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)

In the accompanying study, we report an in vitro culture system from bovine bone cells that can be applied to investigate bone cell growth and differentiation. In this system, bovine bone cells placed in mineralization medium formed multilayers (days 2-3), began deposition of mineral (days 5-6), and eventually acquired a mineralized matrix sheet (days 14-20) through the stages of mineralizing nodules and trabecular-like structure. In the current study we used this system to investigate the relative expression of bone matrix genes that may play an important role in bone development and metabolism. alpha 1(I)-collagen, alkaline phosphatase, osteonectin, biglycan (PgI), decorin (PgII), osteopontin, and bone sialoprotein mRNA gene expression were measured on days 0, 2, 6, 10, and 20 (date when the cells were placed in mineralization medium as day 0). Total RNA was purified and analyzed by northern blot using radiolabeled cDNA encoding these genes. To comprehend the relationship between gene expression and mineralization, total calcium content in the cultures was also measured. During the culture period we observed several very different gene expression profiles. The expression of both alpha 1(I)-collagen and biglycan increased 3- to 4-fold by day 6 and then returned to basal levels by day 20. The osteonectin gene was highly expressed throughout the culture, with no significant increase in induction found during any time of culture. A significant induction of alkaline phosphatase (13.8-fold) gene expression was observed by day 6. Osteopontin showed a similar profile to that of alkaline phosphatase but had a much greater level of relative expression (26-fold) compared to day 0. Interestingly, downregulation during mineral accumulation seemed a common occurrence among many of the genes measured. In contrast, the bone sialoprotein gene showed a significant and distinct expression pattern, increasing rapidly after the onset of mineralization on day 6 and ultimately reaching 140-fold that of day 0. Decorin (Pg II) showed an increasing pattern, with the final relative level of induction 5-fold on day 20. These data suggest that the development of the mature osteoblastic phenotype, complete with the ability to produce a thick mineralized matrix, requires the differential regulation of a series of genes and their gene products over the culture period.
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PMID:Bone matrix mRNA expression in differentiating fetal bovine osteoblasts. 164 43

The non-collagen proteins of bone are a complex set of molecules that arise from local or exogenous sources. Because bone mineral is an excellent adsorbent, many circulatory and/or cell surface proteins bind to bone, where they may have immediate or subsequent effects. These include the alpha 2-HS-glycoprotein from blood and the potent growth factors TGF-beta, PDGF, IGF-1, FGF-a and -b, and IL-1, derived from both bone and non-bone cells. Furthermore, bone cell membrane proteins such as alkaline phosphatase may be cleaved from the cell surface and entrapped in the bone matrix. Bone is enriched in a variety of enzymes and their inhibitors by similar adsorption processes. Even osteocalcin, a bone cell product, is adsorbed to bone via mineral-binding (Gla) groups. The bone sialoproteins (BSP-I or osteopontin and BSP-II) also bind to the mineral via acidic groups. Because of this phenomenon it is difficult to distinguish whether a given protein's presence in bone is advantageous or merely fortuitous. The bone matrix proper consists of type I collagen and other osteoblast products such as osteonectin (a phosphorylated glycoprotein) and small proteoglycans (PG-I and/or PG-II) which are incorporated into bone collagen fibrils. These proteins may have additional roles in tissue morphogenesis and/or differentiation.
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PMID:Non-collagen proteins in bone. 306 9

The effects of retinoic acid (RA) on the expression of osteoblastic-related cell markers was examined. A marrow stromal osteogenic cell line, MBA-15, was analyzed by Northern blotting for the expression of bone matrix proteins. These cells constitutively express mRNA encoding for procollagen alpha 2 (I), osteonectin, osteopontin, biglycan, and alkaline phosphatase (ALK-P). Gene expression was unchanged in response to RA triggering for 24 hr. Furthermore, cell growth and enzymatic activities of ALK-P and neutral endopeptidase (CD10/NEP) were studied. These parameters were examined in MBA-15 and clonal populations representing different stages of differentiation. The cell's growth rate was unchanged, while ALK-P activity was greatly increased during the culture period under RA treatment in MBA-15 and in the clonal cell lines examined while CD10/NEP activity displayed a different pattern. MBA-15.4, a preosteoblast cell line, exhibited an inhibition in CD10/NEP activity at the beginning of the culture period, reaching basal level with time. This activity was greatly increased over control level in MBA-15.6, a mature stage of osteoblasts. Furthermore, the response of cell lines to various growth factors was tested subsequent to priming the cultures with RA. A synergistic effect was monitored for ALK-P activity in MBA-15.4 and MBA-15.6 cells under rh-bone morphogenic protein (BMP-2) and purified osteogenin (BMP-3), and an antagonist effect was measured when cells were exposed to transforming growth factor beta (TGF beta). Contrarily, BMP-2 and BMP-3 inhibited the CD10/NEP activity that had remained unchanged following priming of the cell with RA. Insulin-like growth factor I (IGF-I) and basic fibroblast growth factors (bFGF) did not affect either ALK-P nor CD10/NEP activities in both cloned cells. Cellular response to bone-seeking hormone, parathyroid hormone (PTH), and prostaglandin E2 (PGE2) was monitored by activation of intracellular cAMP. Treatment with RA caused a dramatic decrease in MBA-15.6 cell responses to PTH and PGE2, but no significant effects could be observed in other clonal lines.
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PMID:Differential effects of retinoic acid and growth factors on osteoblastic markers and CD10/NEP activity in stromal-derived osteoblasts. 752 53

We have established two clonal cell lines, designated SM1/9 and SM25/3 from the mandibular condyles of newborn BALB/c mice by immortalization with the SV40 large T antigen. These cells have a high proliferative activity and have been maintained in culture for over 50 passages. They are polygonal in shape. Electron microscopic studies indicate an immature phenotype for both clones and a lack of prominent intracellular filaments typical of fibroblasts. SM25/3 demonstrates different biological properties as compared to SM1/9, it is tumourigenic in nude mice, has a faster growth rate and exhibits less differentiated features. Both cell lines have low constitutive levels of alkaline phosphatase, and the activity of this enzyme is increased significantly in a dose and confluency dependent manner by retinoic acid and 1,25 (OH)2 vitamin D3. The cells express transcripts for retinoic acid receptors mRAR-alpha and mRAR-gamma but not for mRAR-beta. They also express mRNA for the 1,25 (OH)2 vitamin D3 receptor. They co-express transcripts for collagen types I, II, III. Expression of mRNA for extracellular matrix proteins such as biglycan, osteopontin, PAI-1 is detected. Cultured cells do not express mRNA for osteocalcin and this transcript is not inducible with 1,25 (OH)2 vitamin D3 or retinoic acid. Chondrocyte markers such as link protein and aggrecan are not detected. In vitro assays indicate that the cell lines have a limited capacity for osteogenic or chondrogenic differentiation. Similarly agarose culture experiments and extended treatment with retinoic acid indicate that they do not resemble dedifferentiated chondrocytes. Both the cell lines appear to express a phenotype intermediate to osteoblasts and chondroblasts and possibly represent transitional differentiation stages of the progenitor cells of the mandibular condyle. These cells could serve as useful models in elucidating the pathways of early mesenchymal cell differentiation.
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PMID:Establishment and characterization of two clonal cell lines derived from murine mandibular condyles. 757 May 75

The present study describes a new three-dimensional (3-D) culture system that enables the maintenance and phenotypic expression of bone marrow stromal osteoblasts. This culture substratum is advantageous in that it provides suitable conditions for attachment, growth, and differentiation of cells forming 3-D layers. The MBA-15 cell line was grown in unlimited quantities on 3-D Fibro-Cel carriers. These cells mineralized when exposed to ascorbic acid and beta-glycerophosphate (beta GP). Under these mineralization conditions, mRNA expressions of procollagen alpha 2(I) and [3H]-proline-labeled protein were increased. The expression of mRNA for osteonectin and to a lesser extent, for osteopontin was increased, whereas alkaline phosphatase and biglycan remained unaffected under similar conditions. Exposure of mineralizing cultures to dexamethasone reduced mRNA of procollagen alpha 2 (I) and osteonectin to control level. Scanning electron microscopy revealed that cells were grown along the fabric's fibers and produced collagen fibrils. Under appropriate conditions, extensive mineralization had taken place. The mineralization process involves the formation of calcospherites, and correlates with an increase in calcium content. The Fibro-Cel carriers enable formation of 3-D architecture and mineralized tissue in vitro.
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PMID:Mineralization of marrow-stromal osteoblasts MBA-15 on three-dimensional carriers. 795 77

To elucidate the characteristics of human periodontal ligament cells, we compared these cells with gingival fibroblasts isolated from the periodontal tissues of female human subjects. Human periodontal ligament (HPDL) cells had a sharper spindle shape and exhibited a higher growth rate than human gingival fibroblasts (HGF). HPDL cells had a high level of alkaline phosphatase (ALPase) activity, whereas HGF had a low level of such activity. Northern blot analysis demonstrated that HPDL cells produced ALPase mRNA. Decorin and biglycan mRNA were detected in both HPDL cells and HGF, whereas osteocalcin and bone sialoprotein mRNA was not detected in either cells. Both HPDL cells and HGF responded to prostaglandin E2 (PGE2) and isoproterenol, and produced cyclic AMP (cAMP), but did not respond to human 1-34 parathyroid hormone (PTH). Intracellular Ca2+ ([Ca2+]i) was measured in HPDL cells and HGF, using Fura 2-AM. Bradykinin (BK) and histamine (HIS), which are major chemical mediators, caused a transient rise of [Ca2+]i in the presence of extracellular Ca2+. In HGF, but not HPDL cells, HIS induced a biphasic transient peak in [Ca2+]i. BK and HIS increased PGE2 release in both HPDL cells and HGF. However, HGF released a larger amount of PGE2 than HPDL cells. These results demonstrate that HPDL cells have quite different characteristics from HGF. HPDL cells proliferate at a higher rate than HGF, show higher levels of cAMP production and greater ALPase activity, and respond in a different fashion to chemical mediators (BK and HIS) compared with HGF.
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PMID:Comparison of the characteristics of human gingival fibroblasts and periodontal ligament cells. 868 14

The pathogenesis of vitamin A-induced premature growth-plate closure was investigated in calves. A progressive increase in the severity of growth-plate lesions with time and a progressive increase in the extent of growth-plate involvement was observed. There was initial loss of metachromasia from the growth plate in a region that formed a narrow horizontal band of cartilage composed of the epiphyseal growth zone and a strip of reserve-zone cartilage. Immunostaining revealed there was loss of aggrecan, decorin, and biglycan from this region; however, it was doubtful that the regional loss of proteoglycan was a major contributing factor in the pathogenesis of premature growth-plate closure. This is because this region was the vestige of cartilage that remained when growth-plate closure was almost complete. The major alteration was premature mineralization of columnar cartilage and subsequent endochondral ossification. This caused the depth of the columnar zone to be reduced. Columnar-zone cartilage cells appeared immature where the matrix became mineralized and lacked the morphology of hypertrophic chondrocytes. The depth of the reserve-cartilage zone also was reduced as matrix mineralization of the columnar zone progressed, and further reduction in columnar cartilage depth occurred. Eventually, there was matrix mineralization within the adjacent reserve cartilage. The distribution of reaction product after immunostaining with antibodies to the following proteins was described during normal endochondral ossification: aggrecan, decorin, biglycan, versican, type I collagen propeptide, type I collagen, type II collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase. Biglycan, type I collagen propeptide, type I collagen, osteopontin, osteocalcin, osteonectin, bone sialoprotein, and alkaline phosphatase were localized within the cytoplasm or surrounding matrix of hypertrophic chondrocytes. In vitamin-treated calves, these same proteins were found in regions undergoing premature matrix mineralization even though the chondrocytes did not have a hypertrophic morphology. Therefore, vitamin treatment did not cause just a selective expression, but it caused expression of a large number of matrix proteins normally associated with the hypertrophic chondrocyte phenotype. Finally, completely mineralized columnar and reserve cartilage were removed by a modeling/remodeling process similar to that seen in the metaphysis.
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PMID:Pathogenesis of vitamin (A and D)-induced premature growth-plate closure in calves. 926 93

Elastin molecules aggregate in the extracellular space where they are crosslinked by stable desmosine bridges. The resulting polymer is structurally organized as branched fibers and lamellae, which, in skin, are wider (a few microns) in the deep dermis and become progressively thinner (fraction of a micron) towards the papillary dermis. Several general and local factors seem to regulate elastin gene expression, deposition and degradation. In skin, the volume density of the elastin network increases from birth up to maturity, when it accounts for about 3-4% of the tissue. However, its amount and distribution depend on dermis areas, which are different among subjects and change with age. Several matrix molecules (glycosaminoglycans, decorin, biglycan, osteopontin) have been found to be associated with elastin into the normal fiber, and several others have been recognized within pathologic elastic fiber (osteonectin, vitronectin, alkaline phosphatase in PXE). With age, and in some pathologic conditions, skin elastin may undergo irreversible structural and compositional changes, which seem to progress from localized deposition of osmiophilic materials to the substitution of the great majority of the amorphous elastin with interwoven filaments negative for elastin specific antibodies.
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PMID:Elastic fiber during development and aging. 929 92

We have examined the effects of BMP-2 on the expression of bone matrix proteins in both human bone marrow stromal cells (HBMSC) and human osteoblasts (HOB) and their proliferation and mineralization. Both HBMSC and HOB express BMP-2/-4 type I and type II receptors. Treatment of these two cell types with BMP-2 for 4 weeks in the presence of beta-glycerophosphate and ascorbic acid results in mineralization of their matrix. BMP-2 increases the mRNA level and activities of alkaline phosphatase and elevates the mRNA levels and protein synthesis of osteopontin, bone sialoprotein, osteocalcin, and alpha 1(I) collagen in both cell types. Whereas the mRNA level of decorin is increased, the mRNA concentration of biglycan is not altered by BMP-2. No effect on osteonectin is observed. The effect of BMP-2 on bone matrix protein expression is dose dependent from 25 to 100 ng/ml and is evident after 1-7 days treatment. In the presence of BMP-2, proliferation of HBMSC and HOB is decreased under either serum-free condition or in the presence of serum. Thus, BMP-2 has profound effects on the proliferation, expression of most of the bone matrix proteins and the mineralization of both relatively immature human bone marrow stromal preosteoblasts and mature human osteoblasts.
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PMID:Regulation of bone matrix protein expression and induction of differentiation of human osteoblasts and human bone marrow stromal cells by bone morphogenetic protein-2. 936 Nov 93

A male patient with abnormal postpubertal bone elongation was shown earlier to have a mutation in both alleles of the estrogen receptor, resulting in a nonfunctional gene. Marrow stromal fibroblasts (MSFs) derived from this patient were called HERKOs (human estrogen receptor knock outs), and in order to obtain continuous HERKO cell lines, they were immortalized using a recombinant adenovirus-origin-minus SV40 virus. MSFs are unique cells because they support hematopoesis and contain a mixed population of precursor cells for bone, cartilage, and fat. Three established cell lines (HERKO2, HERKO4, and HERKO7) were characterized and compared with the heterogeneous population of nonimmortalized HERKOs for their osteogenic potential. We performed Northern analysis of matrix genes implicated in bone development and metabolism and an in vivo bone formation assay by transplanting the cells subcutaneously into immunodeficient mice. All three HERKO lines expressed high amounts of collagen 1A1, osteopontin, osteonectin, fibronectin, decorin, biglycan, and alkaline phosphatase. Except for osteopontin, expression of these genes was slightly lower compared with nonimmortalized HERKOs. In the in vivo bone formation assay, the heterogeneous population of nonimmortalized HERKOs formed bone with high efficiency, while the HERKO lines induced a high-density, bone-like matrix. Finally, all HERKO cell types secreted high levels of insulin-like growth factor I and interleukin-6 into the culture medium relative to cells of normal human subjects. In summary, these lines of HERKO cells retain several of the phenotypic traits of MSFs after immortalization, including matrix and cytokine production, and provide a valuable source of a unique human material for future studies involving estrogen action in bone and bone marrow metabolism.
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PMID:Immortalization and characterization of bone marrow stromal fibroblasts from a patient with a loss of function mutation in the estrogen receptor-alpha gene. 955 60


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