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)

Glucocorticoid-induced osteoporosis is believed to be caused by increased bone resorption and decreased bone formation. However, the direct effects of glucocorticoids on bone formation are, as yet, not fully understood. Cortisol, corticosterone, and dexamethasone were examined for their effects on alkaline phosphatase activity, the incorporation of [3H]proline into type I collagen, DNA content, and mitotic index in intact 21-day-old fetal rat calvariae. After 24 h of treatment, cortisol at 1-100 nM increased the incorporation of [3H]proline into type I collagen, whereas at 1-10 microM, cortisol inhibited type I collagen labeling. After 96 h, cortisol (0.1-10 microM) had an inhibitory effect on type I collagen labeling and alkaline phosphatase activity. Cortisol had a small, not dose dependent, and transient stimulatory effect on alkaline phosphatase which appeared after 12-24 h of exposure, whereas the inhibitory effect was dose related, it appeared and was near-maximal after 48 h of continuous treatment with cortisol. Corticosterone and dexamethasone had an effect similar to that of cortisol on type I collagen synthesis and alkaline phosphatase activity. None of the steroids tested affected the release of the enzyme into the culture medium. Cortisol, corticosterone, and dexamethasone did not alter calvarial DNA content after 24 h of treatment, but after 96, concentrations of 1 nM to 10 microM were inhibitory. The decrease in DNA appeared after 48 h of exposure to 100 nM cortisol and was maximal after 72 h. Histological sections showed a marked and generalized decrease in the number of mitoses after colcemid arrest in calvariae treated with 100 nM cortisol, corticosterone, or dexamethasone for 96 h. These studies indicate that glucocorticoids have a dual effect on type I collagen synthesis and alkaline phosphatase activity in cultured calvariae: a transient stimulatory effect after short term treatment and an inhibitory one after long term exposure. The latter is related to a generalized decrease in cell population.
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PMID:Effect of glucocorticoids on type I collagen synthesis, alkaline phosphatase activity, and deoxyribonucleic acid content in cultured rat calvariae. 682 19

A method is presented for isolating osteoblasts from newborn mouse calvaria without the use of digestive enzymes. The procedure is based on the ability of osteoblasts to migrate from bone onto small glass fragments (Jones, S.J., and A. Boyde, 1977, Cell Tissue Res., 184:179-193). The isolated cells were cultured for up to 14 d in Dulbecco's modified Eagle's medium supplemented with 10% fetal calf serum and 50 micrograms/ml of ascorbic acid. 7-d cultures were incubated for 24 h with [3H]proline. High levels of collagen synthesis relative to total protein were found, as measured by collagenase digestion of medium and cell layer proteins. Analysis of pepsin-digested proteins from the same cultures by SDS PAGE showed that type I collagen was predominantly produced with small amounts of type III and V (alpha 1 chains) collagens. Osteoblasts grown in the presence of beta-glycerophosphate were able to initiate mineral deposition in culture. Electron microscopic analysis of the cultures revealed the presence of needle-shaped apatite-like crystals associated with collagen fibrils and vesicles in the extracellular space. Mouse skin fibroblasts cultured under identical conditions failed to initiate mineralization. Electron histochemical studies revealed the presence of alkaline phosphatase activity, associated with osteoblast membranes, matrix vesicles and on or near collagen fibrils. Thus these isolated osteoblasts retained in culture their unique property of initiating mineralization and therefore represent a model of value for studying the mineralization process in vitro.
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PMID:Osteoblasts isolated from mouse calvaria initiate matrix mineralization in culture. 683 75

Water soluble derivatized dextran named E9 with a molecular weight of 45,000 g l-1 containing 58% methyl carboxylic acid unit, 19% benzylamide unit, and 26% sulfonate with a specific anticoagulant activity of 0.29 IU mg-1 was studied for its effects on human osteoblast growth and phenotype expression for short-term treatment. At concentrations between 1 ng ml-1 and 1 microgram ml-1 E9 has no effect on DNA synthesis whereas at higher concentrations DNA synthesis is inhibited in a dose related fashion (87% for 400 micrograms ml-1). For concentrations which do not modify osteoblast growth, E9 promotes alkaline phosphatase activity, type I collagen and osteocalcin synthesis with a maximum effect for 0.1-1 microgram ml-1. It has a synergistic effect with hPTH increasing AMPc. Moreover, osteonectin synthesis was enhanced in a dose-dependent manner between 0.1 and 5 micrograms ml-1. These results seem to indicate that E9 is able to stimulate human osteoblast phenotype expression and could be useful in clinical applications.
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PMID:Effect of a derivatized dextran on human osteoblast growth and phenotype expression. 752 43

Markers of bone formation determined in serum include alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin [bone gamma-carboxyglutamic acid peptide (BGP) and procollagen type I carboxyterminal propeptide. Recently, advances have been made in the immunoassay of bone-specific alkaline phosphatase. This is a marker for osteoblastic activity; it is very stable and is not primarily dependent on kidney function because it is degraded in the liver. BGP is not specific for bone formation because it increases in serum during bed rest (which involves increased bone resorption), and it is not stable. Furthermore, the elimination of BGP is dependent on glomerular filtration rate. Procollagen type I carboxyterminal propeptide is not as sensitive as bone-specific alkaline phosphatase because it increases less in women after the menopause. Urinary pyridinoline and deoxypyridinoline determined by high-performance liquid chromatography are regarded as the best methods for measuring bone resorption. These might be replaced by type I collagen crosslinked N-telopeptide or CrossLaps in the future in laboratories not equipped with a high-performance liquid chromatography system. Serum markers of bone resorption are currently under investigation. An immunoassay for the tartrate-resistant acid phosphatase in serum should be a very promising tool for the quantification of bone resorption.
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PMID:Noninvasive parameters of bone metabolism. 755 99

Biochemical markers of bone metabolism were analysed in serum samples obtained from 60 horses with no history of orthopaedic disease (age 3 months-20 years). Serum levels of the carboxyterminal propeptide of type I procollagen (PICP), a marker of bone formation and the pyridinoline cross linked telopeptide domain of type I collagen (ICTP), a putative marker of bone resorption, were measured by radioimmunoassay (RIA). Serum levels of the bone specific isoenzyme of alkaline phosphatase (BALP), another marker of bone formation, were measured by a wheatgerm agglutinin affinity (WGA) method. Total alkaline phosphatase levels were also determined. Serum levels of PICP were significantly correlated with bone ALP (r = 0.78, P < 0.0001) and ICTP (r = 0.87, P < 0.0001). ICTP levels also correlated significantly with bone ALP (r = 0.81, P < 0.0001). However, total alkaline phosphatase did not correlate significantly with PICP, ICTP and BALP in horses over 1 year of age. There was an inverse correlation between serum levels of all biochemical markers and age of animals, with the most significant changes seen over the first 2 years. In animals less than 1 year of age, the reference ranges (mean +/- s.d. 1.96) were as follows: PICP 1216-2666 micrograms/l, ICTP 13.8-26.7 micrograms/l, bone ALP 134-288 u/l and total ALP 223-498 u/l. In 2-year-olds, the equivalent reference ranges were: PICP 550-1472 micrograms/l, ICTP 7.96-22.8 micrograms/l, bone ALP 32.7-125 u/l and total ALP 134-238 u/l.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age related changes in biochemical markers of bone metabolism in horses. 755 47

We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 pre- and 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased considerably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 premenopausal patients with active CS and a control group of 18 age-matched healthy premenopausal women. However, the urinary hydroxyproline/creatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 vs. 16.2 +/- 3.5 mumol/mmol, P < 0.01). In all 9 premenopausal patients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SEM, P < 0.0001), indicating a prompt increase of osteoblast activity. Also serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked telopeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased significantly between 0 and 3 months. Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome. 755 64

Serum levels of procollagen type I carboxy-terminal extension peptide (PICP) reflect the synthesis of type I collagen. As PICP is produced by osteoblasts and is not incorporated into bone matrix, serum PICP levels have been suggested as a marker of bone formation. In 37 cancer patients (21 men and 16 women; age: 72.4 +/- 8.6 (mean +/- SD) years) with bone metastases and 23 women (age: 77.3 +/- 6.64 years) as controls, the following biochemical variables were measured: serum PICP, calcium (Ca), phosphorus, alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline and calcium corrected for creatinine excretion. Higher serum levels of PICP were observed in cancer patients than in control (245 +/- 177 micrograms/l vs 121.7 +/- 36 micrograms/l, p < 0.01). Cancer patients also had higher AP levels than controls (704 +/- 755 U/l vs 216.5 +/- 56 U/l, p < 0.01). Abnormal PICP and AP serum concentrations (above the mean + 2SD of controls) were found in 46% and 51% of patients, respectively. Moreover, patients showed significantly lower serum calcium concentrations (p < 0.001), and higher TRAP and hydroxyproline levels although statistical significance was not reached. In the patients, PICP was correlated directly with AP (r = 0.50, p < 0.01) and TRAP (r = 0.34, p < 0.05). In conclusion, patients with bone metastases have increased bone turnover as shown by serum markers. Serum PICP may be used as an adjunctive, non-invasive index to assess bone metabolism. However, the clinical usefulness of PICP in cancer patients needs further evaluations.
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PMID:Serum levels of procollagen type I carboxyterminal extension peptide in cancer patients with bone metastases. 756 Dec 34

In order to investigate collagen metabolism in two different types of autosomal dominant osteopetrosis (ADO), eight patients with type I (aged 23-61 years, mean 40.4 years) and nine patients with type II ADO (aged 20-49 years, mean 32.8 years) were compared with ten normal controls (aged 22-54 years, mean 35.4 years). The subjects were treated with 100 micrograms of triiodothyronine (T3) daily for 7 days and followed for a total of 4 weeks. Serum T3 increased in all subjects and a corresponding suppression of thyroid-stimulating hormone (TSH) was observed. Serum carboxy-terminal propeptide of type I collagen (S-PICP) in the control and type I groups showed no difference at baseline, whereas type II was lower than controls (p < 0.01). No significant alterations following stimulation were observed in any of the groups. Serum BGP (osteocalcin) values in the two patient groups were insignificantly lower than controls both at baseline and throughout the study. Following stimulation, a significant response was seen in the three groups (p < 0.001). The increases during the treatment period (delta values) for controls, type I and type II were 47.6% (p < 0.01), 51.7% (p = 0.05) and 34.8% (NS), respectively, with no difference between the groups. Serum bone-specific alkaline phosphatase (S-ALP) was not different between the groups and no alterations were observed in relation to treatment. The serum N-terminal propeptide of type III collagen (S-PIIINP) showed no difference at baseline between type I and controls but was significantly higher (p < 0.003) in type II than in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Collagen metabolism in two types of autosomal dominant osteopetrosis during stimulation with thyroid hormones. 758 85

Blood biochemical indices of bone turnover were followed up for 1 month in six dogs with experimental osteomyelitis. The bone infection resulted in significant increase in parameters of bone formation (serum bone alkaline phosphatase and serum osteocalcin) and bone resorption [serum carboxyterminal telopeptide of type I collagen (i-ICTP)] as early as the end of the second week after the operation and inoculation. There was strong evidence that serum i-ICTP levels could be useful for the early diagnosis of postoperative complications in veterinary orthopedics, such as posttraumatic osteomyelitis.
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PMID:Changes in serum carboxyterminal telopeptide of type I collagen in an experimental model of canine osteomyelitis. 758 76

We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.
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PMID:Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease. 758 48


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