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 this study we asked whether members of the hedgehog gene family are involved in osteogenesis. C3H10T1/2 cells and MC3T3-E1 cells expressed the putative hedgehog receptor patched (Ptc) gene. Medium conditioned by chicken embryo fibroblast cultures expressing either Indian hedgehog or Sonic hedgehog stimulated alkaline phosphatase (APase) activity in cultures of the mouse mesenchymal cell line C3H10T1/2 and the osteoblastic cell line MC3T3-E1. These stimulatory effects were synergistically enhanced by bone morphogenetic protein-2 (BMP-2). Treatment with the amino-terminal portion of recombinant Sonic hedgehog proteins (rShh-N) up-regulated the expression of the Ptc gene within 12 h and increased production of APase in C3H10T1/2. rShh-N and BMP-2 also synergistically stimulated APase activity. rShh-N treatment did not affect the expression levels of Bmp-2, -4, -5, -6 and -7 genes. These findings indicate that hedgehog proteins directly act on osteogenic precursor cells and osteoblasts and stimulate osteogenic differentiation of these cells in co-operation with BMPs.
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PMID:Induction of osteogenic differentiation by hedgehog proteins. 926 35

An extensive literature on bone morphogenetic protein (BMP) induced generation and regeneration shows general agreement about one observation. The incidence and quantity of bone were greatest when BMP was delivered with a carrier of various biologic and non biologic polymers. In the present research, neutral lipids either endogenous in demineralized bone matrix (DBM) or exogenous in orign were employed as a delivery system for induced heterotopic bone formation in the rectus muscle in rats. Total neutral lipids including cholesterol were measured by correlated gravimetric and Sudan Black B dye binding methods. The heterotopic bone was measured by computer assisted radiomorphometric and histologic methods. Bone formation was measured by total calcium, DNA-P, and alkaline phosphatase activity. Composites of BMP and neutral lipids, separable from phospholipids by extraction with absolute acetone, were consistently osteoinductive. A significant quantity of the total bone lipid was closely associated with and extractable from the bone matrix non-collagenous protein fraction which had high levels of BMP activity. Lathyritic matrix was very low both in dye binding and osteoinductive activity. These observations suggest the possibility that lipids may serve as a BMP carrier in the process of induced bone development.
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PMID:Lipids closely associated with bone morphogenetic protein (BMP)--and induced heterotopic bone formation. With preliminary observations of deficiencies in lipid and osteoinduction in lathyrism in rats. 929 20

In this study, the phenotypic expression of osteoblast progenitor cells, 2T9, on characterized titanium surfaces was examined in the presence of a bone morphogenetic protein-2 (BMP-2). X-ray photoelectron spectroscopy spectra indicated the presence of titanium dioxide on titanium surfaces, along with surface contaminants such as carbon and nitrogen. In the in vitro study, the activity of BMP-2-treated osteoblast cells on titanium surfaces was marked by significantly higher alkaline phosphatase-specific activity and 1,25 (OH2) vitamin D3-stimulated osteocalcin production when compared to the untreated cells on titanium surfaces.
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PMID:Osteoblast responses to BMP-2-treated titanium in vitro. 933 26

The role of parathyroid hormone (PTH) upon osteo-/chondrogenic development was investigated in a bone morphogenetic protein (BMP)-dependent differentiation system involving the recombinant expression of BMPs in mesenchymal progenitor cells (C3H10T1/2). The constitutive expression of the PTH/PTH related protein receptor in this system led to a marked stimulation of chondrogenic and osteogenic development, while the permanent application of the ligand PTH(1-34) resulted in opposite responses by stimulating the early and suppressing the late stages of osteo-/chondrogenic development. These contrasting effects of PTH(1-34) on osteogenic and chondrocytic development seem, therefore, to depend on the cellular state of differentiation. The osteogenic and chondrocytic differentiation potential was substantiated histologically and by genetic analyses of marker genes like c-fos, alkaline phosphatase, osteocalcin, collagen alpha1(I), and collagen alpha1(II). The capacity to regulate osteogenic and chondrogenic development is located in the amino-terminal (1-34) region of the PTH molecule and seems to be mediated by the cyclic adenosine monophosphate signaling cascade. The application of other PTH domains like PTH(28-48) and PTH(53-84) did not exhibit significant responses. PTH acts as an essential factor in mesenchymal development controlling rates of differentiation into the osteogenic or chondrogenic lineage. The analysis of PTH effects in this system demonstrates the value of recombinant mesenchymal progenitor cells in the in vitro analysis of osteo-/chondrogenic development.
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PMID:Parathyroid hormone enhances early and suppresses late stages of osteogenic and chondrogenic development in a BMP-dependent mesenchymal differentiation system (C3H10T1/2). 942 Dec 32

To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II-expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II-expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II-expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.
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PMID:Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. 944 16

Subcutaneous implantation of bone morphogenetic protein (BMP) combined with a fibrous glass membrane (FGM) induces cartilage formation in the entire inner area of the membrane within 2 wk. It has been hypothesized that a tight FGM network (1 microm exclusion size) provides immature cells with spaces for penetrating into the membrane, but not for vascular formation, at least until 2 wk. To test this hypothesis, basic fibroblast growth factor (bFGF), known to be a potent stimulant of capillary formation, was applied to the implant. BMP was combined with FGM in the presence or absence of bFGF, and then implanted subcutaneously into the backs of rats. The bFGF-supplemented implant caused 1.3 times higher alkaline phosphatase activity and 3 times higher calcium contents at 2 wk, whereas type II collagen contents decreased, thus indicating that bFGF enhances bone formation in BMP/FGM implants. These results suggest that bFGF induces faster and stronger invasion of capillaries into the FGM and destroys its tight network, resulting in acceleration of the ossification process.
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PMID:Enhancement by bFGF of osteogenesis induced by rhBMP-2 in rats. 946 10

We previously showed that stromal cells derived from bone marrow specimens formed at the fracture site of human long bone differentiated during culture to polygonal cells and spindle cells, and polygonal cells, but not spindle cells, produced calcified matrix. To clarify the origin of polygonal and/or spindle cells, and factors necessary for differentiation of marrow stromal cells to osteogenic cells, we cultured stromal cells derived from the normal (unfractured) medullary cavity (SCN) as well as stromal cells from the medullary cavity distant from the fracture site (SCF). After 3 weeks of primary culture and 2 days of secondary culture, the cells were cultured in medium containing 1,25-dihydroxyvitamin D3 (VD), recombinant human bone morphogenetic protein-2 (BMP), or ipriflavone (IF) for 3 weeks. For biochemical analysis, cells reaching confluence after 3 weeks of secondary culture were cultured with one of the factors for 3 days. Some of SCF cultured with VD or IF were transformed to polygonal cells, and showed high alkaline phosphatase (ALPase) activity and high osteocalcin and insoluble calcium production. Cloned polygonal cells from the SCF formed nodules and aggregates consisting of calcium. Other SCF cultured with VD or IF and SCF cultured with BMP were spindle shaped. Some spindle-shaped cells from SCF cultured with BMP or IF revealed high ALPase activity and high osteocalcin production, comparable with the spindle cells from the fracture site. However, spindle-shaped cells from SCF cultured with VD and other spindle-shaped cells from SCF cultured with BMP or IF showed low ALPase activity and low osteocalcin production. The results show that SCF probably contain at least three subpopulations: (a) cells that differentiate to polygonal cells by the influence of VD or IF; (b) cells that differentiate to the spindle cells by the influence of BMP or IF; and (c) cells that are not transformed by the influence of VD, BMP, or IF.
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PMID:Culture of stromal cells derived from medullary cavity of human long bone in the presence of 1,25-dihydroxyvitamin D3, recombinant human bone morphogenetic protein-2, or ipriflavone. 951 17

Cartilage-derived morphogenetic proteins-1 and -2 (CDMP-1 and CDMP-2) are members of the bone morphogenetic protein (BMP) family, which play important roles in embryonic skeletal development. We studied the biological activities of recombinant CDMP-1 and CDMP-2 in chondrogenic and osteogenic differentiation and investigated their binding properties to type I and type II serine/threonine kinase receptors. In vivo, CDMP-1 and CDMP-2 were capable of inducing dose-dependently de novo cartilage and bone formation in an ectopic implantation assay. In vitro studies using primary chondrocyte cultures showed that both CDMP-1 and CDMP-2 stimulated equally de novo synthesis of proteoglycan aggrecan in a concentration-dependent manner. This activity was equipotent when compared with osteogenic protein-1 (OP-1). In contrast, CDMPs were less stimulatory than OP-1 in osteogenic differentiation as evaluated by alkaline phosphatase activity and expression levels of bone markers in ATDC5, ROB-C26, and MC3T3-E1 cells. CDMP-2 was the least osteogenic in these assays. Receptor binding studies of CDMP-1 and CDMP-2 revealed that both have affinity for the BMP receptor type IB (BMPR-IB) and BMPR-II, and weakly for BMPR-IA. Moreover, using a promoter/reporter construct, transcriptional activation signal was transduced by BMPR-IB in the presence of BMPR-II upon CDMP-1 and CDMP-2 binding. Our data show that distinct members of the BMP family differentially regulate the progression in the osteogenic lineage, and this may be due to their selective affinity for specific receptor complexes.
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PMID:Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis. 952 38

Direct cell-cell interactions are fundamental for tissue development and differentiation. We have studied the expression and function of cadherins in human osteoblasts during in vitro differentiation. Using reverse transcription-polymerase chain reaction and mRNA hybridization, we found that human trabecular bone osteoblasts (HOBs), osteoprogenitor marrow stromal cells (BMCs), and the osteogenic sarcoma lines, SaOS-2 and MG-63, expressed mRNA for cadherin-11 (C11) and N-cadherin (N-cad). HOBs and BMCs also expressed low levels of cadherin-4 (C4) mRNA. C11 was the most abundant cadherin protein present in human osteoblasts, and its expression was unaffected by bone morphogenetic protein-2 (BMP-2) treatment of either BMCs or HOBs. Likewise, N-cad mRNA did not change during BMP-2 incubation. Conversely, C4 protein, undetectable in transformed cell lines, was down-regulated by BMP-2 treatment of normal cells. Both C11 and C4 were localized to sites of cell-cell contact in both HOBs and BMCs, colocalized with beta-catenin, and bands corresponding to cadherins were coimmunoprecipitated by a beta-catenin antibody, findings indicative of functional cadherins. A decapeptide containing the HAV motif of human N-cad partially inhibited Ca2+-dependent cell-cell adhesion and completely prevented BMP-2-induced stimulation of alkaline phosphatase activity by BMCs. Thus, human osteoblasts and their progenitor cells express a repertoire of multiple cadherins. Cadherin-mediated cell-to-cell adhesion is critical for normal human osteoblast differentiation.
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PMID:Human osteoblasts express a repertoire of cadherins, which are critical for BMP-2-induced osteogenic differentiation. 955 63

Bovine brain microvessel pericytes, bone cells, and fibroblasts were grown in tissue culture in 3%, 21%, or 60% oxygen for 7 weeks. Alkaline phosphatase activity was highest in bone cells and pericytes grown in 3% oxygen, with the activity higher in the former than the latter. Alkaline phosphatase activity was very low in fibroblasts at every oxygen concentration. Osteocalcin concentration was higher in bone cells than in pericytes, was not detected in fibroblasts, and in bone cells and pericytes the concentration was highest in 21% oxygen. Other bovine brain microvessel pericytes were grown in 3% or 21% oxygen for 3 to 24 days in the presence or absence of bone morphogenetic protein 2 and in the presence or absence of parathyroid hormone. At Day 3 of culture, alkaline phosphatase activity was highest in 21% oxygen in the presence of bone morphogenetic protein 2. By Day 17 of culture, alkaline phosphatase activity was highest in 3% oxygen whether bone morphogenetic protein was present or not. Cyclic adenosine monophosphate production in pericytes in response to parathyroid hormone stimulation was very modest when compared with that of bone cells, and this response was not found to be significantly altered by bone morphogenetic protein 2, duration of culture, or the oxygen concentration during incubation. These findings show that the microvessel pericyte is capable of exhibiting several oxygen dependent, phenotypic characteristics ascribed to osteoblasts.
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PMID:Similarities in the phenotypic expression of pericytes and bone cells. 957 15


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