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

---

Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteogenic protein-1 (OP-1 or bone morphogenetic protein-7 [BMP-7]) stimulates osteoblast differentiation in vitro and induces bone formation in vivo. BMPs exert their effects through complex formation with a heterodimeric receptor composed of a type I and a type II polypeptide. In the present study, mRNAs for three BMP subtype I receptors (ActR-I, BMPR-IA, and BMPR-IB) and one BMPR-II receptor were detected by Northern analysis in two human osteosarcoma cell lines (SaOS-2 and TE85) and in the primary cultures of fetal rat calvaria (FRC) cells. OP-1 affected the steady-state mRNA levels of these receptors differently among these cell types. To study the role of each receptor type in OP-1 action in FRC cells, receptor synthesis was inhibited by antisense oligonucleotides. Inhibition of receptor synthesis was confirmed by immunoprecipitation of radiolabeled cellular proteins with specific antibodies. The osteogenic action of OP-1 was measured by alkaline phosphatase (ALP) activity and mineralized bone nodule formation in FRC cells. Results showed that inhibition of synthesis of a single subtype I receptor alone did not affect significantly the OP-1-stimulated ALP activity. Inhibition of BMPR-II synthesis reduced the OP-1-stimulated ALP activity by about 50%. Inhibition of synthesis of any one of the type I receptor plus the BMPR-II receptor did not reduce the OP-1-stimulated ALP activity significantly beyond that observed by inhibition of BMPR-II alone. Under these conditions, nodule formation was affected similarly, thus supporting the observations made with the ALP measurements. The present results suggest that the ActR-I, BMPR-IA, and BMPR-IB receptors and the BMPR-II receptor are expressed and functional for OP-1 in FRC cells and that regulation of synthesis of these receptors may be a mechanism by which a specific cell type responds to OP-1. The turnover rate of these receptor proteins might be relatively long and another type II receptor(s) for OP-1 might be functional in FRC cells.
...
PMID:Inhibition of BMP receptor synthesis by antisense oligonucleotides attenuates OP-1 action in primary cultures of fetal rat calvaria cells. 984 5

To investigate the role of bone morphogenetic protein (BMP-2) in ossifying rat bone marrow stromal cell cultures, we determined the population of fibroblast-like stromal cells that expressed BMP-2 immunocytochemically (anti-rhBMP-2 monoclonal antibody), and compared that to alkaline phosphatase (AP) and collagen synthesis formed in culture over a 4-week period in control and dexamethasone-supplemented mineralizing media. In control media, the percentage of BMP-2-positive stromal cells (BMP-2(+)) increased from 12 to 25% within the first 4 days of culture. In mineralizing media, the level of BMP-2(+) cells was significantly increased (43-44%). The intensity of immunostaining gradually increased with time. The levels of AP were undetectable at 1 week in both control and mineralizing media, but increased gradually over the next 2 weeks and peaked at 3 weeks. ALP levels were significantly greater in cultures grown in mineralizing medium (P < 0.05 at 3 weeks, P < 0.01 at 4 weeks). Collagen synthesis peaked and was significantly greater at 3 weeks (P < 0.05) in cultures grown in mineralizing medium. The levels of AP and collagen synthesis most closely reflected the changes in the percentage of BMP-2(+) cells from 7 to 28 days. Though these changes may reflect a primary action of BMP-2 on marrow osteoprogenitor-like stromal cells, they do not exclude a mechanism that involves the induction of other members of the BMP family known to stimulate AP and collagen synthesis. We conclude that BMP-2 expression in cultures of fibroblast-like marrow stromal cells is enhanced when those cells are induced to become osteoblasts by exposure to dexamethasone.
...
PMID:Expression of BMP-2 by rat bone marrow stromal cells in culture. 986 86

Growth and differentiation factor 7(GDF7), also later called as bone morphogenetic protein (BMP)12, is a new member of the BMP superfamily, which induces formation of tendon-like tissue formation in the ectopic implantation experiments. We examined the effect of BMP12 on proliferation and expression of phenotype-related genes in rat osteoblastic osteosarcoma ROS17/2.8 cells. BMP12 treatment enhanced proliferation of ROS17/2.8 cells within 3 days and this effect was observed at least up to day 6 of the treatment. The cell number was increased by about 50% on day 3 and about two-fold by day 6. These effects were observed at the dose range between 40 and 1,000 ng/ml. Treatment with BMP12 also enhanced alkaline phosphatase activity by about 50% in ROS17/2.8 cells within 24 h of the treatment. The effect peaked at 48 h and was still observed at 72 h. The enhancing effect of BMP12 on alkaline phosphatase was observed similarly at the doses ranging from 40 to 1,000 ng/ml. These data indicate that BMP12 has positive effects on proliferation and phenotypic expression of ROS 17/2.8 cells.
...
PMID:Effects of GDF7/BMP12 on proliferation and alkaline phosphatase expression in rat osteoblastic osteosarcoma ROS 17/2.8 cells. 1002

In a search for therapeutic agents for the treatment of osteoporosis and bone fracture, we found that 2-benzothiopyran-1-carboxamide derivatives 1, derived from ipriflavone as a lead compound, increase cellular alkaline phosphatase activity in cultures of rat bone marrow stromal cells. Further modification of 1 has led to the discovery of more potent 3-benzothiepin-2-carboxamide derivatives 2. Of these, 3-benzothiepin derivatives bearing a 4-(dialkoxyphosphorylmethyl)phenyl group on the 2-carboxamide moiety such as 2h and 2q exhibited significant improvement of activity compared to ipriflavone. Asymmetric synthesis of 2h and 2q revealed that the (-)-isomers possessed activities superior to those of the (+)-isomers. Further evaluation of these compounds using the mouse osteoblastic cell line MC3T3-E1 revealed that (-)-2q enhanced the effect of bone morphogenetic protein. In addition, application of a sustained-release agent containing 2q increased the area of newly formed bone in a rat skull defect model. Based on these findings, (-)-2q was selected for further investigation as a new drug stimulating bone formation. Synthesis and structure-activity relationships for this novel series of 2-benzothiopyran and 3-benzothiepin derivatives are detailed.
...
PMID:Synthesis of novel 2-benzothiopyran and 3-benzothiepin derivatives and their stimulatory effect on bone formation. 1005 81

This study reports that recombinant adenovirus-mediated human bone morphogenetic protein-2 gene transfer can induce mesenchymal progenitor cell differentiation and bone formation. The recombinant adenovirus with the human bone morphogenetic protein-2 gene was constructed, and mature human bone morphogenetic protein-2 expression mediated by adenovirus gene transfer was detected by specific antibody. Under adenovirus-mediated bone morphogenetic-protein gene transfer, mesenchymal progenitor cell line C3H/10T 1/2 showed cell proliferation dependent on adenovirus bone morphogenetic-protein dose. The C3H/10T 1/2 cells transduced by adenovirus bone morphogenetic protein also exhibited differentiation to osteoblast phenotype, which indicates alkaline phosphatase activity. Injection of the C3H/10T 1/2 cells into the thigh muscles of nude mice led to ossicle development detectable on radiographs. Histological analysis indicated that the new ossicles that developed in the thigh muscles of the mice had different osseous components including bone trabeculae, bone marrow, and chondrified tissue. The results of this study demonstrate the potential for gene therapy by adenovirus-mediated bone morphogenetic-protein gene transfer.
...
PMID:Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo. 1007 46

The bone morphogenetic protein (BMP)-2 is a potent osteoinductive signal, inducing bone formation in vivo and osteoblast differentiation from non-osseous cells in vitro. The runt domain-related protein Cbfa1/PEBP2alphaA/AML-3 is a critical component of bone formation in vivo and transcriptional regulator of osteoblast differentiation. To investigate the relationship between the extracellular BMP-2 signal, Cbfa1, and osteogenesis, we examined expression of Cbfa1 and osteoblastic genes during the BMP-2 induced osteogenic transdifferentiation of the myoblastic cell line C2C12. BMP-2 treatment completely blocked myotube formation and transiently induced expression of Cbfa1 and the bone-related homeodomain protein Msx-2 concomitant with loss of the myoblast phenotype. While induction of collagen type I and alkaline phosphatase (AP) expression coincided with Cbfa1 expression, Cbfa1 mRNA was strikingly downregulated at the onset of expression of osteopontin (OPN) and osteocalcin (OCN) genes, reflecting the mature osteoblast phenotype. TGF-beta1 treatment effectively suppressed myogenesis and induced Cbfa1 expression but was insufficient to support osteoblast differentiation reflected by the absence of ALP, OPN, and OCN. We addressed whether induction of Cbfa1 in response to BMP-2 results in the transcriptional activation of the OC promoter which contains three enhancer Cbfa1 elements. Transfection studies show BMP-2 suppresses OC promoter activity in C2C12, but not in osteoblastic ROS 17/2.8 cells. Maximal suppression of OC promoter activity in response to BMP-2 requires sequences in the proximal promoter (up to nt -365) and may occur independent of the three Cbfa sites. Taken together, our results demonstrate a dissociation of Cbfa1 expression from development of the osteoblast phenotype. Our findings suggest that Cbfal may function transiently to divert a committed myoblast to a potentially osteogenic cell. However, other factors induced by BMP-2 appear to be necessary for complete expression of the osteoblast phenotype.
...
PMID:Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. 1008 30

A mixture of heparin-Sepharose-purified bovine bone morphogenetic protein and type I atellocollagen was implanted in the subcutaneous tissues of 4-week, 10-month and 18-month-old rats. The implants were removed at 7, 14 and 21 days after implantation. The effects of rat age on ectopic bone formation were evaluated on the explants using haematoxylin-eosin staining, morphometric analysis, alkaline phosphatase activity and calcium content determination, as well as immunohistochemical staining of type IV collagen present in the basement membrane of blood vessels. On day 14 and 21, bone was observed in 4-week and 10-month-old rats, but the amount of bone formed in the latter was less than in the 4-week-old rats. In 18-month-old rats, bone was first found focally in very limited regions of the explants on day 21 and the amount of bone was much less than in 4-week-old rats. At all periods, alkaline phosphatase activity was higher in younger rats. On day 7, there were more blood vessels in the explants of 4-week-old rats than in those of 10-month or 18-month-old rats. On day 14 and 21, more blood vessels were found in the central regions of the explants in 4-week-old rats than in the same regions in 10-month or 18-month-old rats. The findings in the present study indicate that the rate and quantity of ectopic bone formation are reduced in aged rats, and suggest that the difference in blood vessel distribution is related to this reduction in ectopic bone formation.
...
PMID:Age effects on ectopic bone formation induced by purified bone morphogenetic protein. 1010 99

To determine if bone morphogenetic protein-2 (BMP-2) can induce the endochondral maturation of resting zone (RC) chondrocytes, confluent fourth-passage cultures of these cells were pretreated for 24, 36, 48, 72, or 120 h with recombinant human BMP-2. At the end of pretreatment, the media were replaced with new media containing 10(-10)-10(-8) M 1,25-(OH)2D3 or 10(-9)-10(-7) M 24,25-(OH2)D3 and the cells incubated for an additional 24 h. This second treatment was chosen, because prior studies had shown that the more mature growth zone (GC) chondrocytes and RC cells respond to 1,25-(OH)2D3 and 24,25-(OH)2D3 in distinctly different ways with respect to the parameters examined. The effect of BMP-2 pretreatment on cell maturation was assessed by measuring alkaline phosphatase specific activity (ALPase). In addition, changes in matrix protein production were assessed by measuring collagen synthesis, as well as [35S]-sulfate incorporation into proteoglycans. When RC cells were pretreated for 72 or 120 h with BMP-2, treatment with 1,25-(OH)2D3 caused a dose-dependent increase in ALPase specific activity and collagen synthesis, with no effect on proteoglycan sulfation. RC cells pretreated with 1,25-(OH)2D3 responded like RC cells that had not received any pretreatment. RC cells normally respond to 24,25-(OH)2D3; however, RC cultures pretreated for 72 or 120 h with BMP-2 lost their responsiveness to 24,25-(OH)2D3. These results indicate that BMP-2 directly regulates the differentiation and maturation of RC chondrocytes into GC chondrocytes. These observations support the hypothesis that BMP-2 plays a significant role in regulating chondrocyte maturation during endochondral ossification.
...
PMID:Treatment of resting zone chondrocytes with bone morphogenetic protein-2 induces maturation into a phenotype characteristic of growth zone chondrocytes by downregulating responsiveness to 24,25(OH)2D3 and upregulating responsiveness to 1,25-(OH)2D3. 1022 93

While parathyroid hormone-related protein (PTHrP) has been characterized as an important negative regulator of chondrocyte maturation in the growth plate, the autocrine or paracrine factors that stimulate chondrocyte maturation are not well characterized. Cephalic sternal chondrocytes were isolated from 13-day embryos, and the role of bone morphogenetic protein-6 (BMP-6) as a positive regulator of chondrocyte maturation was examined in monolayer cultures. Progressive maturation, which was accelerated in the presence of ascorbate, occurred in the cultures. During maturation, the cultures expressed high levels of BMP-6 mRNA which preceded the induction of type X collagen mRNA. Treatment of the cultures with PTHrP (10(-7) M) at the time of plating completely abolished BMP-6 and type X collagen mRNA expression. Removal of PTHrP after 6 days was followed by the rapid (within 24 h) expression of BMP-6 and type X collagen mRNA, with BMP-6 again preceding type X collagen expression. The addition of exogenous BMP-6 (100 ng/ml) to the cultures accelerated the maturation process both in the presence and absence of ascorbate and resulted in the highest levels of type X collagen. When exogenous BMP-6 was added to PTHrP containing cultures, maturation occurred with the expression of high levels of type X collagen, despite the presence of PTHrP in the cultures. Furthermore, BMP-6 did not stimulate expression of its own mRNA in the PTHrP treated cultures, but it did stimulate the expression of Indian hedgehog (Ihh) mRNA. These latter findings suggest that while PTHrP directly inhibits BMP-6, it indirectly regulates Ihh expression through BMP-6. Other phenotypic changes associated with chondrocyte differentiation were also stimulated by BMP-6, including increased alkaline phosphatase activity and decreased proliferation. The results suggest that BMP-6 is an autocrine factor that initiates chondrocyte maturation and that PTHrP may prevent maturation by inhibiting the expression of BMP-6.
...
PMID:BMP-6 is an autocrine stimulator of chondrocyte differentiation. 1023 67

Heparan-like polymers derived from dextran, named RGTA, were shown to stimulate bone repair in different bone defect models. Like heparin and heparan sulfates, RGTA potentiate in vitro the biological activities of heparin-binding growth factors (HBGFs), such as fibroblast growth factor (FGF), by stabilizing them against denaturations and by enhancing their binding with cellular receptors. RGTA were postulated to stimulate bone healing by interacting with HBGFs released in the wound site and, subsequently, by promoting the proliferation and/or differentiation of cells implicated in this process. We examined the effects of RGTA alone and associated with HBGFs on MC3T3-E1 osteoblastic cell proliferation and differentiation. RGTA inhibited cell proliferation, as measured by [3H]-thymidine incorporation into DNA. They enhanced the inhibition of DNA synthesis caused by transforming growth factor-beta (TGF-beta1) and bone morphogenetic protein-2 (BMP-2). RGTA alone increased the alkaline phosphatase and parathyroid hormone-responsive adenylate cyclase activities in MC3T3. RGTA enhanced the stimulation of the alkaline phosphatase activity induced by BMP-2 and decreased or suppressed the inhibition caused by TGF-beta1 and FGF-2. Furthermore, RGTA increased the response to parathyroid hormone stimulated by BMP-2. In conclusion, RGTA stimulate the expression of osteoblast phenotype features alone or in association with HBGFs. The ability to promote the differentiation of bone-forming cells is a potential explanation of the stimulating effect of RGTA on bone repair.
...
PMID:Effects of heparan-like polymers associated with growth factors on osteoblast proliferation and phenotype expression. 1039 5


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---