information on the conditions required for the expression of various proteins in culture and their regulation by hormones and growth factors, more detailed information on specific genes has recently been obtained. For example, regulation of type I collagen gene expression has been studied in osteosarcoma cell lines where 1,25(OH)2 vitamin D3 was shown to act via specific DNA segment(s) in the 5' flanking region of the gene, while parathyroid hormone affected gene expression by altering the stability of the transcripts. TGF beta 1, which stimulates osteogenesis, was shown to promote the transcription of osteopontin and type I collagen, the latter effect requiring the binding site for the transactivating protein, nuclear factor I.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gene expression in osteoblastic cells. 180 5

The analogue of calcitriol, calcipotriol (MC 903, Daivonex) has been proven effective in the treatment of psoriasis, when given topically. However, the possible influence of cutaneously absorbed MC 903 on calcium metabolism is still unclear. We evaluated various parameters of calcium metabolism in 17 psoriatic patients treated for 5.4 +/- 2.3 (mean +/- SD) weeks with MC 903, on 16 +/- 6% of the body surface. The dose administered (100 g of Daivonex corresponding to 5 mg of MC 903) decreased the PASI score by 40.9 +/- 20.0% (p less than 0.001). Among these patients, 12 were studied before and after MC 903 therapy. In none could be detected any change in protein-adjusted calcium, ionized Ca, plasma levels of creatinine, alkaline phosphatase, osteocalcin, intact parathyroid hormone (PTH), calcidiol and calcitriol, or in daily or fasting urinary excretion of Ca or cAMP. After an MC-903-free period, 9 patients received 1.5 micrograms/day of calcitriol orally for 7 days. Whereas this treatment did not control the skin relapse in most of the patients, it induced a significant increase in plasma levels of protein-adjusted Ca and calcitriol, and in 24-hour urinary Ca excretion, as well as a significant fall in PTH as compared with pretreatment values. These results indicate that 150 micrograms/day of MC 903, despite a possible 1% absorption, i.e. a systemic dose of 1.5 micrograms, did not produce any detectable alteration of Ca metabolism, whereas an equivalent dose of oral calcitriol was associated with significant changes. The threshold dose of topical calcipotriol that might induce alterations similar to 1.5 micrograms/day of oral calcitriol remains to be evaluated.
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PMID:Effects of topical calcipotriol on calcium metabolism in psoriatic patients: comparison with oral calcitriol. 180 90

The effect of the calcium antagonist verapamil on calcium homoeostasis and bone metabolism has been investigated in a double-blind randomized placebo-controlled study. Ten patients randomized to verapamil 120 mg t.i.d. and 9 patients randomized to placebo in The Danish Verapamil Infarction Trial II took part in the study. Bone formation, estimated by 24-h whole body retention of diphosphonate (WBR), osteocalcin, alkaline phosphatase and calcium metabolic indices, was recorded before the start of medication and after 1 and 6 months of treatment. Baseline calcium metabolic variables were not significantly different between the two study groups. There were no significant differences in WBR (0.38 vs 0.37), osteocalcin level (8.2 vs 8.0 micrograms/l) or alkaline phosphatase (218 vs 200 U/l) after treatment for 6 months with verapamil compared to placebo. Serum PTH, calcium and phosphate levels were also not affected by verapamil. The results suggest that prolonged treatment with clinical doses of verapamil does not affect indices of calcium and bone metabolism in humans.
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PMID:Changes in calcium homoeostasis and bone formation in patients recovering from acute myocardial infarction: effect of verapamil treatment. Danish Study Group on Verapamil in Myocardial Infarction. 181 63

When mechanical stress is applied, osteoblasts have shown to produce bone turnover stimulating hormones and enzymes like prostaglandin E2 (PGE2), cyclic AMP, alkaline phosphatase, and collagenase. Osteocalcin (bone Gla protein) is also a protein produced by osteoblasts to control bone metabolism. Thus, its production may also be stimulated by mechanical stress. The purpose of this investigation was to test if mechanical stress stimulates osteoblast-like cells to produce osteocalcin in vitro. The results suggest that osteocalcin production is stimulated at the initial stage of the culture by cyclic tension and relaxation force, and secretion may decrease with time.
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PMID:Mechanical stress as a stimulant to the production of osteocalcin in osteoblast-like cells. 181 33

We have previously shown that osteocalcin synthesis is readily induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in MG-63 human osteosarcoma cells (Mahonen et al. (1990) Biochim. Biophys. Acta 1048, 30-37). In the present study, the regulation of osteocalcin synthesis by other hormones of the steroid-thyroid hormone family (retinoic acid, 17 beta-estradiol, triiodothyronine, and dexamethasone) was examined. We found that the other hormones alone had no effects on medium osteocalcin and osteocalcin mRNA concentrations by 96 h of treatment. Compared with 1,25(OH)2D3, however, the combination of 1,25(OH)2D3 with dexamethasone resulted in a greatly reduced medium osteocalcin concentration. Also estradiol and triiodothyronine diminished the stimulatory effect of 1,25(OH)2D3. In contrast, the combination of 1,25(OH)2D3 with retinoic acid resulted in an increased medium osteocalcin concentration. The inhibition of osteocalcin synthesis by dexamethasone and triiodothyronine was accompanied by decreased osteocalcin mRNA levels. Retinoic acid and estradiol, however, did not influence the 1,25(OH)2D3-induced osteocalcin mRNA levels. To examine the specificity of the hormonal effects, the activity of alkaline phosphatase was determined. Both baseline and 1,25(OH)2D3-stimulated alkaline phosphatase activity was found to be inhibited by all other hormones. These results suggest that the steroidal hormones specifically affect osteocalcin synthesis in osteoblastic bone cells, and that complex interactions occur at the level of transcription and/or translation resulting in each case in a finely adjusted rate of osteocalcin synthesis.
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PMID:Modulation of 1,25(OH)2D3-induced osteocalcin synthesis in human osteosarcoma cells by other steroidal hormones. 182 Sep 70

The non-invasive assessment of bone turnover has received increasing attention over the past few years because of the need for sensitive markers in the clinical investigation of osteoporosis. Markers of bone formation include serum total and bone-specific alkaline phosphatase, serum osteocalcin, and measurement of serum type I collagen extension peptides. Assessment of bone resorption can be achieved with measurement of urinary hydroxyproline, urinary excretion of the pyridinium crosslinks (Pyr and D-Pyr), and by measurement of plasma TRAP activity. For the screening of bone turnover in women at the menopause, and for the assessment of the level of bone turnover in elderly women with vertebral osteoporosis, serum osteocalcin and urinary Pyr and D-Pyr appear to be the most sensitive markers so far. Programmes combining bone mass measurement and assessment of bone turnover in women at the time of the menopause have been developed in an attempt to improve the assessment of the risk for osteoporosis. Efforts are being made to develop more convenient assays and to identify other markers of bone turnover. In the future a battery of various specific markers is likely to improve the assessment of the complex aspects of bone metabolism, especially in osteoporosis.
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PMID:What do we know about biochemical bone markers? 182 19

We have used the cynomolgus macaque as a model for the study of the effects of endogenous and exogenous sex steroid hormones on atherosclerosis and osteoporosis. As in human beings, premenopausal female cynomolgus macaques develop much less extensive coronary artery atherosclerosis than their male counterparts. Furthermore, surgical menopause results in a more atherogenic plasma lipoprotein pattern and an approximate doubling of atherosclerosis extent. Frequent pregnancy, a hyperoestrogenic state, results in an approximate 50% reduction in atherosclerosis extent. Physiological replacement with 17 beta-oestradiol alone or in combination with progesterone prevents the increase in coronary artery atherosclerosis extent associated with ovariectomy. This effect is independent of plasma lipoprotein concentrations and appears to be accounted for, at least in part, by an inhibitory effect of oestrogen replacement therapy on the uptake and degradation of LDL by the artery wall. Also, as in human beings, treatment with certain types of combination oral contraceptives results in marked decreases in plasma HDL-C concentration. Nonetheless, coronary artery atherosclerosis extent is reduced in monkeys by oral contraceptive treatment, and this effect is most pronounced among animals at highest risk due to theoretically adverse plasma lipoprotein profiles. It appears that, as with oestrogen replacement therapy, this effect can be accounted for, at least in part, by an inhibition of the uptake and degradation of low density lipoprotein by the artery wall. The monkey also appears to be a good model for studies of postmenopausal bone loss. As in women, surgical menopause results in significant diminution of bone mineral density and bone mineral content. Also, serum biomarkers of bone turnover (total alkaline phosphatase, acid phosphatase, tartrate-resistant acid phosphatase and osteocalcin) are increased in surgically postmenopausal monkeys, indicating increased bone turnover resulting from the surgical menopause. These increases in bone loss and indices of bone turnover were prevented by physiological oestrogen replacement therapy. Cynomolgus monkeys seem to be exceptionally useful models for studies of the effects of sex steroid hormones on atherosclerosis and osteoporosis, two major public health problems in postmenopausal women.
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PMID:Effects of oestrogens and progestogens on coronary atherosclerosis and osteoporosis of monkeys. 182 26

28 consecutive patients with multiple osteolytic bone metastases due to various types of cancer were treated with 300 mg/day of sodium clodronate given intravenously as a 3-hour infusion, 16 patients were treated for 10 days and 12 for 20 days. Our findings showed that clodronate administration causes an increase in serum osteocalcin (sBGP) in the group of patients treated for 20 days (p less than 0.05), a reduction in serum Ca in both groups of patients (p less than 0.01), an increase in serum alkaline phosphatase (p less than 0.05 and p less than 0.01), a reduction in urinary Ca (p less than 0.01) and a reduction in uOHP (p less than 0.05). The raise in sBGP may be attributed to the reduction of sCa and to the consequent secondary hyperparathyroidism. The increase in sBGP can be considered as the expression of osteoblasts stimulation following an adequate period of therapy with sodium clodronate.
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PMID:Clodronate treatment increases serum osteocalcin in normocalcemic osteolytic bone metastases. 182 99

Long-acting medroxyprogesterone acetate (MPA) effect on some important parameters of calcium metabolism in patients with glucocorticoid-induced osteoporosis (GCO) was evaluated. Twelve steroid-dependent asthmatic male patients with GCO were administered 200 mg of MPA (Depo-Provera) intramuscularly, and had fasting serum samples obtained at baseline and at weekly intervals for 5 consecutive weeks. Baseline serum samples were also obtained from 12 control healthy male subjects matched for age. The following measurements were made from each serum sample: osteocalcin (OC), skeletal (SAP) and total alkaline phosphatase (TAP), calcitonin (C), insulin-like growth factor I (IGF1), 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D. Significantly lower baseline serum levels of OC and C were found in the patients with GCO than in controls (P less than 0.001). Following MPA administration in GCO patients statistically significant and sustained increases in OC, SAP and C were noticed during the next 5 weeks. No significant differences in baseline levels for TAP, IGF1, 1,25(OH)2D and 25(OH)D between GCO patients and controls were found, and no significant changes following MPA administration in GCO patients were obtained for these parameters. In conclusion, when administered to patients with GCO, MPA seems to stimulate the osteoblastic activity as suggested by sustained increases in OC and SAP serum levels, and also enhances the C production by the C-cells of the thyroid.
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PMID:Effects of medroxyprogesterone acetate on some parameters of calcium metabolism in patients with glucocorticoid-induced osteoporosis. 182 84


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