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 Runx2/Cbfa1 transcription factor is a scaffolding protein that promotes osteoblast differentiation; however, the specific Runx2-functional domains required for induction of the osteogenic lineage remain to be identified. We approached this question using a TERT-immortalized cell line derived from calvaria of Runx2-null mice by reconstituting the osteogenic activity with wild-type and deletion mutants of Runx2. The presence or absence of osteogenic media (beta-glycerol phosphate and ascorbic acid) and/or with BMP2 did not stimulate osteoblastic gene expression in the Runx2-null cells. However, cells infected with wild-type Runx2 adenovirus showed a robust temporal increase in the expression of osteoblast marker genes and were competent to respond to BMP2. Early markers (i.e., collagen type-1, alkaline phosphatase) were induced (four- to eightfold) at Days 4 and 8 of culture. Genes representing mature osteoblasts (e.g., Runx2, osteopontin, bone sialoprotein, osteocalcin) were temporally expressed and induced from 18- to 36-fold at Days 8 and 12. Interestingly, TGFbeta and Vitamin D-mediated transcription of osteoblast genes (except for osteopontin) required the presence of Runx2. Runx2 lacking the C-terminal 96 amino acids (Runx2 Delta432) showed a pattern of gene expression similar to wild-type protein, demonstrating the Groucho interaction and part of the activation domain are dispensable for Runx2 osteogenic activity. Upon further deletion of the Runx2 C-terminus containing the nuclear matrix targeting signal and Smad-interacting domain (Delta391), we find none of the osteoblast markers are expressed. Therefore, the Runx2 391-432 domain is essential for execution of the BMP2 osteogenic signal.
 ...
PMID:Reconstitution of Runx2/Cbfa1-null cells identifies a requirement for BMP2 signaling through a Runx2 functional domain during osteoblast differentiation. 1692 9

Secondary hyperparathyroidism (SHPT) is a common, important, and treatable complication of end-stage renal disease. This study was conducted to investigate the role of serum magnesium (Mg) in regulating the secretion of parathyroid hormone (PTH) by the parathyroid gland in patients on maintenance hemodialysis (HD). Pre-dialysis serum levels of calcium (Ca), phosphorus (P), Mg, alkaline phosphatase (ALP), intact serum PTH (iPTH), serum 25-hydroxy Vitamin D (25-OH Vit D) and plasma bicarbonate (HCO3) were measured. The Urea Reduction Rate as well as duration and dosage of HD treatment were noted. Our study did not show any significant correlation between serum Mg levels and duration of HD treatment, levels of serum ALP, and plasma HCO3, Ca and P. An inverse correlation, albeit insignificant, was found between the serum Mg levels and iPTH (r = -0.30 p = 0.079); also, a significant positive correlation was found between serum Mg levels and serum 25-OH Vit D levels (r = 0.40 p = 0.009). Our findings are in agreement with previous data, which suggest that factors other than serum Mg are more important in the regulation of PTH secretion in HD patients. A positive and strong association between serum Mg with 25-OH Vit D needs to be studied in greater detail.
 ...
PMID:Correlation of serum magnesium with serum parathormone levels in patients on regular hemodialysis. 1697 Feb 54

Vitamin D is an important regulator of mineral homeostasis and bone metabolism. 1Alpha-hydroxylation of 25-(OH)D3 to form the bioactive vitamin D hormone, 1alpha,25-(OH)2D3, is classically considered to take place in the kidney. However, 1alpha-hydroxylase has been reported at extrarenal sites. Whether bone is a 1alpha,25-(OH)2D3 synthesizing tissue is not univocal. The aim of this study was to investigate an autocrine/paracrine function for 1alpha,25-(OH)2D3 in bone. We show that 1alpha-hydroxylase is expressed in human osteoblasts, as well as the vitamin D binding protein receptors megalin and cubilin. Functional analyses demonstrate that after incubation with the 1alpha-hydroxylase substrate 25-(OH)D3, the osteoblasts can produce sufficient 1alpha,25-(OH)2D3 to modulate osteoblast activity, resulting in induced alkaline phosphatase (ALP) activity, osteocalcin (OC) and CYP24 mRNA expression, and mineralization. The classical renal regulators of 1alpha-hydroxylase, parathyroid hormone, and ambient calcium do not regulate 1alpha-hydroxylase in osteoblasts. In contrast, interleukin (IL)-1beta strongly induces 1alpha-hydroxylase. Besides the bone-forming cells, we demonstrate 1alpha-hydroxylase activity in the bone resorbing cells, the osteoclasts. This is strongly dependent on osteoclast inducer RANKL. This study showing expression, activity, and functionality of 1alpha-hydroxylase unequivocally demonstrates that vitamin D can act in an auto/paracrine manner in bone.
 ...
PMID:Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells. 1702 19

Epidemiological studies reveal fracture incidence in epilepsy is twice that of the normal population. Much interest has been focused on Vitamin D, however, considering mixed results on non-enzyme inducing anti-epileptic drugs (AEDs) and bone mineral density (BMD) additional metabolic effects may be to blame. AEDs increase serum homocysteine (s-Hcy) by lowering blood folate levels. An association between elevated homocysteine, BMD and increased fracture incidence has been found in non-epilepsy populations. Additionally, folate and Vitamin B12 levels are independently related to bone mineral density in various non-epilepsy populations. This study supports previous research, which found elevated s-Hcy in subjects taking AEDs and that bone loss is related to the use of enzyme-inducing AEDs and changes in alkaline phosphatase. By one-way ANOVA, subjects on phenytoin monotherapy had significantly higher levels of s-Hcy than those on other AEDs (F=5.89, p=.016). Regression analyses revealed homocysteine, fracture history, length of years on AEDs, ethnicity were predictors of spine T scores. Weight and BMI were predictors of both BMD and DEXA T scores. Use of enzyme-inducing AEDs was a negative predictor of spine BMD and T scores, while phenytoin monotherapy was a positive predictor of spine BMD. Lamotrigine was found to be a negative predictor of spine T score. Ambulatory status, menopause and alcohol consumption were predictors of BMD but not T scores. In this study, persons with epilepsy who take nutritional supplementation have 25% lower s-Hcy levels than those who do not. Supplementation continues to be important in preventative epilepsy care.
 ...
PMID:Homocysteine and bone loss in epilepsy. 1711 Jan 34

The fundamental role of Vitamin D has been long known in regulating calcium homeostasis and bone metabolism. An increased contribution of Vitamin D was recently described in association with a lower incidence of Rheumatoid Arthritis (RA). This must not be surprising, as the immunomodulating effects of Vitamin D are clear, which have been attributed protective effects in autoimmune disorders such as some chronic inflammatory bowel diseases, multiple sclerosis and type I diabetes. An interaction was suggested between Vitamin D metabolism and inflammation indexes through mediation of TNF-alpha which is also especially involved in osteoclastic resorption and therefore in bone loss processes. Some preliminary data would indicate an association between seasonal changes of Vitamin D serum levels, latitude and disease activity (DAS28) in RA patients. Consequently, the Osteoporosis and Metabolic Bone Diseases Study Group of SIR believes that there are grounded reasons for assessing the Vitamin D status of RA patients in order to investigate whether this is to be related to physiopathological and clinical aspects of disease other than those of bone involvement. Primary end point of the study will be to assess the levels of 25 OH Vitamin D in RA patients. Secondary endpoints will include correlation with dis-ease activity, densitometry values and bone turnover. The cross-sectional study will enroll patients of both sex genders, age ranging between 30 and 75 years according to the 1988 ACR criteria, onset of symptoms at least 2 years prior to study enrollment. Patients will be excluded suffering from osteo-metabolic diseases, liver and kidney insufficiency and those administered Vitamin D boli in the previous 12 months. Disease activity will be evaluated with the HAQ. Hemato-chemical tests and femoral and lumbar bone densitometry will be performed, unless recently undergone by patients. Blood levels of 25 OH C Vitamin D and PHT and of the two bone remodelling markers (bone alkaline phosphatase and serum CTX) will be measured, as well. Patient enrollment will start on February 2007 and will last 4 months. By the end of 2007 the study will be concluded and results will be published.
 ...
PMID:[Study of vitamin D status of rheumatoid arthritis patients. Rationale and design of a cross-sectional study by the osteoporosis and metabolic bone diseases study group of the Italian Society of Rheumatology (SIR)]. 1721 21

Substantial losses of skeletal tissue occur during late pregnancy and lactation. The goal of the present study was to follow these changes in pregnant and lactating goats and sheep, compare these two species during their second lactation, and also compare the results to the first lactation. Blood samples were collected from 12 adult dairy goats (Saanen goat) and sheep (Ostfriesen milk sheep) monthly during gestation, 2 or 3 days postpartum (pp), 2 weeks pp, 4 weeks pp, and then monthly during lactation until 7 months after parturition. Total bone mineral content (BMC) and total bone mineral density (BMD) were quantified using peripheral quantitative computed tomography (pQCT) at the same intervals as the blood was taken. Bone resorption was assessed in serum using two different domains of the carboxyterminal telopeptide of type I collagen (ICTP and crosslaps). Bone formation was quantified in serum with osteocalcin (OC) and bone-specific alkaline phosphatase (bAP). In addition, Ca and 1,25 dihydroxy vitamin D (VITD) were determined in serum. The same procedure was done during the first and second gestation and lactation. Mean ICTP and crosslaps concentrations of the two animal species showed an increase in the last month of gestation. In contrast, mean OC concentrations decreased slowly from the 2nd month of pregnancy until the first week pp. Also mean bAP activities showed a similar time course. Total BMC and BMD decreased until the first week pp in both species. Afterwards, BMC increased again during lactation. BMD levels of sheep and goats returned to prepartum levels during lactation. Vitamin D concentrations peaked in the first week pp. Only VITD concentrations in goats stayed elevated compared with prepartum values throughout the whole lactation during the second lactation. Around parturition and at the beginning of lactation, the bone resorptive phase of bone remodelling is accelerated, but is uncoupled from the process of bone formation. The mineral decrease in bone of these lactating animals seems to be reversible. Since during lactation, bone remodelling has bone resorption and formation phases tightly coupled. Interestingly, in these species, the bone loss in the second pregnancy and lactation measured with BMC and BMD is not as prominent as in the first lactation, but shows almost the same course, although the animals gave more milk in the second lactation. It seems that the organism adapts to the circumstances more easily in the second lactation compared to the first lactation in these two species.
 ...
PMID:Bone metabolism of milk goats and sheep during second pregnancy and lactation in comparison to first lactation. 1751 43

Little is known about the magnitude of vitamin D deficiency in patients with stage 5 chronic kidney disease (CKD-5) on hemodialysis (HD). In the present study, we examined the prevalence of vitamin D deficiency in patients with CKD-5 undergoing HD, evaluating the relationship between calcidiol levels with other parameters of mineral metabolism, nutrition/inflammation, functional capacity (FC), and sunlight exposure. Serum 25(OH) vitamin D levels were evaluated in 84 stable patients on chronic HD not receiving vitamin D supplements, with a mean age 58.9+/-16.6 years, during the month of September (end of winter in the southern hemisphere). 25(OH) vitamin D serum levels, intact PTH (iPTH), as well as serum albumin, calcium, phosphorus, and alkaline phosphatase were analyzed in fasting samples. Similarly, protein catabolic rate (PCR) and body mass index (BMI) were determined as nutritional parameters. Functional capacity according to the Karnofsky index, and sunlight exposure were also analyzed. In this study, we considered adequate vitamin D levels those above 30 ng/mL (U.S.A. National Kidney Foundation DOQI Guidelines), vitamin D insufficiency when levels were between 15 and 30 ng/mL, and vitamin D deficiency when levels were below 15 ng/mL. The mean 25(OH) D levels were significantly higher in men than in women (28.6 vs. 18.9 ng/mL; p=0.001). Vitamin D insufficiency was found in 53.5% of the patients (n=45) and vitamin D deficiency in 22.6% (n=19). In the univariate analysis, there were no correlations between 25(OH) D levels with age, iPTH, calcium, or phosphorus. There were positive correlations between serum 25(OH) D levels and degrees of sunlight exposure (R=0.55; p<0.0001), serum creatinine (r=0.38; p<0.001), serum albumin (r=0.22; p=0.04), and a negative correlation with BMI (r=-0.26; p=0.01). In the multiple regression analysis, only sunlight exposure (B=0.361), BMI (B=-0.23), and gender (B=-0.27) were significantly associated with 25(OH) D levels. Patients with FC 1 to FC 2 (n: 70%, 83.3%) had significantly higher 25(OH) D serum levels compared with FC 3 to FC 4 patients (n: 14%, 16.6%): 25.9 vs. 17.1 ng/mL (p=0.03). These results indicate that vitamin D insufficiency/deficiency is highly prevalent (76.1%) at the end of winter, in stage 5 CKD patients on HD, and lower values seem to be related to decreased sunlight exposure, female gender, increased BMI, and worse functional class.
 ...
PMID:Prevalence of 25(OH) vitamin D insufficiency and deficiency in chronic kidney disease stage 5 patients on hemodialysis. 1757 96

The Hungry Bone Syndrome (HBS) represents an important cause of prolonged hypocalcemia after parathyreoidectomy (PTX) due to primary, secondary or tertiary hyperparathyreoidism. The sudden postoperative withdrawal of parathyroid hormone (PTH) induces a stop in osteoclastic bone resorption without affecting the osteoblastic activity. Consequently, an increased bone uptake of calcium, phosphate and magnesium is observed. Risk factors for the development of HBS include: Large parathyroid adenomas, age > 60 years, high preoperative levels of serum PTH, calcium and alkaline phosphatase. In these patients a careful monitoring of clinical symptoms of hypocalcemia as well as the laboratory parameters are warranted during the immediate postoperative period. Treatment with oral calcium, and especially in patients with renal failure, additionally active vitamin D should be started as soon as possible after PTX. In severe cases of HBS, the administration of intravenous calcium is necessary. The duration of therapy is governed by symptoms and severity of the HBS and may last for up to 12 or more months. While prevention of HBS in high risk patients includes preoperative Vitamin D, the role of bisphosphonates has yet to be established.
 ...
PMID:[The hungry bone syndrome--an update]. 1768 87

The purpose of this study was to investigate the effect of the nonsteroidal anti-inflammatory drug carprofen on bone turnover and to monitor the progress of chronic osteoarthritic dogs by measuring different bone markers and radiographic evalutation of the corresponding joints. For this purpose 20 dogs of different ages and weight were devided into 2 groups. Ten dogs were assigned to Group R, treated with carprofen, and ten dogs to Group C, which had no treatment. Radiographs of the affected joints were reviewed initially and six months later at the end of the experiment. Blood was taken 8 times from each dog. Four bone markers (Osteocalcin (OC), bone-specific alkaline phosphatase (bAP), carboxyterminal telopeptide of type I collagen (ICTP), serum CrossLaps (CTX) as well as 1,25-(OH)2-Vitamin D and parathyroid hormone (PTH) were monitored for 6 months. No significant group effects on bone markers were notied. In Group R a decrease in ICTP concentrations during the first three months and a significant decrease in CTX concentrations in the first two months of the study were observed. The bone formation marker bAP revealed a significant decrease throughout the experiment. Three dogs of Group C and one dog of Group R showed osteoarthritic progression in the radiographs. The significant decrease of CTX indicates that carprofentreatment could have a retarding effect on the progression of osteoarthritis. Radiological findings suggest that carprofen may delay osteophyte formation. The monitoring of focal metabolic processes as in bone of a osteoarthrotic joint is difficult, since the bone mass is very active and metabolic processes may have an influence on the monitoring.
 ...
PMID:The effect of carprofen on selected markers of bone metabolism in dogs with chronic osteoarthritis. 1780 15

Cultured human primary osteoblasts reproduce the phenotypic differentiation and maturation of cells in vivo. We have investigated the influence of three isoforms of transforming growth factor beta (TGF-beta1, TGF-beta2 and TGF-beta3), three fibroblast growth factors (FGF-2, FGF-4 and FGF-6) and the active metabolite of Vitamin D [1,25-(OH)(2)D3] on proliferation, alkaline phosphatase activity and mineralization of human osteoblasts during a period of 24 days of culture. TGF-beta isoforms and three FGFs examined have been proved to be inducers of osteoblasts proliferation (higher extent for TGF-beta and FGF-2) and inhibitors of alkaline phosphatase activity and osteoblasts mineralization. Combination of these growth factors with the active form of Vitamin D induced osteodifferentiation. In fact Vitamin D showed an additive effect on alkaline phosphatase activity and calcium content, induced by FGF-2 and TGF-beta in human osteoblast. These results highlight the potential of proliferating cytokines' combination with mineralizing agents for in vitro bone growth induction in bone tissue engineering.
 ...
PMID:Effect of different growth factors on human osteoblasts activities: a possible application in bone regeneration for tissue engineering. 1793 69


<< Previous 1 2 3 4 5 6 7 8 9 10