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)

The effects of recombinant human bone morphogenetic protein 2 (rhBMP-2) on osteochondrogenesis were examined in high-density cultures of periosteum-derived cells, which have the potential to differentiate into bone and hypertrophic cartilage in vitro. Proliferation of these cells was inhibited by treatment with rhBMP-2. The time course for alkaline phosphatase (ALP) expression was shortened and the mineralization of the culture was increased by supplementation with rhBMP-2. These stimulatory effects of rhBMP-2 were observed at doses of 10-100 ng/m. Bone Gla protein (BGP) was immunocytochemically detectable earlier in the culture treated with rhBMP-2, and the BGP-positive layer of the rhBMP-2-treated cultures was thicker than that of the control cultures. On the other hand, there was no difference in uronic acid content or the time course of alpha 1(II) collagen mRNA expression between the rhBMP-2-treated and the control cultures. These results indicate that rhBMP-2 shortens the time course of osteogenesis and increases the amount of bone formation, whereas chondrogenesis remains unaffected.
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PMID:Bone morphogenetic protein 2 stimulates osteogenesis but does not affect chondrogenesis in osteochondrogenic differentiation of periosteum-derived cells. 797 2

Differentiation of hypertrophic chondrocytes to an osteoblast-like phenotype occurs in vivo in the hypertrophic cartilage of chick embryo tibiae underneath early or prospective periosteum and in cartilage around vascular canals. Synthesis of type I collagen by hypertrophic chondrocytes was shown by immunolocalization of the C propeptide. By enzyme cytochemistry it was instead shown that, in vivo, further differentiating hypertrophic chondrocytes express alkaline phosphatase at the time of initial mineral deposition. Evidence that hypertrophic chondrocytes may resume proliferation was obtained by BrdU labeling. A monoclonal antibody (LA5) was isolated and characterized that recognizes a hypertrophic chondrocyte membrane protein. In addition to staining hypertrophic chondrocytes surrounded by a type II and type X collagen-stainable matrix, the LA5 antibodies also stained elongated chondrocytes at the cartilage/bone collar interface and cells incorporated in the first layer of bone and osteoid matrix.
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PMID:Hypertrophic chondrocytes undergo further differentiation to osteoblast-like cells and participate in the initial bone formation in developing chick embryo. 797 6

We examined the effect of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human cultured osteoblastic cells established from human periosteum. The cells were cultured with varying concentrations of cytokines for three days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release from the osteoblastic cells. Any one of these cytokines did not influence the production of OC by the osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and promote bone resorption, while the effects of IL-6 on osteoblastic cells may be a little different from those of TNF-alpha or IL-1 beta. Cytokine-dependent these effects on the osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with rheumatoid arthritis.
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PMID:[Inhibitory effects of cytokines on human osteoblastic cells]. 802 Aug 64

To date, no histochemical data exist concerning the process of ossification of developing pedicles in deer. Four different zones of the growing pedicle (subcutaneous tissue; fibrous layer of the periosteum; cambial layer of the periosteum; woven bone of the primary spongiosa) were analysed in direct correlation to their histological appearance. The level of extractable specific alkaline phosphatase in the preosseous zones of the pedicle was 4-fold higher than levels in the epiphyseal growth plate previously reported. These results reflect that rapid bone formation takes place in the growing pedicle. Highest buffer-extractable alkaline phosphatase activity was found in the cambial layer directly in front of the mineralization area of the pedicle-bone, connected with maximal values for organically bound phosphate and inorganic phosphate. Moreover, the values for buffer-extractable alkaline phosphatase, organically bound phosphate and inorganic phosphate decreased with increasing mineralization in the zone of the primary spongiosa. The present histological and biochemical findings on the process of ossification in the pedicle show similarities to typical endochondral ossification. The process of pedicle growth may serve as a new and important system for chondrogenic and osteogenic studies, including a better understanding of antler development.
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PMID:Biochemical and histological study of the ossification in the early developing pedicle of the fallow deer (Dama dama). 805 32

In order to examine the effect of activin A on the process of bone formation, activin A was injected onto the periosteum of parietal bone in newborn rats, and the effect was compared with that of transforming growth factor (TGF)-beta. The daily periosteal injection of activin A increased the thickness of both the periosteal and bone matrix layers in a dose- and time-dependent manner. A maximal effect was obtained with 5.0 micrograms/day activin A. The time course of the effect of activin A on the periosteal thickness was similar to that of TGF-beta 1. However, the effect of TGF-beta 1 was much more pronounced and was mainly on fibroblasts and inflammatory cells. The time course of the effect of activin A on the thickness of bone matrix layer was different from that of TGF-beta 1. The effect of TGF-beta 1 reached maximum (1.8-fold) within 3 days, whereas that of activin A did not develop until day 6 and reached maximum at the end of the 12-day injection period (1.4-fold). Histological examinations revealed that both TGF-beta 1 and activin A increased the number of alkaline phosphatase-positive osteoblastic cells. These results demonstrate that periosteal injection of activin A stimulates bone formation. In addition, although the possibility cannot be ruled out that the dramatic effect of TGF-beta 1 on the periosteal layer might have affected the delivery of TGF-beta 1 to the bone surface, these observations also suggest that the mode of action of activin A may be different from that of TGF-beta 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of local injection of activin A on bone formation in newborn rats. 806 59

We examined the effect of TNF-alpha, IL-1 beta and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human osteoblastic cell cultures obtained from human periosteum. The cells were cultured with varying concentrations of cytokines for 3 days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release by osteoblastic cells. These cytokines did not influence the production of OC by osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and that the effects of IL-6 on osteoblastic cells may be different from those of TNF-alpha or IL-1 beta. These effects on osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with RA.
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PMID:Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells. 815 83

Four monoclonal antibodies (HOB-1-4) that react against human osteosarcoma cells (Saos-2) and human fetal osteoblasts in situ were developed by immunizing mice with Saos-2 cells. HOB-1 (IgG1, k) and HOB-2 (IgM, k) stain cytoplasmic antigens in Saos-2 cells, human authentic osteoblasts and occasional cells in liver, spleen and, in the instance of HOB-1, kidney and adrenal gland. On Western blotting of Saos-2 cell lysates, HOB-1 recognizes a single protein species of M(r) 59,000, while HOB-2 reacts with a different species of M(r) 57,000. HOB-3 (IgG1, k) stains a cell membrane associated antigen in Saos-2 cells and osteoblasts in situ. The reaction pattern of this antibody is virtually identical to that seen in alkaline phosphatase (ALP)-positive cells in all organs examined immunohistochemically, except for intestinal epithelium. Both immunoblotting and immunoprecipitation analyses confirm that the antigen detected by HOB-3 is ALP. HOB-4 (IgG1, k) reacts weakly against Saos-2 cells cultured under standard conditions, but strongly following the exposure of the cells to the secretory inhibitor monensin. On frozen section screening, this antibody reacts preferentially with the collagenous extracellular matrix not only of the periosteum but of other tissues and organs as well. The precise identity of the HOB-4 antigen remains to be established. We suggest that these four monoclonal reagents will be useful adjuncts in characterizing the osteoblastic phenotype.
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PMID:Monoclonal antibodies that recognize antigens in human osteosarcoma cells and normal fetal osteoblasts. 826 50

We characterized cells that express parathyroid hormone/parathyroid hormone related peptide (PTH/PTHrP) receptor mRNA in bones of fetal and postnatal rats by in situ hybridization. During endochondral development of fetal bones, PTH/PTHrP receptor transcripts were highly expressed both in maturing chondrocytes and in osteoblasts in the periosteum and ossification center, but not in fully hypertrophic chondrocytes. Similar to the localization in the fetal bones, PTH/PTHrP receptor mRNA expression was highly localized to maturing chondrocytes in the articular cartilage and growth plate, and to osteoblasts in the femur of young rats. In both young and fetal rats, transcripts for Type X collagen were localized to hypertrophic chondrocytes, mostly between chondrocytes and bone cells both of which express PTH/PTHrP receptor mRNA. Transcripts for PTH/PTHrP receptors and alkaline phosphatase co-localized in the bone of young rats, but they did not co-localize in fetal bones at the early stages of endochondral ossification. These results show that PTH/PTHrP receptor mRNA is expressed in a cell-type and stage-specific manner during skeletal development.
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PMID:In situ localization of PTH/PTHrP receptor mRNA in the bone of fetal and young rats. 839 66

Leukemia inhibitory factor (LIF) has been reported to affect bone metabolism, but results are variable. We examined the effect of mouse recombinant LIF on osteoclastic resorption in fetal bone explants representing different stages of osteoclast development. In cultures of 17-day-old fetal mouse metacarpals in which only osteoclast progenitors and precursors are present, resorption (measured as 45Ca release) was significantly inhibited to 29.2% and to 96.6% in the presence of LIF 100 and 1000 U/ml, respectively. Histologic examination of the explants treated with 1000 U/ml of LIF confirmed the biochemical findings and showed that osteoclast progenitors and precursors remained in the periosteum and did not invade the mineralized matrix. In metacarpals of older fetuses (18- and 19-day-old) in which the mineralized cartilage has been invaded by mature osteoclasts, the inhibition of resorption by LIF (1000 U/ml) was 87.9 and 74.7%, respectively, the latter being significantly less than the inhibition observed in 17-day-old metacarpal cultures. The inhibitory effect of LIF was absent during concurrent administration of PTH or 1,25-(OH)2D3 and could be reversed by PTH. In addition, LIF was found to inhibit growth, mineralization, and alkaline phosphatase activity in metacarpals independently of osteoclastic resorption. These results suggest that LIF affects the development rather than the activity of osteoclasts, probably through an effect on the osteogenic cells. LIF may be an important endogenous regulator of bone metabolism.
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PMID:Leukemia inhibitory factor inhibits osteoclastic resorption, growth, mineralization, and alkaline phosphatase activity in fetal mouse metacarpal bones in culture. 844 37

Endosteal bone surface cells were previously shown to be involved in the regulation of bone formation in humans. In this study, we have characterized the cells isolated from the endosteal bone surface in adult rats. Fragments of periosteum-free tibia were obtained from 4-, 6- and 9-month-old rats by collagenase digestion, and the phenotypic characteristics of the osteoblastic cells migrating from the endosteal bone surface were evaluated in culture. Endosteal bone surface cells present a strong alkaline phosphatase (ALP) activity as shown by cytochemistry and measured biochemically. The cells synthesize high levels of osteocalcin as measured by radioimmunoassay. Osteocalcin production was increased after stimulation with 10 nM 1,25 dihydroxyvitamin D (1,25(OH)2 D) and the response to 1,25(OH)2 D was similar at all ages. Endosteal cells from young adult rats (4 months old) but not from older rats (6 and 9 months old) showed increased cAMP production in response to 10 nM parathyroid hormone (PTH), suggesting an age-related decrease in the PTH-responsiveness of the bone surface cells. Immunocytochemistry using specific antibodies showed that preconfluent endosteal bone cells from adult rats expressed collagen and noncollagenous bone proteins in culture in the absence of inducers. The cells synthesized mostly type-I collagen which remained localized intracellularly. Type-III collagen was only expressed at low levels. The bone surface cells also expressed osteocalcin and bone sialoprotein, two markers of differentiated osteoblasts, as well as osteonectin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cells isolated from the endosteal bone surface of adult rats express differentiated osteoblastic characteristics in vitro. 847 7


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