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Showing papers on "Alkaline phosphatase published in 2017"


Journal ArticleDOI
TL;DR: The very first reaction-based near-infrared (NIR) probe (DHXP) is developed for sensitive detection of alkaline phosphatase activity both in vitro and in vivo, and possesses excellent biocompatibility and rapid cell-internalization ability.
Abstract: Alkaline phosphatases are a group of enzymes that play important roles in regulating diverse cellular functions and disease pathogenesis. Hence, developing fluorescent probes for in vivo detection of alkaline phosphatase activity is highly desirable for studying the dynamic phosphorylation in living organisms. Here, we developed the very first reaction-based near-infrared (NIR) probe (DHXP) for sensitive detection of alkaline phosphatase activity both in vitro and in vivo. Our studies demonstrated that the probe displayed an up to 66-fold fluorescence increment upon incubation with alkaline phosphatases, and the detection limit of our probe was determined to be 0.07 U/L, which is lower than that of most of alkaline phosphatase probes reported in literature. Furthermore, we demonstrated that the probe can be applied to detecting alkaline phosphatase activity in cells and mice. In addition, our probe possesses excellent biocompatibility and rapid cell-internalization ability. In light of these prominent properties, we envision that DHXP will add useful tools for investigating alkaline phosphatase activity in biomedical research.

117 citations


Journal ArticleDOI
TL;DR: The present switch-on fluorescence sensing strategy for alkaline phosphatase was successfully applied in human serum plasma with good recoveries, revealing that this nanosensor probe is a promising tool for ALP detection.

107 citations


Journal ArticleDOI
TL;DR: The present study revealed that Mg ion and its effective concentration for activating PI3K phosphorylation via TRPM7, which causes three processes affecting bone repair, namely, osteoblast recruitment, osteogenesis and resistance to alkaline stress in human osteoblasts.

100 citations


Journal ArticleDOI
TL;DR: It is demonstrated that ABCC 6 mutant cells are osteogenic and that loss of ABCC6 reduces pyrophosphate, an inhibitor of calcification, and genetic interaction and shared biochemical and cellular mechanisms underlying ectopic calcification in PXE and related disorders caused by defined perturbations in extracellular adenosine 5′-triphosphate catabolism are shared.
Abstract: Biallelic mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a disease characterized by calcification in the skin, eyes, and blood vessels. The function of ATP-binding cassette C6 (ABCC6) and the pathogenesis of PXE remain unclear. We used mouse models and patient fibroblasts to demonstrate genetic interaction and shared biochemical and cellular mechanisms underlying ectopic calcification in PXE and related disorders caused by defined perturbations in extracellular adenosine 5′-triphosphate catabolism. Under osteogenic culture conditions, ABCC6 mutant cells calcified, suggesting a provoked cell-autonomous defect. Using a conditional Abcc6 knockout mouse model, we excluded the prevailing pathogenic hypothesis that singularly invokes failure of hepatic secretion of an endocrine inhibitor of calcification. Instead, deficiency of Abcc6 in both local and distant cells was necessary to achieve the early onset and penetrant ectopic calcification observed upon constitutive gene targeting. ABCC6 mutant cells additionally had increased expression and activity of tissue-nonspecific alkaline phosphatase (TNAP), an enzyme that degrades pyrophosphate, a major inhibitor of calcification. A selective and orally bioavailable TNAP inhibitor prevented calcification in ABCC6 mutant cells in vitro and attenuated both the development and progression of calcification in Abcc6 −/− mice in vivo, without the deleterious effects on bone associated with other proposed treatment strategies.

79 citations


Journal ArticleDOI
TL;DR: The percentile charts provided enable the appropriate differential diagnosis of changes in alkaline phosphatase activity due to disease and changes due to physiological development, and facilitates precise assessment of alkalineosphatase dynamics in pediatrics.
Abstract: Background Interpretation of alkaline phosphatase activity in children is challenging due to extensive changes with growth and puberty leading to distinct sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics and seem reasonable for an analyte as closely linked to growth as alkaline phosphatase. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, resulting in limitations when clinical decisions are based on alkaline phosphatase activity. Methods We applied an indirect method to generate percentile charts for alkaline phosphatase activity using clinical laboratory data collected during the clinical care of patients. A total of 361,405 samples from 124,440 patients from six German tertiary care centers and one German laboratory service provider measured between January 2004 and June 2015 were analyzed. Measurement of alkaline phosphatase activity was performed on Roche Cobas analyzers using the IFCC's photometric method. Results We created percentile charts for alkaline phosphatase activity in girls and boys from birth to 18 years which can be used as reference intervals. Additionally, data tables of age- and sex-specific percentile values allow the incorporation of these results into laboratory information systems. Conclusions The percentile charts provided enable the appropriate differential diagnosis of changes in alkaline phosphatase activity due to disease and changes due to physiological development. After local validation, integration of the provided percentile charts into result reporting facilitates precise assessment of alkaline phosphatase dynamics in pediatrics.

74 citations


Journal ArticleDOI
TL;DR: Investigation of the role of activated charcoal in chronic lead exposure in albino rats confirmed the protective effective of AC against lead induced hepato-renal damage and co-administration of AC significantly decreased biomarkers with the exception of the sperm parameters.
Abstract: Lead is a multi-organ toxicant implicated in various cancers, diseases of the hepatic, renal, and reproductive systems etc. In search of cheap and readily available antidote this study has investigated the role of activated charcoal in chronic lead exposure in albino rats. Eighteen mature male albino rats were used, divided into three groups of six rats per group. Group 1 (control rats) received deionised water (10 ml/kg), group 2 was given lead acetate solution 60 mg/kg and group 3 rats were given lead acetate (60 mg/kg) followed by Activated charcoal, AC (1000 mg/kg) by oral gavage daily for 28 days. Rats in group 2 showed significant increases in serum Aspartate aminotransferase, Alkaline phosphatase, Alanine aminotransferase, urea, bilirubin, total cholesterol, triglycerides, Low Density Lipoprotein, Very Low Density Lipoproteins, Total White Blood Cell Counts, Malondialdehyde, Interleukin-6, and decreases in Packed Cell Volume, hemoglobin concentration, Red blood cell count, total proteins, albumins, superoxide dismutase, glutathione peroxidase and total glutathione. Co-administration of AC significantly decreased these biomarkers with the exception of the sperm parameters. Histopathology of liver and kidney also confirmed the protective effective of AC against lead induced hepato-renal damage. AC may be beneficial in chronic lead induced liver and kidney damage.

67 citations


Journal Article
TL;DR: Data implied that miR-221 played an important part in osteoporosis through regulating RUNX2 expression and osteoblast differentiation through regulating runx2 expression.
Abstract: Introduction MicroRNAs (miRNAs) has emerged as important factors in osteogenesis and chondrogenesis. This study aimed to determine whether miR-221 is involved in the regulation of osteoporosis and its underlying mechanism. Methods Total RNA was extracted from fresh femoral neck trabecular bone from women undergoing hip replacement due to either osteoporotic fracture (OP group, n = 12) or osteoarthritis in the absence of osteoporosis (Control group, n = 12). Gene expression was quantified using TaqMan quantitative RT-PCR assays and protein production was determined by western blot analysis. The role of miR-221 in osteoblast differentiation was identified by gain or loss function experiment. MiRNA targets were identified using bioinformatics and luciferase reporter assay. Results MiR-221 was down-regulated in the osteoporotic samples compared with non-osteoporotic controls, and decreased in a C2C12 cell model of osteogenic differentiation. Overexpression of miR-221 resulted in a decrease in the osteogenic potential, as indicated by the reduced expression levels of key osteoblast markers, including osteocalcin (OC), alkaline phosphatase (ALP) and collagen, type I, α 1 (COL1A1), whereas inhibition of miR-221 promoted the activity of OC, ALP and COL1A1. Then bioinformatic analysis identified potential target sites of the miR-221 located in the 3' untranslated regions of RUNX2. Western blot analysis demonstrated that miR-221 inhibited RUNX2 gene expression. Furthermore, dual-luciferase reporter assays confirmed that RUNX2 was a direct target of miR-221. Rescue experiments showed that overexpression of RUNX2 significantly attenuated the effect of miR-221 on osteoblast markers providing strong evidence that miR-221 mediated the osteoblast differentiation by targeting RUNX2. Conclusions Taken together, these data implied that miR-221 played an important part in osteoporosis through regulating RUNX2 expression and osteoblast differentiation.

66 citations


Journal ArticleDOI
TL;DR: This work reports a convenient and real-time assay of alkaline phosphatase (ALP) in living cells based on a fluorescence quench-recovery process at a physiological pH using the boron-doped graphene quantum dots (BGQDs) as fluorophore.

66 citations


Journal ArticleDOI
19 Jun 2017-PLOS ONE
TL;DR: It is found that primary osteoblasts had higher miR-433-3p level compared with immortal cells through real-time PCR, as well as in situ hybridization experiment, which further emphasized the vital role of miR+3p in DKK1/WNT/β-catenin pathway through decreasing DKK 1 expression and inducing osteoblast differentiation.
Abstract: Dickkopf-1 (DKK1) is a powerful antagonist of canonical WNT signaling pathway, and is regarded as a biomarker for osteoporosis. Its expression is highly correlated with bone mass and osteoblasts maturation. In this study, mouse primary bone marrow cells and osteoblast cell lines were used. Luciferase reporter assay and western blotting methods were employed to validate if miRNA-433-3p epigenetically regulated DKK1 translation. Rat bone marrow derived osteoblasts were infected with lentivirus vector in which miR-433-3p was constructed. The authors constructed lentivirus mediated miRNA-433-3p stable expression and examined the alkaline phosphatase (ALP) activity and mineral deposition level in vitro. In situ hybridization method was used to observe miR-433-3p in primary osteoblasts. We built up an OVX rat model to mimic postmenopausal osteoporosis, and found aberrant circulating miR-433-3p and miR-106b, which were not reported previously. Results showed that miR-433-3p potentially regulated DKK1 mRNA, Furthermore, the correlation of serum DKK1 with circulating miR-433-3p level was significant (r = 0.7520, p = 0.046). In the luciferase reporter assay, we found that miR-433-3p siRNA decreased luminescence signal, indicating direct regulation of miR-433-3p on DKK1 mRNA. When the miR-433-3p binding site in DKK1 3'UTR was mutant, such reduction was prohibited. Western blotting result validated that miR-433-3p inhibited over 90% of DKK1 protein expression. Similarly, the change of protein expression was not observed in mutant group. The stable expression of lentivirus mediated miR-433-3p increased ALP activity and mineralization both in human and rat derived immortalized cells. We found that primary osteoblasts had higher miR-433-3p level compared with immortal cells through real-time PCR, as well as in situ hybridization experiment. Conclusively, our findings further emphasized the vital role of miR-433-3p in DKK1/WNT/β-catenin pathway through decreasing DKK1 expression and inducing osteoblasts differentiation.

57 citations


Journal ArticleDOI
TL;DR: LBPC has a very strong inhibitory effect on S. aureus and can kill it by destroying the integrity and permeability of the cell wall and cell membrane, affecting protein synthesis, and binding to DNA.
Abstract: Larch bark procyanidins (LBPCs) have not only antioxidant and antitumor properties, but also strong bacteriostatic effects. However, it is not clear about the antibacterial mechanisms of LBPC. In this work, the antibacterial effects and mechanisms of LBPC on Staphylococcus aureus were studied in the aspects of morphological structure, cell wall and membrane, essential proteins, and genetic material. The results showed that LBPC effectively inhibited bacterial growth at a minimum inhibitory concentration of 1.75 mg/ml. Bacterial morphology was significantly altered by LBPC treatment, with the cell walls and membranes being destroyed. Extracellular alkaline phosphatase content, bacterial fluid conductivity, and Na+/K+-ATPase and Ca2+-ATPase activities in the membrane system were all increased. In the energy metabolic systems, the activities of succinate dehydrogenase, malate dehydrogenase, and adenosine triphosphatase (ATPase) were all decreased, resulting in a slowdown of metabolism and bacterial growth inhibition. Changes of protein content and composition in the bacteria suggested that the protein expression system was affected. In addition, LBPC was found to bind to DNA grooves to form complexes. Thus, LBPC has a very strong inhibitory effect on S. aureus and can kill S. aureus by destroying the integrity and permeability of the cell wall and cell membrane, affecting protein synthesis, and binding to DNA.

52 citations


Journal ArticleDOI
TL;DR: It could be concluded that sAPS could increase the activities of Astragalus polysaccharides and sodium selenite to protect the liver from damage by attenuating hepatic inflammation, oxidative stress, fibrogenesis, and induces apoptosis and cell cycle arrest in hepatic stellate cells.

Journal ArticleDOI
TL;DR: The effect of the bacterium on growth of Arabidopsis thaliana plant showed that inoculation of bacterial culture exhibited better growth in comparison to the control, and the phosphate solubilizing and alkaline phosphatase production activity of the strain may have probable use for future biotechnological application.

Journal ArticleDOI
TL;DR: A new two-photon fluorescent probe (TP-Phos) is reported to selectively detect ALP activity and offers a number of advantages over previously reported probes, such as fast reaction kinetics, high sensitivity and low cytotoxicity.

Journal ArticleDOI
TL;DR: D-3 has the enormous potential of D-3 as a low-cost and effective anti-iPSC agent for both laboratory use and for the safe clinical application of iPSC-derived cells in regenerative medicine.

Journal Article
TL;DR: Collagen scaffold with immobilized alkaline phosphatase can be utilized as a good candidate for enhancing the differentiation of osteoblasts from mesenchymal stem cells.
Abstract: Background In tissue engineering, scaffold characteristics play an important role in the biological interactions between cells and the scaffold. Cell adhesion, proliferation, and activation depend on material properties used for the fabrication of scaffolds. Objective In the present investigation, we used collagen with proper characteristics including mechanically stability, biodegradability and low antigenicity. Optimization of the scaffold was done by immobilization of alkaline phosphatase on the collagen surface via cross-linking method, because this enzyme is one of the most important markers of osteoblast, which increases inorganic phosphate concentration and promote mineralization of bone formation. Methods Alkaline phosphatase was immobilized on a collagen surface by 1-ethyl-3-(dimethylaminopropyl) carbodiimide hydrochloride, as a reagent. Then, rat mesenchymal stem cells were cultured in osteogenic medium in control and treated groups. The osteogenesis-related genes were compared between treatments (differentiated cells with immobilized alkaline phosphatase/collagen scaffold) and control groups (differentiated cells on collagen surface without alkaline phosphatase) on days 3 and 7 by quantitative real-time PCR (QIAGEN software). Results Several genes, including alkaline phosphatase, collagen type I and osteocalcine associated with calcium binding and mineralization, showed upregulation in expression during the first 3 days, whereas tumor necrosis factor-α, acting as an inhibitor of differentiation, was down-regulated during osteogenesis. Conclusion Collagen scaffold with immobilized alkaline phosphatase can be utilized as a good candidate for enhancing the differentiation of osteoblasts from mesenchymal stem cells.

Journal ArticleDOI
TL;DR: It was found thatrhBMP9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rhBMP2 by demonstrating higher levels of ALP expression and alizarin red staining, and ALP staining up to 25-fold, when compared with rhB MP2.
Abstract: OBJECTIVES: Combination therapies of growth factors and scaffolds for bone tissue engineering are becoming routine for clinical use. BMP9 has previously been characterized as one of the most osteogenic inducers among the BMP superfamily; however, up until recently, BMP9 has only been available through adenovirus transfection experiments (gene therapy). While recombinant human (rh)BMP2 is regarded as the gold standard for bone regeneration with recombinant growth factors, recently the successful development of rhBMP9 brings intriguing new possibilities for future clinical use. The purpose of this pioneering study was to investigate the effects of rhBMP9 in comparison with rhBMP2 on an in vitro cell behavior of bone-forming osteoblasts when combined with a bone grafting material. MATERIAL AND METHODS: Undifferentiated mouse ST2 stromal bone marrow cells were seeded onto bovine-derived natural bone mineral (NBM) particles treated with (i) control, (ii) rhBMP2 (10 ng/ml), (iii) rhBMP2 (100 ng/ml), (iv) rhBMP9 (10 ng/ml) and (v) rhBMP9 (100 ng/ml). The effects of rhBMPs were compared for cell adhesion at 8 h, cell proliferation at 1, 3 and 5 days and osteoblast differentiation as assessed by real-time PCR at 3 and 14 days for genes encoding Runx2, collagen1alpha2 (COL1a2), alkaline phosphatase (ALP) and osteocalcin (OCN). Furthermore, ALP staining and alizarin red staining were used to investigate localization of osteoblast differentiation marker and mineralization on NBM. RESULTS: Although neither rhBMP2 nor rhBMP9 influenced cell attachment to NBM particles, both were able to stimulate cell proliferation at 3 days. Furthermore, all concentrations of rhBMPs were able to significantly induce mRNA levels of Runx2, COL1a2 and OCN at 3 days. Interestingly, only rhBMP9 was able to significantly upregulate mRNA levels of ALP up to eightfold, and ALP staining up to 25-fold, when compared to rhBMP2. In addition, only rhBMP9 (100 ng/ml) significantly increased alizarin red staining when compared to control and rhBMP2 (10 ng/ml) samples. CONCLUSION: These results demonstrate that both rhBMP2 and rhBMP9 have osteopromotive properties on osteoblast differentiation. It was found that rhBMP9 additionally stimulated the osteopromotive potential of osteoblasts when compared to rhBMP2 by demonstrating higher levels of ALP expression and alizarin red staining. Further animal studies comparing both recombinant proteins are necessary to further characterize the osteoinductive potential of BMP9.

Journal ArticleDOI
TL;DR: Primary osteoblasts constitutively express IL- 17 receptors, but none of C2C12 cells, MC3T3-E1 cells, and Saos-2 cells express any receptors for IL-17, IL-22, and IL-23.
Abstract: Objectives. To examine the expressions of IL-17, IL-22, and IL-23 receptors in four osteoblast models and the effects of IL-17, IL-22, and IL-23 on osteoblasts. Methods. Gene expression levels of receptors, alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (Runx-2), were evaluated by RT-PCR and real-time RT-PCR. Proliferative responses and cell cycle analysis were detected by a CCK-8 assay and flow cytometry, respectively. ALP activity and ALP mass were detected by an ALP activity assay and ALP staining, respectively. Results. In primary osteoblasts, only the IL-17 receptor was expressed. In C2C12, MC3T3-E1, and Saos-2 cells, the genes of IL-17, IL-22, and IL-23 receptors were not detectable. None of IL-17, IL-22, and IL-23 had an obvious effect on the proliferation of primary osteoblasts, but IL-17 exhibited an inhibitory effect on the gene expression of ALP, OCN, and Runx-2. The ALP activity and ALP mass of primary osteoblasts were downregulated by IL-17 treatment in a dose-dependent manner, and IL-17 failed to inhibit BMP-2-induced phosphorylation of Smad. Conclusion. Primary osteoblasts constitutively express IL-17 receptors, but none of C2C12 cells, MC3T3-E1 cells, and Saos-2 cells express any receptors for IL-17, IL-22, and IL-23. IL-17 inhibits BMP-2-induced osteoblast differentiation via the BMP/Smad-independent pathway.

Journal ArticleDOI
TL;DR: In this article, the effect of biomechanical stimulation on osteoblast differentiation of human periosteal-derived stem cells using the newly developed bioreactor was investigated. But, the results were limited to the extraction of an impacted third molar.
Abstract: This study was to investigate the effect of biomechanical stimulation on osteoblast differentiation of human periosteal-derived stem cell using the newly developed bioreactor. Human periosteal-derived stem cells were harvested from the mandible during the extraction of an impacted third molar. Using the new bioreactor, 4% cyclic equibiaxial tension force (0.5 Hz) was applied for 2 and 8 h on the stem cells and cultured for 3, 7, and 14 days on the osteogenic medium. Biochemical changes of the osteoblasts after the biomechanical stimulation were investigated. No treatment group was referred to as control group. Alkaline phosphatase (ALP) activity and ALP messenger RNA (mRNA) expression level were higher in the strain group than those in the control group. The osteocalcin and osteonectin mRNA expressions were higher in the strain group compared to those in the control group on days 7 and 14. The vascular endothelial growth factor (VEGF) mRNA expression was higher in the strain group in comparison to that in the control group. Concentration of alizarin red S corresponding to calcium content was higher in the strain group than in the control group. The study suggests that cyclic tension force could influence the osteoblast differentiation of periosteal-derived stem cells under optimal stimulation condition and the force could be applicable for tissue engineering.

Journal ArticleDOI
TL;DR: It is indicated that metformin can enhance osteogenic differentiation of CV-MSCs and reduce adipocyte formation, and may be associated with eNOS expression.
Abstract: Metformin is the first-line anti-hyperglycemic drugs commonly used to treat type 2 diabetes. Recent studies have shown that metformin can enhance bone formation through induction of endothelial nitric oxide synthase (eNOS). Human chorionic villous mesenchymal stem cells (CV-MSCs) are promising candidates for regenerative medicine. The present study aimed to investigate the effects of metformin on the osteogenic and adipocytic differentiation of human CV-MSCs, and to elucidate the underlying mechanism. CV-MSCs, prepared from human term placentae, were cultured with different concentrations of metformin. Treatment for 72 hours with 0.05 mM metformin had no noticeable effect on the proliferation of CV-MSCs. Consequently, CV-MSCs were cultured for seven or 14 days in the osteogenic medium supplemented with 0.05 mM metformin. Treatment for seven days with metformin increased the expression levels of osteogenic protein mRNAs, including alkaline phosphatase, runt-related transcription factor 2, and osteopontin. Metformin also enhanced the mineralization of CV-MSCs. Furthermore, metformin induced the expression of eNOS in CV-MSCs during osteogenic differentiation. By contrast, when CV-MSCs were cultured for 14 days in the adipogenic medium, 0.05 mM metformin inhibited the expression of adipogenic protein mRNAs, including proliferators-activated receptor-γ and CCAAT/enhancer binding protein-α. The lipid droplet accumulation was also reduced on 28 days after metformin treatment. These findings indicate that metformin can enhance osteogenic differentiation of CV-MSCs and reduce adipocyte formation. The effect of metformin on osteogenic differentiation of CV-MSCs may be associated with eNOS expression. Our findings will highlight the therapeutic potential of metformin in osteoporosis and bone fracture.

Journal ArticleDOI
TL;DR: A compression bioreactor system that applies cyclic compression to cellular grafts in a controlled manner suggested that cyclic, physiological compression of stem cell-seeded scaffolds generated highly mineralized bone grafts.
Abstract: Application of dynamic mechanical loads on bone and bone explants has been reported to enhance osteogenesis and mineralization. To date, published studies have incorporated a range of cyclic strains on 3D scaffolds and platforms to demonstrate the effect of mechanical loading on osteogenesis. However, most of the loading parameters used in these studies do not emulate the in vivo loading conditions. In addition, the scaffolds/platforms are not representative of the native osteoinductive environment of bone tissue and hence may not be entirely accurate to study the in vivo mechanical loading. We hypothesized that biomimicry of physiological loading will potentiate accelerated osteogenesis in bone grafts. In this study, we present a compression bioreactor system that applies cyclic compression to cellular grafts in a controlled manner. Polycaprolactone-β Tricalcium Phosphate (PCL-TCP) scaffolds seeded with Mesenchymal Stem Cells (MSC) were cyclically compressed in bioreactor for a period of 4 weeks at 1 Hz and physiological strain value of 0.22% for 4 h per day. Gene expression studies revealed increased expressions of osteogenesis-related genes (Osteonectin and COL1A1) on day 7 of cyclic loading group relative to its static controls. Cyclic compression resulted in a 3.76-fold increase in the activity of Alkaline Phosphatase (ALP) on day 14 when compared to its static group (p < 0.001). In addition, calcium deposition of cyclic loading group was found to attain saturation on day 14 (1.96 fold higher than its static scaffolds). The results suggested that cyclic, physiological compression of stem cell-seeded scaffolds generated highly mineralized bone grafts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2366-2375, 2017.

Journal ArticleDOI
TL;DR: In vivo, the "Sr-a-polyP-MP" packed into PLGA microspheres and implanted into critical-size calvarial defects in rats resulted in a speeded up of the healing/mineralization of the bone defect.

Journal ArticleDOI
TL;DR: There is emerging evidence that FGF23 is a pleiotropic hormone, linking bone with several other organ systems, and may have important implications for the pathophysiology of chronic kidney disease.
Abstract: Fibroblast growth factor-23 (FGF23) is a bone-derived hormone, mainly produced by osteoblasts and osteocytes in response to increased extracellular phosphate and circulating vitamin D hormone. Endocrine FGF23 signaling requires co-expression of the ubiquitously expressed FGF receptor 1 (FGFR1) and the co-receptor α-Klotho (Klotho). In proximal renal tubules, FGF23 suppresses the membrane expression of the sodium-phosphate cotransporters Npt2a and Npt2c which mediate urinary reabsorption of filtered phosphate. In addition, FGF23 suppresses proximal tubular expression of 1α-hydroxylase, the key enzyme responsible for vitamin D hormone production. In distal renal tubules, FGF23 signaling activates with-no-lysine kinase 4, leading to increased renal tubular reabsorption of calcium and sodium. Therefore, FGF23 is not only a phosphaturic but also a calcium- and sodium-conserving hormone, a finding that may have important implications for the pathophysiology of chronic kidney disease. Besides these endocrine, Klotho-dependent functions of FGF23, FGF23 is also an auto-/paracrine suppressor of tissue-nonspecific alkaline phosphatase transcription via Klotho-independent FGFR3 signaling, leading to local inhibition of mineralization through accumulation of pyrophosphate. In addition, FGF23 may target the heart via an FGFR4-mediated Klotho-independent signaling cascade. Taken together, there is emerging evidence that FGF23 is a pleiotropic hormone, linking bone with several other organ systems.

Journal ArticleDOI
TL;DR: This study investigates proliferative and osteogenic differentiation potentials of gingival mesenchymal stem/progenitor cells (G-MSCs), influenced by IL-1/TNF-α inflammatory/anti-inflammatory conditions and concludes that selective anti-inflammatory intervention could boost G- MSCs' differentiation.
Abstract: Cytokines play major roles in tissue destruction/repair. The present study investigates proliferative and osteogenic differentiation potentials of gingival mesenchymal stem/progenitor cells (G-MSCs), influenced by IL-1/TNF-α inflammatory/anti-inflammatory conditions. Human G-MSCs were isolated, characterized, and cultured in basic medium (control group, M1), in basic medium with IL-1β, TNF-α, and IFN-γ (inflammatory group, M2) and with IL-1ra/TNF-αi added to M2 (anti-inflammatory group, M3). MTT tests at days 1, 3, and 7 and CFU assay at day 12 were conducted. Osteogenic differentiation was analyzed by bone-specific transcription factors (RUNX2), alkaline phosphatase (ALP), type I collagen (Col-I), osteopontin (OPN), and osteonectin (ON) expression at days 1, 3, 7, and 14 and Alizarin red staining at day 14. At day 3, the control group showed the highest cell numbers. At day 7, cell numbers in inflammatory and anti-inflammatory group outnumbered the control group. At day 12, CFUs decreased in the inflammatory and anti-inflammatory groups, with altered cellular morphology. The anti-inflammatory group demonstrated elevated bone-specific transcription factors at 14 days. After 14 days of osteogenic induction, calcified nodules in the anti-inflammatory group were higher compared to control and inflammatory groups. For regeneration, initial inflammatory stimuli appear essential for G-MSCs' proliferation. With inflammatory persistence, this positive effect perishes and is followed by a short-term stimulatory one on osteogenesis. At this stage, selective anti-inflammatory intervention could boost G-MSCs' differentiation.

Journal ArticleDOI
TL;DR: The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH2, -COOH and S=O) inHIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.
Abstract: The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH2, -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.

Journal ArticleDOI
TL;DR: The results show that Fe concentration had significant effect on physical and mechanical properties of TCP ceramics, and also on the in vitro osteoblast cellular interactions in TCP ceramic.
Abstract: Iron (Fe) is a vital element and its deficiency causes abnormal bone metabolism. We investigated the effects of Fe and its concentration in β-tricalcium phosphate (β-TCP) on physicomechanical properties and in vitro proliferation and differentiation of osteoblasts. Our results showed that Fe addition at concentrations of 0.5 wt.% (0.5 Fe-TCP) and 1.0 wt.% (1.0 Fe-TCP) inhibits the β-TCP to α-TCP phase transformation at sintering temperature of 1250 °C. Addition of 0.25 wt.% Fe (0.25 Fe-TCP) increased the compressive strength of β-TCP from 167.27 ± 16.2 to 227.10 ± 19.3 MPa. After 3 days of culture, surfaces of 0.5 Fe-TCP and 1.0 Fe-TCP samples were covered by osteoblast cells, compared to that of pure and 0.25 Fe-TCP. Cells grew to confluency on all Fe-doped samples after 7 days of culture and monolayer sheet-like cellular structure was found at 11 days. Optical cell density and alkaline phosphatase activity were significantly higher on Fe-doped samples and the highest values were found in 0.5 Fe-TCP samples. Our results show that Fe concentration had significant effect on physical and mechanical properties of TCP ceramics, and also on the in vitro osteoblast cellular interactions in TCP ceramics.

01 Jan 2017
TL;DR: Starvation did not alter the jejunal histological findings in three subjects in whom small bowel biopsies were done, but activities of alkaline phosphatase, sucrase, and maltase in the small bowel mucosa decreased.
Abstract: stances measured was identical in normal\x=req-\ weight and obese groups. After the five-day fast, the absorption of glucose, water, sodium, chloride, and folic acid and the secretion of urea declined significantly. Starvation did not alter the jejunal histological findings in three subjects in whom small bowel biopsies were done, but activities of alkaline phosphatase, sucrase, and maltase in the small bowel mucosa decreased.

01 Jan 2017
TL;DR: Confusion may still exist when there is elevated SGO-T activity in the absence of electrocardiographic evidence of heart muscle damage, especially when the electrocardsiogram reveals equivocal changes, previous infarction, left bundle branch block, or arrhythmia.
Abstract: An increase of serum glutamic oxalacetic transaminase (SGO-T) activity following myocardial infarction was first described by LaDue et al. 1 and subsequently confirmed by numerous investigators. 2-6 Much emphasis has been placed on elevated SGO-T values in substantiating the clinical impression of myocardial infarction, especially when the electrocardiogram reveals equivocal changes, previous infarction, left bundle branch block, or arrhythmia. 7-9 With increased understanding of the ubiquitous nature of GO-T distribution in human tissues, it has become apparent that liver necrosis 10-14 and a host of other disease states 5,6,15-21 can provoke a rise in SGO-T activity. Thus, confusion may still exist when there is elevated SGO-T activity in the absence of electrocardiographic evidence of heart muscle damage. Obstructive biliary tract disease causes a rise in SGO-T activity, 22,23 and this rise may be unrelated to hepatic necrosis. 24 The demonstration of high GO-T activity in bile 25 further serves to

Journal ArticleDOI
TL;DR: The results show that the extract of H. letestui has hepatoprotective potential which may be due to the antioxidant activity of its phytoconstituents.
Abstract: Homalium letestui Pellegr (Flacourtiaceae) is used traditionally by the Ibibios of Southern Nigeria to treat stomach ulcer, malaria and other inflammatory diseases and Yorubas of western Nigeria as an antidote. The hepatoprotective effect of the stem extract (200-600 mg/kg) was evaluated by the assay of liver function parameters, namely total and direct bilirubin, serum protein and albumin, total cholesterol, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and alkaline phosphatase activities (ALP), antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and histopathological study of the liver. GCMS analysis of n-butanol fraction was carried out. Administration of the stem extract caused a significant (p

Journal ArticleDOI
TL;DR: In cultures of osteoblast-lineage cells, lactate promoted alkaline phosphatase-positive cell formation, increased the activity of alkalineosphatase, and induced the expression of osteocalcin, revealing an unrecognized role for aerobic glycolysis in osteOBlast differentiation via its end product, lactates.

Journal ArticleDOI
TL;DR: BPA increase gamma globulin protein levels and decreases the level of alkaline phosphatase, aspartate aminotransferase and serum protein β2 and causes weight loss in rats after treatment, and it is demonstrated that the toxic effect of BPA on liver is induced by oxidative stress.