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)

We have investigated the early cellular events that take place during the change in lineage commitment from hypertrophic chondrocytes to osteoblast-like cells. We have induced this osteogenic differentiation by cutting through the hypertrophic cartilage of embryonic chick femurs and culturing the explants. Immunocytochemical characterization, [3H]thymidine pulse-chase labeling, in situ nick translation or end labeling of DNA breaks were combined with ultrastructural studies to characterize the changing pattern of differentiation. The first responses to the cutting, seen after 2 d, were upregulation of alkaline phosphatase activity, synthesis of type I collagen and single-stranded DNA breaks, probably indicating a metastable state. Associated with the change from chondrogenic to osteogenic commitment was an asymmetric cell division with diverging fates of the two daughter cells, where one daughter cell remained viable and the other one died. The available evidence suggests that the viable daughter cell then divided and generated osteogenic cells, while the other daughter cell died by apoptosis. The results suggest a new concept of how changes in lineage commitment of differentiated cells may occur. The concepts also reconcile previously opposing views of the fate of the hypertrophic chondrocyte.
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PMID:Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. 759 73

Estrogen has been shown to modify calcium and skeletal homeostasis. In this study, we tested the ability of estrogen to influence the effects of short-term 1,25(OH)2D administration on biochemical indices of bone formation and resorption in a cross-sectional analysis of untreated (n = 10) and estrogen-treated (n = 14) osteoporotic women. Patients were given oral 1,25(OH)2D (Rocaltrol) 0.5 microgram twice a day for 5 days. Serum and urine were sampled at baseline and then 1 h after the first daily Rocaltrol dose for the 5 days of the study. 1,25(OH)2D levels rose similarly in both groups with plateaus reached by the third day of the investigation. Serum PTH levels decreased by the first sampling period (1 h after first Rocaltrol dose; p < 0.008 both groups) and continued to fall gradually in both groups. There were no changes in serum calcium but serum phosphorus rose by the second day (p < 0.05 both groups) and remained elevated throughout the remainder of the protocol. Serum bone Gla protein increased approximately 40% (p < 0.05) with no group differences. In contrast, total alkaline phosphatase and carboxy-terminal propeptide of type I collagen did not increase in either group. Furthermore, there were no significant increments in any bone resorption indicators, including serum tartrate-resistant acid phosphatase and cross-linked carboxy-terminal telopeptide of type I collagen, as well as urine hydroxyproline and pyridinoline. Serum IGF-1 levels also remained unchanged in both groups. We conclude that oral 1,25(OH)2D administration decreased 1-84PTH levels, probably due to a suppression of parathyroid production, and did not stimulate bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral 1,25-dihydroxyvitamin D administration in osteoporotic women: effects of estrogen therapy. 761 Sep 30

We describe the synthesis of a new, porous, modified bioactive glass for use as a template for bone formation in vitro. The porosity of the glass was 36.4%; the pore size ranged from 10-160 mm, and there was no incipient devitrification. Prior to seeding the glass with cells, it was necessary to condition the disks. Optimum conditioning was achieved by immersing the templates in a tris buffer at pH 6.8 for 48 h and then treating the glass with tissue culture medium for 1 h at 37 degrees C. The conditioned glass disks were seeded with 10(6) neonatal rat calvaria osteoblast-like cells; cells on the substrate were maintained in culture for 3-7 days. To prevent pH shifts due to corrosion of the conditioned glass, the medium:glass ratio was maintained at 90 ml/g. We found that the templates were rapidly invaded by cells which maintained the osteoblast phenotype; thus, they exhibited high alkaline phosphatase activity and synthesized type I collagen and osteocalcin. SEM-EDAX showed that the cells elaborated substantial amounts of extracellular matrix and a bonelike tissue was present throughout the entire template thickness. FTIR analysis of material formed in the glass indicated that the mineral phase was a biologic hydroxyapatite. Controls (cells without substrate and substrate without cells) exhibited none of these features. Results of the study suggest that this porous glass can function as a template for generating bone in vitro.
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PMID:Bioactive material template for in vitro synthesis of bone. 761 87

Bone sialoprotein (BSP) containing an Arg-Gly-Asp cell-binding sequence was purified from bovine bone 4 M guanidine-HCl extract after HCl demineralization by a series of chromatographic procedures. When this protein was coated on culture dishes in the presence of type I collagen, it increased both DNA content and alkaline phosphatase (ALP) activity in osteoblast-like MC3T3-E1 cells, and stimulated calcification in the cells, whereas fibronectin, another cell-binding protein, showed a marked increase in the DNA content but had little effect on the ALP activity. These findings suggest that BSP is mitogenic for preosteoblasts and differentiating the cells into osteoblasts, thereby stimulating bone calcification.
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PMID:Stimulation by bone sialoprotein of calcification in osteoblast-like MC3T3-E1 cells. 762 49

The effects of platelet-derived growth factor (PDGF) on DNA synthesis and mRNA expression of osteoblast markers in marrow stromal cells derived from adult (6 months) and old (24 months) rats were examined. Treatment of stromal cells from adult rats with dexamethasone induced the appearance of osteoblast-like cells. PDGF partially also inhibited the differentiation of stromal cells induced by dexamethasone. In cultures of serum-starved stromal cells, PDGF stimulated [3H]-thymidine incorporation into DNA in a dose-dependent manner with a maximum stimulation of 15-fold at 500 ng/ml. By comparison, insulin-like growth factor (IGF-I) has a small effect on [3H]-thymidine incorporation. The effect of PDGF and IGF-I on DNA synthesis was additive. Treatment of the confluent stromal cells from adult rats with PDGF increased the mRNA level of osteopontin fourfold without any significant effect on alkaline phosphatase and type I collagen mRNAs. In contrast, dexamethasone stimulated the mRNA expression of alkaline phosphatase, type I collagen, and osteopontin 2.1-, 2.3-, and 14-fold, respectively. Addition of PDGF to dexamethasone-treated cells failed to induce any further increase in osteopontin expression whereas the expression of alkaline phosphatase and type I collagen was partially reduced. The expression of osteocalcin mRNA was negligible in stromal cells but stimulated several fold by dexamethasone and 1,25(OH)2D3. PDGF inhibited drastically the elevation of osteocalcin mRNA. In contrast, IGF-I stimulated type I collagen expression 100% without any appreciable effect on the expression of osteopontin and alkaline phosphatase. The stimulatory effect of PDGF on osteopontin expression was augmented by IGF-I. Furthermore, PDGF attenuated the stimulatory effect of IGF-I on type I collagen expression. The responses of cultured cells from old rats to growth factors were also examined. PDGF or PDGF plus IGF-I increased [3H]-thymidine incorporation in stromal cells from old rats but to a lesser extent. However, PDGF was equally effective in stimulating osteopontin expression in cells from both adult and old rats. We concluded that PDGF is a potent mitogen but that the response of stromal cells from old rats is impaired. In addition, PDGF stimulates osteopontin expression in stromal cells and this effect is not age dependent.
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PMID:Effect of platelet-derived growth factor on DNA synthesis and gene expression in bone marrow stromal cells derived from adult and old rats. 762 82

Recently, the biochemical markers for bone metabolism have been developed and are expected to reflect the minor change of bone turnover. We compared bone formation markers: alkaline phosphatase-(Alp), bone gla-protein(BGP), carboxy-terminal propeptide of type I collagen(PICP); and bone resorption markers: carboxy-terminal telopeptide of type I collagen(ICTP), pyridinoline(Pyr), deoxypyridinoline(Dpyr) to see if they reflected the effects of aging and menopause in 95 premenopausal and 66 postmenopausal healthy subjects. We also compared the bone turnover in 29 vertebral osteoporosis patients. All markers except ICTP significantly increased with age in the healthy subjects. Alp, BGP, PICP, Pyr, and Dpyr were significantly higher in the postmenopausal group than in the premenopausal group. BGP, Pyr, and Dpyr in premenopausal subjects in their 50s were already significantly increased compared with BGP, Pyr, and Dpyr in premenopausal subjects in their 30s and 40s. To evaluate the discrimination power of the six markers in the postmenopausal subjects and in patients with osteoporosis, the z scores of six markers were calculated against the premenopausal group. z-scores of bone resorption markers(ICTP, Pyr, and Dpyr) were much higher than those of bone formation markers (Alp, BGP, and PICP) in patients with osteoporosis, even though z-scores of bone resorption markers were similar to those of bone formation markers in postmenopausal subjects. In conclusion, Alp, BGP, PICP, Pyr, and Dpyr had good performance in postmenopausal status. Resorption markers increased more than formation markers in osteoporosis subjects, and the bone turnover in osteoporosis subjects was more uncoupled than in postmenopausal subjects.
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PMID:Comparison of markers for bone formation and resorption in premenopausal and postmenopausal subjects, and osteoporosis patients. 762 40

The objective of this study was to determine the effect of oral contraceptive pills on bone turnover. The design consisted of a cross-sectional analysis of a prospective cohort. There were 52 women taking oral contraceptives and 156 nonuser controls from a large cohort of 1039 healthy women, aged 31-89 years (OFELY study). Most users were taking combined oral contraceptives containing 30 micrograms ethinyl estradiol and the mean duration of pill use was 6.7 +/- 6.4 years. Users and nonusers were matched for age [mean age (years): 39.3 +/- 3.5 vs. 40.5 +/- 4.3, range 35-49 years for both]. Main outcome measures included three markers of bone formation (serum osteocalcin, bone-specific alkaline phosphatase, and C-terminal propeptide of type I collagen) and two markers of bone resorption that are pyridinoline crosslinked peptides (Crosslaps and NTX). Users and nonusers did not differ for weight, height, alcohol and tobacco use, dietary calcium intake, parity, exercise activity, body fat and lean composition, and calcium chemistry tests. In pill users all bone formation and resorption markers were decreased compared with controls: osteocalcin, 7.7 +/- 2.7 vs. 10.1 +/- 3.1 ng/mL (-24%, p < 0.001); bone-specific alkaline phosphatase, 7.5 +/- 2.3 vs. 8.8 +/- 2.7 ng/mL (-15%, p < 0.003); C-terminal propeptide of type I collagen, 77.2 +/- 93.1 vs. 93.1 +/- 31.9 ng/mL (-17%, p = 0.001); Crosslaps: 175 +/- 91 vs. 211 +/- 105 micrograms/mmol Cr (-17%, p = 0.03); and NTX, 16.2 +/- 5.9 vs. 22.5 +/- 9.4 nmol of bone collagen equivalent/mmol Cr (-28%, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased bone turnover in oral contraceptive users. 765 64

To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 68 adults (25 females and 43 males) aged 22-61 (mean 44.2 +/- 1.2) years with GH deficiency (GHD) were studied. Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either GH in daily injections (0.125 IU.kg-1. week-1 for the first 4 weeks and subsequently 0.25 IU.kg-1. week-1) or placebo for 6 months. The trial continued as an open study with GH treatment for 6 to 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, cross-linked telopeptide of type I collagen and alkaline phosphatase activity), In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy. 765 42

We investigated the effect of recombinant human transforming growth factor beta 2 (rhTGF-beta 2) administration on trabecular bone loss induced by unloading in rats. Hind limb suspension for 14 d inhibited bone formation and induced osteopenia as shown by decreased bone volume, calcium and protein contents in long bone metaphysis. Systemic infusion of rhTFG-beta 2 (2 micrograms/kg per day) maintained normal bone formation rate, and prevented the decrease in bone volume, bone mineral content, trabecular thickness and number induced by unloading. In vitro analysis of tibial marrow stromal cells showed that rhTGF-beta 2 infusion in unloaded rats increased the proliferation of osteoblast precursor cells, but did not affect alkaline phosphatase activity or osteocalcin production. Northern blot analysis of RNA extracted from the femoral metaphysis showed that rhTGF-beta 2 infusion in unloaded rats increased steady-state levels of type I collagen mRNA but not alkaline phosphatase mRNA levels. rhTGF-beta 2 infusion at the dose used had no effect on metaphyseal bone volume and formation, osteoblast proliferation or collagen expression in control rats. The results show that systemic administration of rhTGF-beta 2 enhances osteoblast precursor cell proliferation and type I collagen expression by osteoblasts, and prevents the impaired bone formation and osteopenia induced by unloading.
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PMID:Systemic administration of transforming growth factor-beta 2 prevents the impaired bone formation and osteopenia induced by unloading in rats. 765 98

The toothless (tl) osteopetrotic mutation in the rat is characterized by generalized skeletal sclerosis, a severe reduction in the numbers of osteoclasts, monocytes, and macrophages, and absence of tooth eruption. Studies examining gene expression in bone-derived cells of tl rats and their normal littermates have shown that genes related to osteoblast function are aberrantly expressed in tl rats compared to normal littemates. We have previously shown that exogenous administration of colony stimulating factor-1 (CSF-1) to tl rats results in a dramatic reduction of the skeletal sclerosis and significant increases in the number of osteoclasts. Thus, we examined the effects of CSF-1 on osteoblast and osteoclast gene expression in tl rats as demonstrated by Northern blot analysis. While osteoblast-related gene expression as reflected by mRNA levels of alkaline phosphatase, osteocalcin, osteopontin, and type I collagen was normalized, osteoclast-related gene expression, as reflected by mRNA levels of carbonic anhydrase II and tartrate-resistant adenosine triphosphatase, remained significantly lower in CSF-1-treated tl rats compared to untreated normal littermates. Since previous studies have not demonstrated the CSF-1 receptor on osteoblasts, these results suggest that osteoblast abnormalities in tl rats are an effect of the osteopetrotic condition rather than the cause of the disease.
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PMID:Administration of colony stimulating factor-1 to toothless osteopetrotic rats normalizes osteoblast, but not osteoclast, gene expression. 766 37


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