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)

19-Nor-1,25-(OH)(2)D(2), an analog of 1,25-(OH)(2)D(3), is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)(2)D(2) is approximately 10 times less active than 1,25-(OH)(2)D(3) in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)(2)D(2) also could be less potent than 1,25-(OH)(2)D(3) on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-beta, an enhancer of 1,25-(OH)(2)D(3)-induced ALP activity in this cell line. Transforming growth factor-beta alone had no effect, whereas 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)(2)D(2) has the same potency as 1,25-(OH)(2)D(3) not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)(2)D(2) would have deleterious effects on bone remodeling.
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PMID:Relative potencies of 1,25-(OH)(2)D(3) and 19-Nor-1,25-(OH)(2)D(2) on inducing differentiation and markers of bone formation in MG-63 cells. 1142 75

Although osteoarthritis is characterized by a progressive loss of the extracellular cartilage matrix, very little is known about the fate of articular chondrocytes during the progression of the disease. In this study we examined the expression of syndecan-3, a marker of early chondrocyte differentiation, and annexin VI, a marker of late chondrocyte differentiation, in mammalian embryonic growth plate cartilage and normal and osteoarthritic human articular cartilage. Whereas syndecan-3 was expressed in the proliferative and hypertrophic zones of growth platecartilage, immunostaining for annexin VI waspredominately found in the hypertrophic and mineralizing zones of fetal bovine growth plate cartilage. Approximately 20% of chondrocytes were immunopositive for syndecan-3 in normal human articular cartilage, the number of syndecan-3-expressing chondrocytes significantly increased during the progression of osteoarthritis with more than 80% syndecan-3-positive cells in the upper zone of severely affected osteoarthritic cartilage. Similarly, the number of annexin VI-expressing cells significantly increased in the upper cartilage zones during the progression of osteoarthritis. Furthermore, immunostaining for proliferating cell nuclear antigen, a marker for cell proliferation, was detected in chondrocytes in the upper zone of osteoarthritic cartilage. Double-labeling experiments with antibodies against syndecan-3 and annexin VI revealed chondrocytes that expressed only syndecan-3, and cells that expressed both syndecan-3 and annexin VI. These results suggest that the expression of early (proliferating cell nuclear antigen, syndecan-3) and late differentiation markers (annexin VI, alkaline phosphatase) is activated in chondrocytes of osteoarthritic cartilage.
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PMID:Expression of early and late differentiation markers (proliferating cell nuclear antigen, syndecan-3, annexin VI, and alkaline phosphatase) by human osteoarthritic chondrocytes. 1169 38

Grafted periosteum is known to have potential for heterotopic bone formation by endochondral ossification. Although osteochondrogenic cells have been thought to originate from the osteogenic layer in grafted periosteum, no histological report has yet demonstrated this. The present study was designed to elucidate the origin of chondrogenesis preceding bone formation in grafted periosteum. Periostea harvested from young Japanese white rabbits' tibiae were grafted into suprahyoid muscles and examined radiographically and histologically at postoperative days 1, 7, 9, 14, 21, and 35. Normal periostea and tibial graft site were also examined. Surgical harvesting of the periosteum split and damaged its osteogenic layer but retained the fibrous layer intact. Most of the osteoblasts remained on the tibial bone surface, and only few cells of the osteogenic layer were present in grafted tissue. By the seventh day after grafting, the fibrous layer had thickened. The fibroblastic cells in the fibrous layer had significantly increased in number (P < 0.01) and were positively stained for proliferating cell nuclear antigen. These cells exhibited alkaline phosphatase activity at day 9. The differentiated chondrocytes had formed cartilage at postoperative day 14. Cells in the osteogenic layer appeared necrotic and subsequently disappeared. Following postoperative day 21, cartilage was replaced by trabecular bone. Bone formation was completed by 35 days. An X-ray analysis at this time also revealed new bone formation. These findings indicate that grafted periosteum forms bone by endochondral ossification and that the cells of the fibrous layer play essential roles in chondrogenesis that precedes such bone formation.
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PMID:Cellular origin of endochondral ossification from grafted periosteum. 1174 90

The role of Fos proteins in the regulation of germ cell progression during spermatogenesis has been studied in the frog, Rana esculenta. A peculiarity of this animal model is the finding of Fos in cytoplasmic compartment of primary spermatogonia during the resting period of the annual reproductive cycle. Interestingly, Fos is localized in the nuclear compartment when spermatogenesis resumes. Using Western blot analysis, we show that a 52-kDa Fos protein occurs in testicular cytosolic preparations, whereas two different Fos signals of 43 and 68 kDa are typical of the nuclear compartment. The 68-kDa Fos immunoreactive protein increases in nuclear extracts in concomitance with spermatogonia (SPG) proliferation either during the annual sexual cycle or in experimental animal groups where SPG proliferation was induced by thermal stimulus (24 C). Indeed, an increase in proliferating cell nuclear antigen was detectable after thermal induction of mitotic activity. A decrease in the 52-kDa signal and a concomitant increase in the 68-kDa signal is observed in testes of 24 C treated groups. The use of alkaline phosphatase and alkaline phosphatase inhibitors indicates that the 68-kDa protein is a phosphorylated form. Estrogens, which are able to induce SPG proliferation, are responsible for the appearance of the 43-kDa Fos form in nuclear testicular extracts. In conclusion, our results show, for the first time in a vertebrate species, that storage in the cytoplasm, on the one hand, and appearance as well as phosphorylation of Fos proteins in the nucleus of germ cells, on the other hand, regulate spermatogenesis progression during the seasonal breeding. Moreover, the phosphorylated 68-kDa Fos form may be involved in mechanisms underlying SPG proliferation.
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PMID:Cytoplasmic and nuclear Fos protein forms regulate resumption of spermatogenesis in the frog, Rana esculenta. 1175 5

The dura mater, the outermost layer of the meninges, is thought to be essential for calvarial morphogenesis, postnatal suture fusion, and osseous repair of calvarial defects. Despite numerous studies illustrating the fundamental role of the dura mater, there is little information about the autocrine and paracrine mechanisms regulating dural cell biology during calvarial ossification. Previous work conducted in the authors' laboratory demonstrated that non-suture-associated dural cells from 6-day-old rat pups expressed high levels of fibroblast growth factor 2 (FGF-2), whereas dural cells from 60-day-old adult rats expressed very little FGF-2. Because young mammals can successfully heal large calvarial defects, the authors sought to investigate the autocrine and/or paracrine effects of FGF-2 on the proliferation, gene expression, and alkaline phosphatase production of dural cells. Cultures of non-suture-associated dural cells were established from 6-day-old Sprague-Dawley rat pups and then stimulated with recombinant human FGF-2 (rhFGF-2; 10 ng/ml). Dural cells stimulated with rhFGF-2 proliferated significantly faster than untreated dural cells at 24 hours (2.1 x 10(5) +/- 3.2 x 10(4) versus 1.1 x 10(5) +/- 1.8 x 10(4), p < or = 0.001) and 48 hours (2.3 x 10(5) +/- 4.2 x 10(4) versus 1.2 x 10(5) +/- 1.3 x 10(4), p < or = 0.001). Moreover, dural cells stimulated with rhFGF-2 expressed 7-fold more proliferating cell nuclear antigen than did control cultures. Treatment with rhFGF-2 increased dural cell expression of genes important for skeletal repair: FGF-2 (7-fold), transforming growth factor beta 1 (3-fold), transforming growth factor beta 3 (4-fold), and type I collagen (4-fold). Furthermore, rhFGF-2 increased dural cell expression of osteopontin (2-fold), a "late" marker of osteoblastic differentiation. Interestingly, dural cell alkaline phosphatase activity, an "earlier" marker of osteoblast differentiation, was significantly decreased by treatment with rhFGF-2 compared with control cultures at 24 hours (0.005 +/- 0.001 versus 0.01 +/- 0.003, p < or = 0.01) and 48 hours (0.004 +/- 0.0009 versus 0.01 +/- 0.0009). Together these data provide insight into the autocrine and paracrine effects of FGF-2 on the biology of the dura mater.
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PMID:Dura mater biology: autocrine and paracrine effects of fibroblast growth factor 2. 1181 48

We identified genes responsive to sodium butyrate (SB) in colonic epithelial cells using cDNA microarrays. Treatment with 2 mM SB of colonic epithelial cells (MCE301), which was derived from transgenic mice harboring a temperature-sensitive simian virus 40 large T-antigen, arrested cell growth and showed a differentiated phenotype accompanying an increase in alkaline phosphatase activity. Of the approximately 900 genes analyzed, SB down-regulated 25 genes and up-regulated 88 genes by a factor of 2.0 or greater. Northern blot or TaqMan and Western blot analyses confirmed that the mRNA and protein levels of cyclin D1 and the level of proliferating cell nuclear antigen decreased, whereas the levels of integrin beta1 and osteopontin increased. The present results regarding the changes in gene expression, arrived at using microarrays, will provide a basis for a further understanding of the molecular mechanisms of cell growth arrest and differentiation in response to SB in colonic epithelial cells.
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PMID:Identification of genes responsive to sodium butyrate in colonic epithelial cells. 1205 16

Inhalation of silica leads to acute lung injury and alveolar type II cell proliferation. Type II cell proliferation after hyperoxic lung injury is regulated, in part, by parathyroid hormone-related protein (PTHrP). In this study, we investigated lung PTHrP and its effects on epithelial proliferation after injury induced by silica. Lung PTHrP decreased modestly 4 days after we instilled 10 mg of silica into rat lungs and then recovered from 4 to 28 days. The number of proliferating cell nuclear antigen (PCNA)-positive type II cells was increased threefold in silica-injured lungs compared with controls. Subsequently, rats were treated with four exogenous PTHrP peptides in the silica instillate, which were administered subcutaneously daily. One peptide, PTHrP-(38-64), had consistent and significant effects on cell proliferation. PTHrP-(38-64) increased the median number of PCNA-positive cells/field nearly fourfold above controls, 380 vs. 109 (P < 0.05). Thymidine incorporation was 2.5 times higher in type II cells isolated from rats treated with PTHrP-(38-64) compared with PBS. PTHrP-(38-64) significantly increased the number of cells expressing alkaline phosphatase, a type II cell marker. This study indicates that PTHrP-(38-64) stimulates type II cell growth and may have a role in lung repair in silica-injured rats.
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PMID:Parathyroid hormone-related protein-(38-64) regulates lung cell proliferation after silica injury. 1206 May 56

Endometrium consists of different cell populations such as epithelial and stromal cells and is mainly regulated by sex steroids. Isoflavones are plant-derived estrogenic compounds that have estrogenic and antiestrogenic properties in a cell-specific manner. We hypothesized that one of the potential health benefits of isoflavones may be their ability to regulate endometrial cell function. The present study was conducted to assess estrogenic and/or antiestrogenic effects of isoflavones (genistein, genistin, daidzein, and daidzin) in cultured human endometrial stromal and glandular (Ishikawa) cells by MTT colorimetric cell proliferation assay, proliferating cell nuclear antigen expression, and alkaline phosphatase activity assays. Experiments were performed in a time- (24-96 h) and concentration-dependent (10(-12) to 10(-5) M) manner. All isoflavones used in the present study induced endometrial stromal and Ishikawa cell proliferation when compared with control (vehicle) group in a time- (at 48 h and afterward) and concentration-dependent manner (at 10(-8) M and above) (P < 0.05). However, isoflavones (at 10(-8) and above concentrations) were also antiestrogenic when combined with estradiol (E(2)) (P < 0.05). The isoflavones revealed a weak estrogenic activity (39-67% less than E(2)) as assessed by alkaline phosphatase activity (P < 0.05), but when administered together with E(2), they antagonized estrogen induced alkaline phosphatase activity by 36-89% (P < 0.05). We conclude that, although isoflavones alone have weak estrogenic effects on endometrial stromal and glandular cells, in the presence of E(2) they act as antiestrogens.
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PMID:Estrogenicity of isoflavones on human endometrial stromal and glandular cells. 1246 50

To elucidate the sequence of early events in the increase in capillarity caused by reperfusion following transient coronary occlusion, the time course of expression of proliferating cell nuclear antigen (PCNA) was studied immunohistochemically in rat hearts subjected to different periods of reperfusion after a 3 minute occlusion. Twenty-one male Wistar rats were killed after different periods of reperfusion following occlusion of the coronary artery for 3 minutes. The left ventricles were removed and paired serial sections were treated immunohistochemically for PCNA or stained to show the enzymes characteristic of the arteriolar, intermediate and venular portions of the capillary bed. The time course of PCNA expression, and its distribution in relation to the different portions, was examined. An increase in PCNA-expressing nuclei was found at 24 hours after the start of reperfusion; numbers reached a maximum between 72 and 96 hours, and at 168 hours had decreased again. The majority of PCNA-expressing elements were localized to the dipeptidylpeptidase IV-reactive (i.e. venular) capillary portions, with some in the intermediate and alkaline phosphatase-reactive (i.e. arteriolar) portions. The distribution of PCNA in the early reperfusion period suggests that angiogenesis after transient ischemia occurs mainly from the venular side of the capillary bed, with some contribution from intermediate and arteriolar capillary portions.
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PMID:Coronary ischemia/reperfusion increases proliferating cell nuclear antigen in vascular endothelial cells in rat hearts. 1254 69

Indirect chronic electrical stimulation of skeletal muscle activates not only efferent but also afferent nerve fibres. To investigate effects specific to this on capillary growth, one of the earliest changes, cell proliferation and capillary ultrastructure were studied in ankle flexors of rats with and without deafferentation of the stimulated side. Two weeks after preganglionic section of dorsal roots L4-L6, the peroneal nerve was stimulated (10 Hz, 8 h day(-1)) for 2 or 7 days. Proliferating nuclei labelled by bromodeoxyuridine or proliferating cell nuclear antigen staining were colocalized to alkaline phosphatase-stained capillaries (Lc) or other interstitial nuclei (Li) in frozen sections of extensor digitorum longus. Capillary fine structure was examined in extensor hallucis proprius by transmission electron microscopy. The stimulation-induced increase in capillary and interstitial proliferation (Lc 9.9 +/- 1.9 %, Li 8.8 +/- 2.1 % vs. Lc 2.6 +/- 0.4 %, Li 1.9 +/- 0.3 % in controls, P < 0.05) was depressed at 2 days by dorsal root section (Lc 4.8 +/- 0.7 %, Li 3.2 +/- 0.9 %, P < 0.05), an effect likely to be mainly on fibroblasts; no depression was seen at 7 days. Dorsal root section reduced stimulation-induced capillary endothelial swelling at both time points. In contralateral muscles of intact rats, stimulation increased interstitial cell proliferation and capillary swelling, both effects being eliminated by dorsal root section. Capillary growth induced by stimulation (24 % increase in capillary : fibre ratio at 7 days) was unaffected by deafferentation. The reduction in capillary ultrastructural changes and interstitial proliferation in both stimulated and contralateral muscles implies that stimulation of afferent fibres leads directly to release of humoral factors and/or activation via dorsal roots of fibres that release humoral substances. Contralateral muscles are an inadequate control for the effects of chronic stimulation in the intact animal.
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PMID:The effect of chronic skeletal muscle stimulation on capillary growth in the rat: are sensory nerve fibres involved? 1256 6


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