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)

The organic material of our teeth consists of collagens and a number of calcium-binding phosphoproteins. Six of these phosphoproteins have recently been grouped in the family of the SIBLINGs (small integrin-binding ligand, N-linked glycoproteins), namely osteopontin, bone sialoprotein, dentin matrix protein (DMP1), dentin sialophosphoprotein (DSPP), matrix extracellular phosphoglycoprotein (MEPE) and enamelin. We prepared a cDNA library from rat incisors in order to identify the genes involved in tooth formation. The library was screened by subtractive hybridization with two probes; one specific for teeth, the other for bone. We found that the vast majority of the clones from our library were expressed at similar levels in bone and teeth, demonstrating the close relationship of the two tissues. Only 7% of all the clones were expressed in a tooth-specific fashion. These included clones for the enamel proteins; amelotin, amelogenin, ameloblastin and enamelin; for the dentin proteins DSPP and DMP1; and for the intermediate filament protein cytokeratin 13. Several typical bone proteins, including collagen I, osteocalcin, alkaline phosphatase and FATSO, were also expressed at significantly higher levels in teeth than in bone, probably due to the extreme growth rate of rat incisors. The amino acid sequence of rat amelotin showed 62% identity with the sequence from humans. It was expressed considerably later than the other enamel proteins, suggesting that amelotin may serve a function different from those of amelogenin, ameloblastin and enamelin.
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PMID:Expression of phosphoproteins and amelotin in teeth. 1714 47

Tissue engineering approaches for bone blocks previously have used synthetic scaffolds. Bone graft (allograft) is used to fill bone defects, but standard processing can lessen this scaffold's osteoinductive potential. We wanted to test if allografts could be used to produce a viable bone block using mesenchymal stem cells. We hypothesized that mesenchymal stem cells differentiate into osteoblasts producing extracellular matrix when cultured on allografts. We also hypothesized that the addition of osteogenic supplements would increase the rate of differentiation. To test these hypotheses, mesenchymal stem cells were isolated from bone marrow aspirated from 10 patients and cultured on allografts from five donors (Group 2), producing 50 samples. This was repeated on allografts heat-treated to denature bioactive proteins (Group 1), and repeated again on allografts to which osteogenic supplements (Group 3) were added. Group 2 mesenchymal stem cells differentiated into osteoblasts producing higher levels of alkaline phosphatase, osteopontin, and Type I collagen matrix protein than Group 1. The rate of differentiation of Group 3 mesenchymal stem cells increased with the supplements. Overall, it was established that the bioactive proteins in the allograft stimulated mesenchymal stem cell differentiation into osteoblasts, with production of extracellular matrix, and that this differentiation increased with the addition of osteogenic supplements.
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PMID:Will mesenchymal stem cells differentiate into osteoblasts on allograft? 1714 67

Bone histology of distal renal tubular acidosis patients showed decreased bone formation with impaired bone matrix mineralization that is not entirely explained by an alteration in the mineral balance. Data from in vitro studies suggests a direct inhibitory effect of metabolic acidosis on osteoblast function. We investigated the effects of chronic metabolic acidosis on osteoblast differentiation from mesenchymal stem cells (MSCs). Human MSCs were allowed to differentiate into osteoblasts in culture. Concentrated hydrochloric acid was added to the medium to lower the bicarbonate concentration and pH. The expression of various osteoblastic genes and proteins and bone matrix mineralization were examined. Chronic metabolic acidosis enhanced the messenger RNA (mRNA) and protein expression of early osteoblast transcription factor, runx-2, whereas inhibiting osterix and having no effect on ATF-4. The expression of type I collagen, the most abundant bone matrix protein, was increased following the same pattern of runx-2. Likewise, metabolic acidosis slightly enhanced the expression of mature osteoblastic gene, osteocalcin. Study on mineralization revealed suppressed alkaline phosphatase mRNA and enzyme activity. Despite the augmented collagen deposit in acidic culture, bone matrix mineralization was impaired. In conclusion, chronic metabolic acidosis alters osteoblast differentiation from MSCs through its diverse effect on osteoblastic genes and proteins resulting in an impairment of bone formation.
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PMID:Chronic metabolic acidosis alters osteoblast differentiation from human mesenchymal stem cells. 1718 49

Genistein, a phytoestrogen, and zinc, an essential trace element, have an anabolic effect on bone components. We investigated whether the combination of genistein and zinc has additive and synergistic effects in osteoblastic cells in vitro. Osteoblastic MC3T3-E1 cells with subconfluency were cultured for 48 h in medium containing either vehicle, genistein (10(-6) or 10(-5) M), zinc sulfate (10(-5) or 10(-4) M) or genistein (10(-6) or 10(-5) M) plus zinc sulfate (10(-5) or 10(-4) M). The protein content in the osteoblastic cells was significantly increased in the presence of genistein (10(-5) M) or zinc (10(-4) M). This increase was significantly enhanced with a culture of genistein (10(-5) M) plus zinc (10(-4) M). The expression of mRNAs of alpha1(I) collagen and osteocalcin, which are bone matrix protein, in osteoblastic cells was demonstrated using reverse transcription-polymerase chain reaction (RT-PCR) analysis with a specific primer. This expression was not significantly increased with genistein (10(-6) or 10(-5) M) or zinc (10(-5) or 10(-4) M). The combination of genistein (10(-6) or 10(-5) M) and zinc (10(-5) or 10(-4) M) caused a significant increase in alpha1(I) collagen and osteocalcin mRNA expression in osteoblastic cells. Alkaline phosphatase mRNA expression in osteoblastic cells was significantly enhanced with a culture of genistein (10(-5) M) plus zinc (10(-4) M). The effect of genistein (10(-5) M) plus zinc (10(-4) M) in enhancing the expression of alpha1(I) collagen, alkaline phosphatase, or osteocalcin mRNAs in osteoblastic cells was completely prevented with a culture of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6-dichloro-1-beta-D-ribofuranosylbenimidazole (DRB) (10(-6) M), an inhibitor of transcriptional activity. Moreover, a culture with genistein (10(-5) M) or zinc (10(-4) M) for 14 or 21 days caused a significant increase in mineralization. This increase was markedly enhanced with a culture of the combination of genistein (10(-5) M) and zinc (10(-4) M). This study demonstrates that the combination of genistein and zinc can synergistically enhance gene expression and mineralization in osteoblastic cells.
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PMID:Genistein and zinc synergistically enhance gene expression and mineralization in osteoblastic MC3T3-E1 cells. 1720 94

The major non-collagenous proteins in dentin have extensive post-translational modifications (PTMs) that appear to be odontoblast-specific, so expression of recombinant dentin proteins in other cell types does not achieve the in vivo pattern of PTMs. We established cell lines from developing porcine dental papillae and used them to express recombinant dentin sialoprotein (DSP) and dentin matrix protein-1 (DMP1). Pulp cells were immortalized with pSV3-neo and clonally selected. Cell lines were characterized by reverse transcruption-polymerase chain reaction (RT-PCR) and assayed for alkaline phosphatase activity and mineralized nodule formation. One of the five cell lines (P4-2) exhibited an odontoblastic phenotype, as determined by expression of tooth-specific markers, response to cytokines, and ability to form mineralized nodules. DSP and DMP1 expression constructs were transiently transfected into various cell lines. DSP, expressed by P4-2 cells, contained chondroitin 6-sulfate, which is a defining modification of the DSP proteoglycan. DMP1 was secreted and cleaved by proteases, even in human kidney 293 cells, which normally do not express DMP1, demonstrating susceptibility to non-specific proteolysis. Both recombinant proteins enhanced P4-2 cell attachment in a dose-dependent manner. We conclude that we have immortalized porcine odontoblast-like cells which express recombinant dentin extracellular matrix components with post-translational modifications that closely resemble those produced in vivo.
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PMID:Establishment of porcine pulp-derived cell lines and expression of recombinant dentin sialoprotein and recombinant dentin matrix protein-1. 1730 16

Klotho-deficient mice exhibit multiple pathological conditions resembling human aging. Our previous study showed alterations in the distribution of osteocytes and in the bone matrix synthesis in klotho-deficient mice. Although the bone and tooth share morphological features such as mineralization processes and components of the extracellular matrix, little information is available on how klotho deletion influences tooth formation. The present study aimed to elucidate the altered histology of incisors of klotho-deficient mice-comparing the findings with those from their wild-type littermates, by using immunohistochemistry for alkaline phosphatase (ALP), osteopontin, and dentin matrix protein-1 (DMP-1), terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) detection for apoptosis, and electron probe microanalyzer (EPMA) analysis on calcium (Ca), phosphate (P), and magnesium (Mg). Klotho-deficient incisors exhibited disturbed layers of odontoblasts, predentin, and dentin, resulting in an obscure dentin-predentinal border at the labial region. Several odontoblast-like cells without ALP activity were embedded in the labial dentin matrix, and immunopositivity for DMP-1 and osteopontin was discernible in the matrix surrounding these embedded odontoblast-like cells. TUNEL detection demonstrated an apoptotic reaction in the embedded odontoblast-like cells and pulpal cells in the klotho-deficient mice. EPMA revealed lower concentrations of Ca, P, and Mg in the klotho-deficient dentin, except for the dentin around abnormal odontoblast-like cells. These findings suggest the involvement of the klotho gene in dentinogenesis and its mineralization.
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PMID:Involvement of the klotho protein in dentin formation and mineralization. 1808 32

For bone tissue engineering, it is important that mesenchymal stem cells (MSCs) differentiate into osteoblasts. To develop a method for differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) along the osteogenic lineage, we studied the effect of polyamines, which are organic cations implicated in bone growth and development, on differentiation of AT-MSCs. Treatment of goat-derived AT-MSCs with 1,25-dihydroxyvitamin-D3 (1,25(OH)(2)D(3)), which stimulates osteogenic differentiation, for 7 days induced gene expression of the polyamine-modulated transcription factor-1 (PMF-1) and spermidine/spermine N (1)-acetyltransferase (SSAT), which are both involved in polyamine metabolism, suggesting that polyamines are involved in osteogenic differentiation of AT-MSCs. Furthermore, treatment of AT-MSCs with the polyamine spermine-regulated gene expression of runx-2, a transcription factor involved in early stages of osteogenic differentiation, and that of osteopontin, a bone matrix protein expressed in later stages of osteogenic differentiation. Runx-2 gene expression was increased 4 and 14 days after a short 30 min. treatment with spermine, while osteopontin gene expression was only increased 4 days after spermine treatment. Finally, alkaline phosphatase activity, which is intimately involved in the formation of extracellular matrix of bone, was increased 4 weeks after the 30 min.-spermine treatment of AT-MSCs. In conclusion, this study shows for the first time that the polyamine spermine regulates differentiation of AT-MSCs along the osteogenic lineage, which can be used as a new method for differentiation of AT-MSCs along the osteogenic lineage. Therefore, polyamines may constitute a promising tool for bone tissue engineering approaches using AT-MSCs, such as a one-step surgical procedure for spinal interbody fusion.
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PMID:The polymine spermine regulates osteogenic differentiation in adipose stem cells. 1819 60

Since the total flavonoid extract (TFE) of Epimedium herb was found to prevent osteoporosis induced by ovariectomy in rats, we have been attempting to identify the exact compound responsible for the bone-strengthening activity. In this experiment, four flavonoid extracts were obtained from Epimedium sagittatum (Siebold & Zucc.) Maxim, which contained 25.3%, 51.2%, 82.3% and 99.2% icariin respectively. They were separately supplemented into the culture media of newborn rat calvarial osteoblasts (ROB) or primary rat bone marrow stroma cells (rMSCs) at 0.1, 1, 10 and 100 microg/ml respectively, in order to observe their effects on the cells. Not any appreciable effect was found on the differentiation of ROB, but an enhancing effect on the osteogenic differentiation of rMSCs was found, and the enhancing degree was icariin-dependent, that is, a higher concentration of icariin in the extract caused more mineralized bone nodules and higher calcium deposition levels. The gene expressions involved in osteogenesis were also improved which was revealed by RT-PCR, including alkaline phosphatase, bone matrix protein (osteocalcin, osteopontin, bone sialoprotein) and cytokines (TGF-beta1 and IGF-I). The effect of icariin on cell proliferation was assayed by the reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Icariin inhibited the proliferation of rMSCs and ROB when its concentration was higher than 10(-5) microM (6.7 microg/ml), no stimulative effect was found. The above results indicated that icariin may exert bone-strengthening activity by enhancing the osteogenic differentiation of MSCs, which partially explains the anti-osteoporosis action of Epimedium herb.
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PMID:Icariin enhances the osteogenic differentiation of bone marrow stromal cells but has no effects on the differentiation of newborn calvarial osteoblasts of rats. 1823 86

We characterized the temporal changes in chondrogenic genes and developed a staging scheme for in vitro chondrogenic differentiation of human mesenchymal stem cells (hMSCs) in three-dimensional (3D) alginate gels. A time-dependent accumulation of glycosaminoglycans, aggrecan, and type II collagen was observed in chondrogenic but not in basal constructs over 24 days. qRT-PCR demonstrated a largely characteristic temporal pattern of chondrogenic markers and provided a basis for staging the cellular phenotype into four stages. Stage I (days 0-6) was defined by collagen types I and VI, Sox 4, and BMP-2 showing peak expression levels. In stage II (days 6-12), gene expression for cartilage oligomeric matrix protein, HAPLN1, collagen type XI, and Sox 9 reached peak levels, while gene expression of matrilin 3, Ihh, Homeobox 7, chondroadherin, and WNT 11 peaked at stage III (days 12-18). Finally, cells in stage IV (days 18-24) attained peak levels of aggrecan; collagen IX, II, and X; osteocalcin; fibromodulin; PTHrP; and alkaline phosphatase. Gene profiles at stages III and IV were analogous to those in juvenile articular and adult nucleus pulposus chondrocytes. Gene ontology analyses also demonstrated a specific expression pattern of several putative novel marker genes. These data provide comprehensive insights on chondrogenesis of hMSCs in 3D gels. The derivation of this staging scheme may aid in defining maximally responsive time points for mechanobiological modulation of constructs to produce optimally engineered tissues.
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PMID:Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional alginate gels. 1837 98

Two crucial growth factors, FGF2 and TGFbeta1, were investigated in this study to determine their inductive effects on the odontoblastic differentiation of human dental pulp stem cells (DPSCs) in vitro. DPSCs were isolated by immunomagnetic bead selection using the STRO-1 antibody, and then co-cultured respectively with FGF2, TGFbeta1 and FGF2+TGFbeta1. The results showed that FGF2 can exert a significant effect on the cell proliferation, while TGFbeta1 or FGF2+TGFbeta1 can initiate an odontoblast-like differentiation of DPSCs. Moreover, FGF2 can synergistically upregulate the effects of TGFbeta1 on the odontoblastic differentiation of DPSCs, as indicated by the increased alkaline phosphatase activity, the polarized cell appearance and secretary ultrastructural features, the formation of mineralized nodules and the gene/protein expression of dentin sialoprotein and dentin matrix protein-1. Together, FGF2 acted primarily on the cell proliferation, while TGFbeta1 and FGF2+TGFbeta1 mainly stimulated the odontoblastic differentiation of DPSCs. This study provides interesting progress in the odontoblastic differentiation of DPSCs induced by FGF2 and TGFbeta1.
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PMID:Effects of FGF2 and TGFbeta1 on the differentiation of human dental pulp stem cells in vitro. 1844 33


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