Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidences suggest that the activation of peroxisome proliferator-activated receptor (PPAR)-gamma, which is an important transcriptional factor in adipocyte differentiation, also plays an important role in the bone microenvironment. The objective of the study was to clarify whether Pro12Ala polymorphism was related to the serum OPG levels and bone mineral metabolism in healthy Korean women. In 239 Korean women (mean age 51 years), who participated in medical check-up program in a health promotion center, anthropometric measurements, lumbar spine and femoral neck bone mineral density (BMD), bone turnover markers, such as serum total alkaline phosphatase (ALP) levels, urine deoxypyridinoline levels, and 24-h urine calcium excretion were measured. Serum levels of OPG were measured with ELISA method. DNAs were extracted from the samples and the genotyping of the Pro12Ala polymorphism (rs1801282) in the PPAR-gamma gene was performed via an allelic discrimination assay using a TaqMan probe. In addition, we examined the haplotype analysis between two polymorphisms of PPAR-gamma gene, Pro12Ala in exon B and C161T in exon 6 (rs3856806). Allelic frequencies were 0.950 for Pro allele and 0.050 for Ala allele, which was in compliance with Hardy- Weinberg equilibrium, and there was no Ala12Ala genotype among the genotyped subjects. Mean serum OPG level was significantly lower (P=0.035), and serum total ALP was significantly higher (P=0.014) in the Pro12Ala genotype group compared with the Pro12Pro genotype group, which were consistently significant even after adjustment for weight, height, and serum follicle stimulating hormone (FSH). In multiple regression analysis with serum OPG as the dependent variable and age, weight, ALP, femoral neck BMD and Pro12Ala genotype included in the model, only Pro12Ala genotype was significant determinant of serum OPG level (b=??0.136, P=0.035). The haplotype analysis with C161T polymorphism revealed that subjects with Ala and T alleles showed significantly lower serum OPG levels compared with those with Pro12Pro/CC genotype, which were consistently significant even after adjustment for age, weight, height and FSH (P=0.010). This result suggests statistically significant association of Pro12Ala polymorphisms with serum OPG levels in Korean females.
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PMID:The association of Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma gene with serum osteoprotegerin levels in healthy Korean women. 1816 Aug 40

To elucidate the mechanism of the effect of bisphosphonates on bone metabolism, we investigated the effect of alendronate, a widely used bisphosphonate, on osteogenic and adipogenic differentiation in bone marrow stromal cells (BMSCs) derived from ovariectomized SD rats. Alendronate treatment not only increased the mRNA level of bone morphogenetic protein-2, runt-related transcription factor 2, osteopontin, bone sialoprotein, and alkaline phosphatase activity after osteogenic induction, but also decreased the mRNA level of peroxisome proliferator activated receptor gamma 2 and total droplet number indicated by Oil Red O staining after adipogenic induction. The effect of alendronate treatment was dose-dependent, and the difference of the osteogenic or the adipogenic potential between the treated group and the non-treated group was statistically significant (p<0.001). The MAPK-specific inhibitors, PD98059 and SP600125, but not the p38-specific inhibitor, blocked the alendronate-induced regulation of BMSC differentiation. Analysis of BMSCs induced in the presence of alendronate revealed an immediate increase in ERK and JNK phosphorylation. Taken together, these data suggest that alendronate acts on BMSCs to stimulate osteogenic differentiation and inhibit adipogenic differentiation in a dose-dependent manner; this effect is mediated via activating ERK and JNK.
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PMID:Stimulation of osteogenic differentiation and inhibition of adipogenic differentiation in bone marrow stromal cells by alendronate via ERK and JNK activation. 1848 85

Dihydroxy-cholecalciferol [1,25(OH)2D3] has been shown to have pleiotropic effects on the differentiation of mesenchymal stem cells (MSC) based on species and culture conditions. We have examined the effects of 1,25(OH)2D3 on the differentiation of porcine MSC under culture conditions designed to promote proliferation in order to attempt to mimic the conditions in young, rapidly growing animals. The MSC were isolated from bone marrow of a young pig and grown in basal media (BM) containing DMEM+10% fetal bovine serum and antibiotics. Cells received either BM, BM+10(-8) M 1,25(OH)2D3 or BM+10(-7) M 1,25(OH)2D3 with complete media changes every 3 days for a total of 12 days of culture. On days 3, 6, 9 and 12, viable cell numbers were determined, and samples were collected for gene expression analysis and cytochemical staining. There was a treatment-based reduction in cell numbers on 6, 9 and 12 days (P<.05). The concentrations of mRNAs encoding peroxisome proliferator-activated receptor gamma, lipoprotein lipase, and adipocyte-binding protein 2 were increased (P<.05) in a manner indicative of adipocytic differentiation by treatment with 1,25(OH)2D3 in a dose-dependent manner. However, the mRNA levels of osteocalcin, a late stage marker of osteoblastic differentiation, was also increased (P<.05) by treatment with 1,25(OH)2D3. An increased percentage of lipid filling, based on Oil Red O staining, and decreased alkaline phosphatase activity, was also seen with 1,25(OH)2D3 treatment. These data suggest that 1,25(OH)(2)D(3) stimulates the differentiation of porcine MSC towards an adipocytic phenotype.
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PMID:Dihydroxy-cholecalciferol stimulates adipocytic differentiation of porcine mesenchymal stem cells. 1878 67

Conjugated linoleic acid (CLA) describes a group of isomers of linoleic acid and has variable effects on bone formation and adiposity in vivo and in vitro. The variability may be due to individual effects of the predominant bioactive 9cis,11trans (9,11) and 10trans,12cis (10,12) CLA isomers. Osteoblasts and adipocytes are derived from mesenchymal stem cells (MSCs), and bone loss is accompanied by an increase in marrow adiposity. Osteoblast differentiation from MSCs requires activation of Wnt/beta-catenin signaling by Wnt10b, which inhibits adipocyte differentiation by suppressing CCAAT/enhancer-binding protein (C/EBP) alpha. The objective of this study was to determine if 9,11 and 10,12 CLA affect osteoblast and adipocyte differentiation from MSCs and to determine whether any effects are associated with changes in Wnt10b and C/EBPalpha expression. Osteoblast differentiation was assessed by calcium deposition, alkaline phosphatase (ALP) activity, and the expression of Wnt10b, runx2 and osteocalcin. Adipocyte differentiation was assessed by oil red O staining and C/EBPalpha, PPARgamma and FABP4 expression. Compared to vehicle, 9,11 CLA decreased calcium deposition ( approximately 15%), increased oil red O staining ( approximately 21-28%) and increased FABP4 (AP2) expression ( approximately 58-75%). In contrast, 10,12 CLA increased calcium deposition ( approximately 12-60%), ALP activity ( approximately 2.1-fold) and the expression of Wnt10b ( approximately 60-80%) and osteocalcin ( approximately 90%), but decreased oil red O staining ( approximately 30%) and the expression of C/EBPalpha ( approximately 24-38%) and PPARgamma ( approximately 60%) (P<.05). Thus, our findings demonstrate isomer-specific effects of CLA on MSC differentiation, and suggest that 10,12 CLA may be a useful therapeutic agent to promote osteoblast differentiation from MSCs.
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PMID:Regulation of osteoblast and adipocyte differentiation from human mesenchymal stem cells by conjugated linoleic acid. 1901 68

Lactoferrin accelerates bone formation, but the precise cellular mechanism behind this is still unclear. We examined the effect of lactoferrin on the differentiation of pluripotent mesenchymal cells using a typical pluripotent mesenchymal cell line, C2C12. Cells were cultured in low-mitogen differentiation medium to induce cell differentiation, with or without the addition of lactoferrin. The cell lineage was determined by alkaline phosphatase (ALPase) activity, mRNA expression of cellular phenotype-specific markers using real-time polymerase chain reaction (PCR), and protein synthesis using Western blotting. The expression of low-density lipoprotein lipase receptor-related proteins (LRPs) 1 and 2, both lactoferrin receptors, was determined by reverse transcription-PCR. ALPase activity increased after the addition of lactoferrin. The mRNA expression of Runx2, osteocalcin, and Sox9 increased markedly as a result of lactoferrin treatment, whereas the expression of MyoD, desmin, and PPARgamma decreased significantly. Western blots showed that lactoferrin stimulation increased Runx2 and Sox9 proteins, whereas it decreased MyoD and PPARgamma synthesis. C2C12 cells expressed the LRP1 lactoferrin receptor. These results indicate that lactoferrin treatment converts the differentiation pathway of C2C12 cells into the osteoblastic and chondroblastic lineage.
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PMID:Effects of lactoferrin on the differentiation of pluripotent mesenchymal cells. 1910 98

TBR31-2 is one of the bone marrow stromal cell lines. Differentiation toward osteogenic cells and calcification was observed when TBR31-2 cells were cultured for 4 weeks. Bone morphogenetic protein-2 (BMP-2) stimulated alkaline phosphatase (ALP) activity in a dose- and time-dependent manner. On the other hand, troglitazone increased oil droplet accumulation in a dose-dependent manner. In the presence of BMP-2, an increase of expression in osteogenic cell differentiation marker genes and a decrease of expression in adipocyte differentiation marker genes were observed with the exception of the induced expression of peroxisome proliferator-activated receptor gamma (PPARgamma), however, troglitazone, a ligand of PPARgamma treatment exhibited the opposite tendency. Interestingly, treatment with both BMP-2 and troglitazone resulted in a decrease of ALP activity and an increase of oil droplet accumulation. Reverse tanscription-polymerase chain reaction (RT-PCR) analysis also indicated that osteogenic differentiation markers decreased and that adipocyte differentiation markers increased. Thus, when the cells were cultured with BMP-2, osteogenic differentiation was enhanced while the expression of PPARgamma was maintained, and the addition of troglitazone caused a significant number of differentiated cells into adipocytes. These findings indicate that BMP-2 enhanced osteogenic differentiation and the expression of adipogenic transcription factor (PPARgamma) followed by osteogenic differentiation without activation of PPARgamma by its ligand.
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PMID:Effect of bone morphogenetic protein-2 (BMP-2) or troglitazone, as an inducer of osteogenic cells or adipocytes, on differentiation of a bone marrow mesenchymal progenitor cell line established from temperature-sensitive (ts) simian virus (SV) 40 T-antigen gene transgenic mice. 1912 73

Ghrelin is a 28-residue peptide identified in the stomach as an endogenous ligand of the growth hormone secretagogue receptor that is expressed in a variety of peripheral tissues, as well as in the brain. In previous studies, ghrelin has been shown to stimulate both adipogenic differentiation from preadipocytes and osteogenic differentiation from preosteoblasts or primary osteoblasts. This study was undertaken to investigate the direct effect of ghrelin on the lineage allocation of mesenchymal stem cells (MSCs). We identified ghrelin receptor mRNA in C3H10T1/2 cells, and we found the levels of this mRNA to be attenuated during osteogenic differentiation. Treatment of cells with ghrelin resulted in both proliferation and inhibition of caspase-3 activity. In addition, ghrelin decreased serum deprivation-induced bax protein expression and release of cytochrome c from the mitochondria, whereas it increased bcl-2 protein expression. Moreover, ghrelin inhibited early osteogenic differentiation, as shown by alkaline phosphatase activity and staining, and inhibited osteoblast-specific genes expression by altering Runx2, PPARgamma, and C/EBPalpha protein expression.
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PMID:Ghrelin inhibits early osteogenic differentiation of C3H10T1/2 cells by suppressing Runx2 expression and enhancing PPARgamma and C/EBPalpha expression. 1916 Apr 22

Growth plate cartilage is responsible for long bone growth in children and adolescents and is regulated by vitamin D metabolites in a cell zone-specific manner. Resting zone chondrocytes (RC cells) are regulated by 24,25-dihydroxyvitamin D3 via a phospholipase D-dependent pathway, suggesting downstream phospholipid metabolites are involved. In this study, we showed that 24R,25(OH)2D3 stimulates rat costochondral RC chondrocytes to release lysophosphatidic acid (LPA) and, therefore sought to determine the role of LPA signaling in these cells. RC cells expressed the G-protein coupled receptors LPA1-5 and peroxisome proliferator-activated receptor gamma (PPAR-gamma). LPA and the LPA1/3 selective agonist OMPT increased proliferation and two maturation markers, alkaline phosphatase activity and [35S]-sulfate incorporation. LPA and 24R,25(OH)2D3's effects were inhibited by the LPA1/3 selective antagonist VPC32183(S). Furthermore, apoptosis induced by either inorganic phosphate or chelerythrine was attenuated by LPA, based on DNA fragmentation, TUNEL staining, caspase-3 activity, and Bcl-2:Bax protein ratio. LPA prevented apoptotic signaling by decreasing the abundance, nuclear localization, and transcriptional activity of the tumor-suppressor p53. LPA treatment also regulated the expression of the p53-target genes Bcl-2 and Bax to enhance cell survival. Collectively, these data suggest that LPA promotes differentiation and survival in RC chondrocytes, demonstrating a novel physiological function of LPA-signaling.
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PMID:Lysophosphatidic acid signaling promotes proliferation, differentiation, and cell survival in rat growth plate chondrocytes. 1923 32

Human adipose-derived stem cells (hASCs) offer great promise for bone tissue engineering because of their osteogenic differentiation potential. At molecular levels, this study investigated the contribution of one of the main members of mitogen-activated protein kinases (MAPKs), extracellular signal-related kinase (ERK), to hASC osteogenic differentiation and the regulation of ERK for the balance between osteogenesis and adipogenesis in hASCs in vitro. As analyzed using western blot, ERK activation in osteo-induced hASCs was initiated at day 7, peaked at day 10, and declined from day 14 to basal levels. As detected using histochemical and biochemical methods, alkaline phosphatase (ALP) activity in hASCs experienced a process similar to that of ERK activation. Inhibition of ERK activation by PD98059, a specific inhibitor of the ERK signaling pathway, blocked the osteogenic differentiation in a dose-dependent manner, as revealed by an ALP activity assay, extracellular calcium deposition detection, osteocalcin (OCN) secretion examination, and real-time polymerase chain reaction (PCR) analysis for expression of osteogenesis-relative genes: core binding factor alpha 1, collagen type I, ALP, and OCN. Blockage of ERK phosphorylation in osteo-induced hASCs by PD98059 supplemented with dexamethasone (Dex) led to adipogenic differentiation, as confirmed by Nile Red staining to detect intracellular lipid droplets and real-time PCR analysis for expression of adipogenesis-relative genes: peroxisome proliferator-activated receptor gamma 2 and fatty acid-binding protein. These findings indicated a potential mechanism for the function of ERK in hASC osteogenic differentiation, especially the regulation of ERK in association with Dex for the balance between osteogenesis and adipogenesis, pointing out the significance of ERK signaling pathway for ASCs as a promising cell source for bone tissue engineering.
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PMID:The role of the extracellular signal-related kinase signaling pathway in osteogenic differentiation of human adipose-derived stem cells and in adipogenic transition initiated by dexamethasone. 1943 23

To evaluate the effects of dietary hemicellulose from corn on growth and metabolic measures, female pigs (n = 48; initial BW 30.8 kg) were fed diets containing 0 to 38.6% solvent-extracted corn germ meal for 28 d. Increasing the hemicellulose level had no impact on ADG or ADFI, but resulted in a quadratic response (P < 0.03) on G:F. To investigate physiological changes that occur with increased dietary hemicellulose, blood, colon contents, and tissue samples from the liver and intestine were obtained from a subset (n = 16; 8 pigs/treatment) of pigs fed the least and greatest hemicellulose levels. The abundance of phospho-adenosine monophosphate-activated protein kinase (AMPK) and the mitochondrial respiratory protein, cytochrome C oxidase II (COXII) were determined in liver, jejunum, ileum, and colon by Western blotting. The mRNA expression levels of AMPKalpha1, AMPKalpha2, PPAR coactivator 1alpha (PGC1-alpha), PPARgamma2, and sirtuin 1 (Sirt1) were determined in liver and intestinal tissues. When compared with pigs fed the control diet, pigs fed the high hemicellulose diet had increased (P < 0.02) plasma triglycerides, but there was no difference in plasma cholesterol, glucose, or insulin. Absolute and relative liver weights were decreased (P < 0.03) in pigs consuming the high hemicellulose diet. The high-fiber diet led to a tendency (P < 0.12) for decreased liver triglyceride content. In pigs fed the high hemicellulose diet, ileal mucosal alkaline phosphatase activity was increased (P < 0.08) and sucrase activity tended (P < 0.12) to be increased. The high hemicellulose diet had no effect on phospho-AMPK, AMPK mRNA, or colonic VFA, but in pigs consuming the high fiber diet there was a greater (P < 0.05) abundance of COXII in colon tissue. The expression of PGC1-alpha, PPARgamma, or Sirt1 mRNA was not altered by dietary fiber in liver, jejunum, or ileum tissue. In colon tissue from pigs fed the high fiber diet there was an increase (P < 0.09) in Sirt1 mRNA and a trend (P < 0.12) toward increased of PGC1-alpha mRNA. These data suggest that alterations in metabolism involved in adaptation to a diet high in hemicellulose are associated with increased colonic Sirt1 mRNA and COXII expression, indicating an increased propensity for oxidative metabolism by the intestine.
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PMID:Evaluation of elevated dietary corn fiber from corn germ meal in growing female pigs. 1978 91


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