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)

Bone sialoprotein (BSP) is a phosphorylated and sulfated glycoprotein that is a major noncollagenous protein of bone and other mineralizing connective tissues. BSP is characterized by the presence of several polyglutamic acid segments and an RGD motif that mediates cell attachment through a vitronectin-like receptor. Although the precise function of BSP is unknown, the expression of BSP in conjunction with bone formation in vitro indicates a role for this protein in the biomineralization of connective tissues. In this study we used Northern hybridization and in situ hybridization to determine the tissue-specific and developmental expression of BSP during embryogenesis and growth of rat tissues. Analysis of tissues obtained from 13, 17, and 21 day fetuses, and from 4-, 14-, and 100-day-old animals indicates that BSP mRNA expression is restricted to cells actively forming the mineralizing tissues of bone, dentin and cementum. BSP mRNA transcripts were first evident in fully differentiated osteoblasts of 17 day fetal tissues at sites of de novo intramembranous and endochondral bone formation, with maximal expression observed at 21 days of gestation. Thereafter, BSP mRNA levels decreased markedly, and in adult bone hybridization was detected only in the primary spongiosa of long bones. In comparison, mRNAs for osteopontin (OPN), alkaline phosphatase (ALP), and osteocalcin (OC) peaked at 4-14 days postpartum before declining. In the tibiae, Northern hybridization revealed a second peak of mRNA for BSP, ALP, and OPN at 14 days, reflecting an increased osteogenic activity due to the formation of the secondary centers of ossification in the epiphyseal cartilage. In situ hybridization also revealed BSP mRNA in hypertrophic chondrocytes at sites of bone formation, in odontoblasts of the incisor during dentinogenesis, and in cementoblasts during cementogenesis. In view of the restricted distribution and temporal changes in the expression of BSP mRNA that we observed together with the chemical properties of BSP, we believe that this protein has a specific role in mediating the initial stages of connective tissue mineralization.
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PMID:Development expression of bone sialoprotein mRNA in rat mineralized connective tissues. 144 13

The presence of proteins antigenically related to the GPIIb/IIIa complex expressed on platelets have been investigated on tissue macrophages recovered by bronchoalveolar lavage (lung alveolar macrophages, LAM) or peritoneal lavage (peritoneal macrophages, PM) as well as on monocytes. Polyclonal antibodies (pab) directed against human platelet GPIIb/IIIa and the vitronectin receptor (VnR), and mouse monoclonal antibodies (mab) against human GPIIb, GPIIIa or the GPIIb/IIIa-complex were used. Triton X-100 extracts of bronchoalveolar cells (BAC) (containing 94% LAM) and the ultrasedimentable fraction of cell-free bronchoalveolar lavage (US) reacted with the polyclonal antibodies against the GPIIb/IIIa-complex and the VnR, but only with one (P4) of the mabs. Cell microscopy after immunogold labelling and alkaline phosphatase immunostaining, as well as immunofluorescence using the P4 mab and the polyclonal anti-GPIIb/IIIa clearly demonstrated positive membrane staining of LAM, PM and monocytes. Both BAC and US extracts gave rise to immunoprecipitates in crossed and rocket immunoelectrophoresis using anti-GPIIb/IIIa and anti-VnR. Our data indicate that monocytes and their monocyte-derived tissue counterparts constitutively express GPIIb/IIIa-like antigen(s) on their membrane. The presence of such antigen(s) on tissue macrophages makes it unlikely that platelet contamination is responsible for these findings.
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PMID:Characterization of cytoadhesion molecules on human monocytes and tissue macrophages. 170 68

The multifunctional glycoprotein vitronectin, also called serum spreading factor and S-protein of complement, is a potent inducer of cell adhesion and spreading in vitro, and also has a regulatory function in the complement and coagulation pathways. It is present both in plasma and tissue. Recently, vitronectin immunoreactivity was demonstrated in the elastic fibres of normal human skin. Normal and amyloid kidney tissue was investigated for vitronectin immunoreactivity using polyclonal and monoclonal antibodies in an avidin-biotin-peroxidase complex technique and in an alkaline phosphatase anti-alkaline phosphatase complex technique. Vitronectin was found in the elastic layers of normal vessel walls, and in glomerular sclerotic lesions in cases of benign nephrosclerosis, but not in normal glomeruli. Strong specific vitronectin immunoreactivity was found in the amyloid deposits in kidneys from cases with amyloid A type amyloidosis, and in cases with amyloid light chain type amyloidosis. Structures immunostainable with anti-amyloid A antiserum were invariably immunostainable with anti-vitronectin. An antiserum against serum amyloid P component stained the same structures as did the anti-vitronectin antibodies, and in addition stained normal glomerular basement membranes. In conclusion, vitronectin immunoreactivity was demonstrated in elastic tissue, in amyloid deposits and in sclerotic lesions in human kidney.
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PMID:Immunohistochemical demonstration of vitronectin in association with elastin and amyloid deposits in human kidney. 244 39

Vitronectin, identical with serum-spreading factor and S-protein of complement, is a glycoprotein present in both plasma and tissue. It stimulates cell adhesion and spreading and affects the complement and coagulation pathways. Vitronectin immunoreactivity was recently found in conjunction with dermal and renal elastic fibres, in renal amyloid deposits in cases of AL- and AA-amyloidosis, and in sclerotic glomerular lesions. Skin specimens from lesions of patients with selected skin diseases were investigated with an avidin-biotin peroxidase technique using both monoclonal and polyclonal anti-vitronectin antibodies and an alkaline phosphatase anti-alkaline phosphatase technique using monoclonal anti-vitronectin antibodies. Vitronectin immunoreactivity was found in association with the abnormal elastic tissue in solar elastosis and pseudoxanthoma elasticum. It was also found in conjunction with dermal amyloid deposits in primary localized cutaneous amyloidosis and in Civatte bodies in cases of lichen ruber planus. In cases of erythropoietic protoporphyria and porphyria cutanea tarda, hyaline perivascular deposits also demonstrated positive vitronectin immunoreactivity. The presence of vitronectin immunoreactivity not only in normal and degenerated elastic fibres but also in various pathological tissue deposits suggests that vitronectin occurs both in elastic fibres and in different types of abnormal protein deposits.
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PMID:Immunohistochemical studies on vitronectin in elastic tissue disorders, cutaneous amyloidosis, lichen ruber planus and porphyria. 245 88

Recombinant human interleukin-1 beta, a mediator of osteoblastic cell function, was found to regulate the expression of the cell adhesion receptors, integrins, on human osteosarcoma cells. Interleukin-1 beta (IL-1 beta) at picomolar concentrations, specifically elevated approximately six- to tenfold the expression of the beta 1 subunit and its associated alpha subunits, but not the related vitronectin receptor, within 20 hours. Integrin beta 1 messenger RNA levels were elevated within 6 hours and peaked to tenfold higher levels after 20 hours exposure to IL-1 beta in two human osteosarcoma cell lines. The increase in the cell-surface beta 1 integrins resulted in a stronger binding of the IL-1 beta-treated cells to fibronectin. Cell growth was also inhibited by IL-1 beta, cell morphology was altered, and IL-1 beta-treated cells expressed an approximately two- to threefold higher alkaline phosphatase. This increase in alkaline phosphatase activity was found to be independent of the inhibition of cell proliferation. These data indicate that the beta 1 integrin family of cell surface receptors is a target for regulation by IL-1 beta, which also regulates cell proliferation and the expression of the osteoblastic phenotype in human osteosarcoma cells.
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PMID:Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin-1 beta in human osteosarcoma cells: inhibition of cell proliferation and stimulation of alkaline phosphatase activity. 252 62

The interactions of bone cells with their surrounding extracellular microenvironment may be mediated by integrins, a family of heterodimeric glycoproteins consisting of alpha and beta subunits that noncovalently interact to form cell-substratum adhesion receptors. We previously described the integrins on calvarial bone cells in rats with use of polyclonal antibodies against some integrin subunits. In the present study, we expanded this initial characterization by employing a more complete panel of monoclonal antibodies to identify integrins on human bone cells. Minced fragments of trabecular bone obtained during total knee arthroplasty were grown in culture until bone cells became confluent. The cells then were dissociated, plated again, grown to confluence, and assayed for alkaline phosphatase activity, response of cyclic adenosine monophosphate to stimulation with parathyroid hormone, and osteocalcin content. The percentage of the cells that adhered to various substrates was measured; 60-70% adhered to type-I collagen, fibronectin, vitronectin, and poly-D-lysine; 40-50% adhered to type-IV collagen, laminin, and gelatin; and only 10% adhered to fibrinogen. Flow cytometric analysis with anti-integrin monoclonal antibodies and sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitates of the human bone cells revealed high levels of alpha 1 beta 1, alpha 3 beta 1, alpha 5, beta 1 and alpha v beta 5 integrins and much lower levels of alpha 2 beta 1, alpha 4 beta 1, alpha v beta 1, and alpha v beta 3 integrins. This description of the integrin repertoire of cultured human bone cells represents the first step toward an understanding of the role played by integrins in the growth, maintenance, and repair of bone.
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PMID:Identification of integrin receptors on cultured human bone cells. 820 92

Ultrathin sections from the dermis of five normal subjects and from 10 patients suffering from pseudoxanthoma elasticum (PXE) were analyzed by immunoelectron microscopy with the aim of identifying and localizing proteins associated with the mineral precipitates within the altered elastic fibers. Serial sections were processed by indirect immunogold cytochemistry using primary antibodies against human fibronectin, vitronectin, bone sialoprotein, alkaline phosphatase, osteonectin, and osteopontin. In the latter two cases, antibodies against synthetic peptides were also used. The results indicate that normal elastic fibers contained osteopontin, and that this protein was associated with the apparently normal elastin as well as with the needle-shaped mineral precipitates in the elastic fibers of patients. On the contrary, significant amounts of vitronectin, alkaline phosphatase and, less, of bone sialoprotein were associated with the polymorphous mineral precipitates inside the elastic fibers. Large amounts of osteonectin and fibronectin, together with vitronectin, were localized on the microfilament aggregates, which were often associated with altered elastic fibers in PXE dermis and were never visualized in the dermis of control subjects. The results seem to indicate once more that PXE is a complex disorder of the fibroblast synthetic control. Elastic fiber mineralization might be considered a secondary event, which could depend on the abnormal synthesis and accumulation within the elastic fibers of proteins that are normally involved in mineralization processes.
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PMID:Matrix proteins with high affinity for calcium ions are associated with mineralization within the elastic fibers of pseudoxanthoma elasticum dermis. 857 19

In periodontal surgery, healing after guided tissue regeneration (GTR) may be explained by differences in functional activities of gingival and periodontal ligament fibroblasts (GF and PDLF). Several studies in vitro have supported this hypothesis, but much remains to be defined. In the present work, gingival and periodontal ligament fibroblasts derived from five healthy subjects were isolated and compared in vitro. The morphology of the cells was observed under scanning electron microscopy (SEM). Several extracellular matrix components (ECM) were studied to compare the effects on fibroblast attachment, proliferation, and protein synthesis. Several biochemical markers were examined in both cellular extract (CE) and conditioned medium (CM). We also examined the muscle differentiation markers alpha-smooth muscle actin, desmin, and smooth-muscle myosin. Finally, we studied the effects of epithelial cells on the proliferation and protein synthesis of the two types of fibroblasts. GF and PDLF appeared identical under the SEM. All ECM components enhanced attachment; however, while collagen types I and IV promoted the attachment of GF, gelatin, laminin, and vitronectin promoted that of PDLF. Most ECM components increased the proliferation rate of GF and the biosynthetic activity of PDLF. The biochemical markers were similarly distributed between the two cell types, except for alkaline phosphatase, which was detected only in the CE of PDLF. Both GF and PDLF strongly expressed alpha-smooth-muscle actin and were negative for desmin; only PDLF were positive for smooth-muscle myosin. Epithelial cells increased the proliferation of both GF and PDLF but had no effect on their biosynthetic activity. These in vitro results may better explain the in vivo functional differences between GF and PDLF.
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PMID:Functional characteristics of gingival and periodontal ligament fibroblasts. 867

To elucidate the reactions of bone around aseptically loosened total joint arthroplasties, 24 interface tissues with adjacent bone were obtained in 17 revision operations (11 hips and six knees). The morphology of the bone surface next to the interface membrane was investigated with histochemical and immunohistochemical techniques and then histomorphometrically analysed. One-third of the total bone surface. 32.69 +/- 5.16% (mean +/- SE) (n = 24), showed positive alkaline phosphatase activity. The bone surface in contact with the cells positive for CD11b (a macrophage marker) amounted to 19.33 +/- 5.16% (n = 24). The proportion of the osteoclastic bone resorption estimated by vitronectin receptor expression was 7.67 +/- 1.82% (n = 21). Tissues retrieved from the sites where radiographic evidence of osteolysis was present (n = 12) had a significantly larger extent of the bone surface in contact with CD11b-positive cells than did the tissues from areas without osteolysis (n = 12, p = 0.0067, Mann-Whitney U test), whereas no significant difference was observed in the extent of osteoclastic bone resorption. These data demonstrate that active bone formation, regarded as a repair process, is the most common feature even in revised cases. They also highlight the role played by macrophages, not as cells producing inflammatory mediators that could activate osteoclasts, but as cells primarily responsible for the bone loss in osteolytic lesions.
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PMID:Bone formation and bone resorption in failed total joint arthroplasties: histomorphometric analysis with histochemical and immunohistochemical technique. 867 61

Osteoclasts (OCs), which form by fusion of hematopoietic precursor cells, are typically present in large numbers in giant cell tumors of bone (GCTBs). These tumors may, therefore, contain cells which secrete factors that stimulate recruitment and differentiation of OC precursors. Multinucleated cells resembling OCs also form in cultures of human cord blood monocytes (CBMs) stimulated by 1.25 dihydroxyvitamin D3, but these cells lack the ability to form bone resorption pits, the defining functional characteristic of mature OCs. CBMs may thus require additional stimulation to form OCs; we therefore investigated whether GCTBs are a source of such a stimulus. CBMs were stimulated in long term (21 day) culture by medium conditioned by explants of GCTBs; media collected within 15 days of explant (early-CM) and after 15 days (late-CM) were employed. We also cocultured CBMs with primary GCTB-derived stromal cells as well as immortalized bone marrow stroma-derived cells. CBMs stimulated by early-CM formed resorption pits on cortical bone slices; however, stimulation by late-CM resulted in virtually no resorption. Both early-CM and late-CM increased CBM proliferation, but not the proportion of vitronectin receptor positive or multinucleated cells. Coculture of CBMs with stromal cells of GCTBs or bone marrow did not result in bone resorption, although these stromal cells (most expressing alkaline phosphatase but progressively losing parathyroid hormone receptor expression) expressed mRNA for cytokines involved in OC differentiation, including macrophage-CSF, granulocyte-macrophage-CSF, IL-11, IL-6, and stem cell factor. Our results indicate that CBMs are capable of terminal OC differentiation in vitro, a process requiring 1,25 dihydroxyvitamin D3 as well as diffusible factor(s) which can be derived from GCTB. Stromal cells of GCTB may produce such factors in vivo, but do not support OC differentiation in vitro, possibly through phenotypic instability in culture.
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PMID:Human cord blood monocytes undergo terminal osteoclast differentiation in vitro in the presence of culture medium conditioned by giant cell tumor of bone. 881 3


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