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)

Bone tissue formation and the expression of osteoblast-specific genes were compared in vitro and in vivo for two well characterized murine clonal osteosarcoma cell lines (K7 and K8). In vitro studies were carried out under conditions that promoted extracellular matrix morphogenesis and mineralization. The K8 cells showed 8-fold greater alkaline phosphatase activity and mineral accumulation than did K7 cells during 21 days of in vitro growth. The K8 cell line showed high levels of bone sialoprotein (BSP), collagen type I (COL I), and alkaline phosphatase (APase) mRNA expression throughout its growth in vitro. In contrast, K7 cells showed an almost complete absence of BSP and COL I and very low levels of APase throughout the culture period. In vitro, both cell lines expressed very low levels of osteocalcin (OC). For in vivo studies, we used a three-dimensional culture device that permitted analysis of tissue formation by the cells after their implantation into syngeneic mice. The K8 cells consistently generated extensive mineralized woven bone after their subcutaneous implantation. The striking features distinguishing the bone formed by the implanted cells from normal recipient bone were the complete absence of osteoclasts or matrix resorption, the absence of OC protein, and very low levels of OC mRNA expression in the tissues formed by these cell lines. BSP, APase, and COL I expressions were maintained at high levels in the K8-produced tissues. In contrast to their near absence in vitro, APase, BSP, and COL I were expressed by K7 cells and increased with time in vivo. These findings demonstrate that the K7 cells in vitro are less differentiated than K8 cells, but that K7 cells in vivo undergo osteogenic maturation. Thus, expression of bone-specific genes in these osteogenic cell lines was dependent on systemic or local factors in recipient animals and was distinct for these cell lines when grown under in vitro conditions. OC protein does not appear to be needed for the mineralization of the extracellular matrix but may be needed to provide the necessary signals for the resorption and remodeling of the tissue.
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PMID:Osteogenic potential of murine osteosarcoma cells: comparison of bone-specific gene expression in in vitro and in vivo conditions. 864 85

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 brittleness of bone in people with lethal (type II) osteogenesis imperfecta, a heritable disorder caused by mutations in the type I collagen genes, arises from the deposition of abnormal collagen in the bone matrix. The inability of the abnormal collagen to participate in mineralization may be caused by its failure to interact with other bone proteins. Here, we have designed a strategy to isolate the genes important for mineralization of collagen during bone formation. Cells isolated from 16-day embryonic chick calvaria and seeded post-confluence in culture deposited a mineralized matrix over a period of 2 weeks. Chick skin fibroblasts seeded and cultured under the same conditions did not mineralize. Using RT-PCR, we prepared short cDNAs (approximately 300 bp) corresponding to the 3' ends of mRNA from fibroblasts and separately from the mineralizing calvarial cells. Subtractive cDNA hybridization generated a pool of cDNAs that were specific to mineralizing calvarial cells but not to fibroblasts. Screening of 100,000 plaques of a chick bone ZAP Express cDNA library with this pool of mineralizing-specific cDNAs identified ten clones which comprised full-length cDNAs for the bone proteins osteopontin (eight of the ten positives), bone sialoprotein II (one of the ten positives), and cystatin (one of the ten positives). cDNAs for type I collagen, fibronectin, alkaline phosphatase, house-keeping genes, and other genes expressed in fibroblasts were not identified in this preliminary screen. The pool of short cDNAs is likely to comprise cDNAs for further bone-specific genes and will be used to screen the entire bone cDNA library of 4.2 million clones.
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PMID:Tracing the pathway between mutation and phenotype in osteogenesis imperfecta: isolation of mineralization-specific genes. 872 4

It has been reported that periodontal ligament cells (PDLC) show osteoblastic phenotypes in culture. In most previous studies, PDLC have been obtained from the tooth root surface, however, a new method in which PDLC are obtained from the coagulum after tooth extraction has been proposed recently. To compare PDLC from tooth surface with these from coagulum, PDLC from both sources were cultured and examined. PDLC from both sources responded to PTH or PGE2 increasing cAMP and showed high alkaline phosphatase (ALP) activity. Some PDLC cultures produced mineralized tissues and these mineralizing cultures showed high ALP activity with high gene expression level of type I collagen, bone sialoprotein, and osteopontin in comparison with non-mineralizing cultures. PDLC from both sources expressed various osteoblastic or cementoblastic phenotypes and seemed to contain heterogenous mesenchymal cell population with various differentiation potentials. However, the frequency of cellular transmigration, rate of mineralized tissue formation, increased level of cAMP that responded to PTH or PGE2, and osteopontin expression pattern were different between PDLC from both sources. These differences indicate that PDLC cultures from coagulum contain more immature cells than PDLC from tooth surface.
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PMID:[Characterization of rat periodontal ligament cells in culture]. 874 17

Endochondral bone formation is one of the most extensively examined developmental sequences within vertebrates. This process involves the coordinated temporal/spatial differentiation of three separate tissues (cartilage, bone, and the vasculature) into a variety of complex structures. The differentiation of chondrocytes during this process is characterized by a progressive morphological change associated with the eventual hypertrophy of these cells. These cellular morphological changes are coordinated with proliferation, a columnar orientation of the cells, and the expression of unique phenotypic properties including type X collagen, high levels of bone, liver, and kidney alkaline phosphatase, and mineralization of the cartilage matrix. Several studies indicate that hypertrophic chondrocytes also express osteocalcin, osteopontin, and bone sialoprotein, three proteins which until very recently were widely believed to be restricted in their expression to osteoblasts. Recent studies suggest that the hypertrophic chondrocytes are regulated by the calcitropic hormones, morphogenic steroids, and local tissue factors. These considerations are based on the regulation by 1,25 (OH)2D3 and retinoids of the cartilage specific genes as well as osteopontin and osteocalcin expression in hypertrophic chondrocytes. They are also based on the effects on growth plate development caused by 1) transgenic ablation of autocrine/paracrine regulators such as PTHrP and of the transcriptional regulator c-fos and 2) naturally occurring genetic mutations of the FGF receptor. These studies further suggest that specific transcriptional factors mediate exogenous regulatory signals in a coordinated manner with the development of bone. While it has been widely demonstrated that the majority of hypertrophic chondrocytes undergo apoptosis during terminal stages of the developmental sequence, their response to specific exogenous regulatory signals and their expression of bone-specific proteins give rise to questions about whether all growth chondrocytes have the same developmental fates and have identical functions. Furthermore, specific questions arise as to whether there are similar mechanisms of regulation for commonly expressed genes found in both cartilage and bone or whether these genes have unique regulatory mechanisms in these different tissues. These recent findings suggest that hypertrophic chondrocytes are functionally coupled during endochondral bone formation to the recruitment of osteoblasts, vascular cells, and osteoclasts.
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PMID:Expression of bone-specific genes by hypertrophic chondrocytes: implication of the complex functions of the hypertrophic chondrocyte during endochondral bone development. 883 70

Bone morphogenetic proteins (BMPs) are a group of cytokines that are characterized by their ability to stimulate osteoblast differentiation and bone formation. However, the influence of BMPs on osteoblastic cells at different stages of differentiation is not known. Since bone matrix proteins are differentially regulated during bone formation we have studied the effects of recombinant human osteogenic protein-1 (rhOP-1; BMP-7) on the expression of these proteins by fetal rat calvarial cells (FRCCs) at discrete stages of osteoblast differentiation. Continuous administration of rhOP-1 to FRCCs, beginning at confluence (day 7), produced a dose-dependent increase in the number, size and mineralization of bone-like nodules formed in the presence of vitamin C and beta-glycerophosphate. Within 9 h of administration, rhOP-1 stimulated a 3-fold increase in OPN mRNA which was reflected in a comparable increase in the low phosphorylated, 55 kDa form of osteopontin. In contrast, changes in type 1 collagen, alkaline phosphatase and bone sialoprotein mRNAs followed the differentiation of preosteoblastic cells, and were increased 2-, 4- and 5-fold, respectively, after 8 days (day 15). When administered at intermediate stages of osteoblast differentiation (days 12, 15 and 18) BSP remained refractory to rhOP-1 whereas the ALP was increased almost 2-fold, independent of the constitutive levels of mRNA expression. To determine the effects on osteoblasts, FRCCs were first grown to the bone nodule-forming stage (day 21) before rhOP-1 was administered. Only modest, transient increases in the expression of ALP and OPN mRNAs were evident whereas OC expression was increased more than 3-fold. In contrast, collagen type 1 and BSP mRNA levels were not changed significantly. These results suggest that rhOP-1 increases bone formation by promoting osteoblastic differentiation, as indicated by the increased number of bone forming colonies and by increasing the number of osteoblastic cells in the colonies, but not by increasing matrix production by individual osteoblasts. It is also evident that the regulation of bone matrix proteins by rhOP-1 is dependent upon the differentiated state of the cell.
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PMID:Effects of osteogenic protein-1 (OP-1, BMP-7) on bone matrix protein expression by fetal rat calvarial cells are differentiation stage specific. 884 28

The efficacy of colchicine combined with ursodeoxycholic acid (UDCA) and UDCA alone in the treatment of patients with nonadvanced primary biliary cirrhosis (PBC) was evaluated in a 2-year controlled study. Seventy-four patients with PBC who had been treated previously with UDCA (at least 8 months) but still had abnormal liver test results, especially elevated alkaline phosphatase activity, were randomized to be administered colchicine (1 mg/d, 5 days per week) (n = 37) or a placebo (n = 37). In addition, the patients were treated with UDCA (13-15 mg x kg(-1) x day(-1)). The patients underwent clinical examination and liver tests every 6 months and upper endoscopy and liver biopsy at entry and at 2 years. Procollagen type III aminoterminal peptide (PIIINP), hyaluronic acid, and sulfobromophthalein (BSP) elimination kinetics were determined at entry and after 2 years. After 2 years of treatment, relative to UDCA, colchicine combined with UDCA did not significantly improve symptoms, laboratory findings (serum bilirubin level, alkaline phosphatase and alanine transaminase [ALT] activities, immunoglobulin [Ig] M level), serum markers of fibrosis, or histological features, except lobular inflammation. Colchicine did tend to slightly reduce the progression of esophageal varices; however, the difference was not significant. BSP elimination kinetics (45-minute retention percentage) was significantly improved when treated with colchicine. During the 2-year study, the only clinical complications were variceal bleeding in one patient administered colchicine and two administered the placebo. Two patients died from nonliver causes. One severe adverse effect (peripheral neuromyopathy) was observed in a colchicine-treated patient. In conclusion, this study suggests that colchicine appears to provide a slight advantage relative to UDCA alone in patients with nonadvanced PBC.
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PMID:A randomized trial comparing colchicine and ursodeoxycholic acid combination to ursodeoxycholic acid in primary biliary cirrhosis. UDCA-PBC Study Group. 890 82

Bone marrow stromal cells of femora from young adult rats produce bone-like mineralized tissue in culture. We evaluated three implant materials (hydroxyapatite (HA), glass-ceramics (GC) and commercial pure titanium (Ti)), as to their ability to provide an environment for marrow cells to differentiate into osteoblasts and function as suitable for mineralized tissue formation. We did this by measuring the DNA content, alkaline phosphatase (ALP) activity and calcium (Ca) content in culture, and the expression of osteopontin and bone sialoprotein by means of analysis of gene expression using Northern hybridization. DNA measurement showed no difference between each material, but ALP activity and Ca content in the culture on HA and GC were higher than on Ti and the control. An analysis of the gene expression revealed the highest expression of osteopontin and bone sialoprotein in the culture on HA. Mineralized nodule formation (both in area and number) was the most predominant on HA, followed by that on GC. These results showed that HA and GC provided a favourable situation for marrow cells to differentiate osteoblasts, resulting in a large amount of mineralized tissue formation on these surfaces. Present in vitro results could explain the rapid bone bonding of HA and GC in vivo.
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PMID:Evaluation of implant materials (hydroxyapatite, glass-ceramics, titanium) in rat bone marrow stromal cell culture. 896 43

We have determined the age-related changes in the growth characteristics and expression of the osteoblast phenotype in human calvaria osteoblastic cells in relation with histologic indices of bone formation during postnatal calvaria osteogenesis. Histomorphometric analysis of normal calvaria samples obtained from 36 children, aged 3 to 18 months, showed an age-related decrease in the extent of bone surface covered with osteoblasts and newly synthesized collagen, demonstrating a progressive decline in bone formation during postnatal calvaria osteogenesis. Immunohistochemical analysis showed expression of type I collagen, bone sialoprotein, and osteonectin in the matrix and osteoblasts, with no apparent age-related change during postnatal calvaria osteogenesis. Cells isolated from human calvaria displayed characteristics of the osteoblast phenotype including alkaline phosphatase (ALP) activity, osteocalcin (OC) production, expression of bone matrix proteins, and responsiveness to calciotropic hormones. The growth of human calvaria osteoblastic cells was high at 3 months of age and decreased with age, as assessed by (3H)-thymidine incorporation into DNA. Thus, the age-related decrease in bone formation is associated with a decline in osteoblastic cell proliferation during human calvaria osteogenesis. In contrast, ALP activity and OC production increased with age in basal conditions and in response to 1,25(OH)2 vitamin D3, suggesting a reciprocal relationship between cell growth and expression of phenotypic markers during human postnatal osteogenesis. Finally, we found that human calvaria osteoblastic cells isolated from young individuals with high bone formation activity in vivo and high growth potential in vitro had the ability to form calcified nodular bone-like structures in vitro in the presence of ascorbic acid and beta-glycerophosphate, providing a new model to study human osteogenesis in vitro.
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PMID:Age-related changes in bone formation, osteoblastic cell proliferation, and differentiation during postnatal osteogenesis in human calvaria. 901 61

Normal bone formation is a prolonged process that is carefully regulated and involves sequential expression of growth regulatory factors by osteoblasts as they proliferate and ultimately differentiate. Since this orderly sequence of gene expression by osteoblasts suggests a cascade effect, and BMP-2 is capable of initiating and maintaining this effect, we examined the effects of BMP-2 on expression of other BMPs and compared these effects with the expression pattern of bone cell differentiation marker genes in primary cultures of fetal rat calvarial (FRC) osteoblasts. To examine the gene expression profile during bone cell differentiation and bone formation, we also examined the effects of rBMP-2 on bone formation in vivo and in vitro. rBMP-2 stimulated bone formation on the periosteal surface of mice when 500 ng/day rBMP-2 was injected subctaneously. When rBMP-2 was added to primary cultures of FRC osteoblasts, it accelerated mineralized nodule formation in a time and concentration-dependent manner (10-40 ng/ml). rBMP-2 (40 ng/ml) enhanced BMP-3 and -4 mRNA expression during the mineralization phase of primary cultures of FRC osteoblasts. Enhancement of BMP-3 and -4 mRNA expression by rBMP-2 was associated with increased expression of bone cell differentiation marker genes, alkaline phosphatase (ALP), type I collagen, osteocalcin (OC), osteopontin (OP), and bone sialoprotein (BSP). These results suggest that BMP-2 enhances expression of other BMP genes during bone cell differentiation. BMP-2 may act in a paracrine fashion in concert with other BMPs it induces to stimulate bone cell differentiation and bone formation during remodeling.
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PMID:Bone morphogenetic protein 2 (BMP-2) enhances BMP-3, BMP-4, and bone cell differentiation marker gene expression during the induction of mineralized bone matrix formation in cultures of fetal rat calvarial osteoblasts. 906 67


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