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)

Three types of bone metastasis can be identified : the osteolytic, osteoblastic and the intertrabecular metastasis. Bone resorption is believed to be responsible for osteolytic metastasis. The early stage of metastatic lesion showed tumor cells loosely intermingled with osteoblasts, fibroblastic stromal cells, osteoclasts and endothelial cells. In the metastatic nest, many tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts accumulated in direct contact with alkaline phosphatase (ALP)--or receptor activator of NF-kappaB ligand (RANKL)-positive osteoblastic cells, indicating the osteoclastogenesis. On the other hand, osteoclasts express CD44 while osteopontin was abundant in the stromal tissue of tumor nests. Therefore, mediating its affinity for CD44, osteopontin may serve to facilitate osteoclastic migration. We review the histopathological microenvironment featuring osteoclastic bone resorption, angiogenesis and matrix degradation, which appears to facilitate proliferation of tumor cells after the onset of bone metastasis.
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PMID:[Histopathological observations on osteolytic bone metastasis]. 1658 9

Osteoclast function is important in the development of renal osteodystrophy (ROD). Osteoclast activity is modulated by the osteoprotegerin ligand-osteoprotegerin (OPGL/OPG) system. In the present study, we checked levels of serum OPG and soluble OPGL in dialyzed patients and correlated those levels with routinely measured parameters of bone metabolism. The study was carried out in 39 patients on hemodialysis (HD) and 29 on peritoneal dialysis (PD). The control group included 13 healthy volunteers. Patients on HD had lower OPGL (p = 0.027) and higher OPG (p = 0.000) levels than control subjects did [OPGL: 0.6 pmol/L (median) and 0.0 - 10.0 pmolL (range) vs. 1.9 pmo1/L (median) and 0.0 - 10.5 pmol/L (range); OPG: 7.7 pmol/L (median) and 0.9 - 16.5 pmol/L (range) vs. 2.2 pmol/L (median) and 1.0- 3.9 pmol/L (range)]. Patients on PD differed from controls only in OPG level [4.0 pmol/L (median) and 2.1 - 13.4 pmol/L (range), p = 0.043]. Patients on HD and on PD both had a lower OPGL/OPG ratio than did the control subjects [HD: 0.09 (median) and 0.00 - 1.45 (range), p = 0.000; PD: 0.35 (median) and 0.00 - 3.89 (range), p = 0.018; controls: 1.07 (median) and 0.00 - 5.14 (range)]. Patients on HD did not differ from patients on PD in levels of OPGL and OPGL/OPG, but they had a higher OPG level (p = 0.001). Patients on HD also showed significantly higher total alkaline phosphatase (ALP) activity and higher inorganic phosphate (iP), but lower total calcium and blood pH. In PD patients, OPGL and OPG both correlated with pH (OPGL positively and OPG negatively). In HD patients, OPGL showed a positive correlation with ALP and a negative correlation with calcium; OPG correlated positively with iP In 36 patients on HD (92.3%) and 15 patients on PD (51.7%), OPG was elevated above the normal value. Differences in serum OPG and OPGL/OPG ratio between groups of dialyzed patients and of control subjects indicate that ROD is more advanced in HD patients than in PD patients. Higher serum OPG and lower serum OPGL in the HD group is probably an effect of higher osteoclast activity. In about 50% of PD patients, osteoclast function is also disturbed, as indicated by elevated OPG levels.
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PMID:Using the ratio of serum osteoprotegerin ligand to osteoprotegerin to evaluate renal osteodystrophy in dialysis patients. 1668 16

Genistein and parathyroid hormone (PTH) are anabolic agents that stimulate bone formation through their direct actions in osteoblastic cells. In the present study, we aimed to determine whether genistein modulates the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition. The present results showed that genistein (10(-8) to 10(-6) m) induced alkaline phosphatase (ALP) activity and osteoprotegrin (OPG) expression in SaOS-2 cells in a dose-dependent manner. These effects could be completely abolished by co-treatment with oestrogen antagonist ICI 182780 (7alpha-[9-[(4,4,5,5,5-pentafluoropentyl)sulfonyl]nonyl]-estra-1,3,5(10)-triene-3,17beta-diol). Genistein (at 1 microM) could stimulate the mRNA expression of receptor activator of NF-kappaB ligand (RANKL). As OPG and RANKL are known to modulate osteoclastogenesis, the ability of genistein to modulate OPG and RANKL expression in SaOS-2 cells suggested that it might modulate osteoclastogenesis through its direct actions on osteoblastic cells. PTH (at 10 nM) stimulated ALP activity, induced RANKL mRNA expression and suppressed OPG mRNA expression in SaOS-2 cells, confirming its bi-directional effects on osteoblastic cells. Pre-treatment of SaOS-2 cells with genistein and oestrogen not only enhanced PTH-induced ALP activity, but also attenuated PTH up regulation of RANKL mRNA expression and PTH down regulation of OPG mRNA expression. Taken together, the present study provides the first evidence that genistein could modulate the actions of PTH in human osteoblastic SaOS-2 cells in an oestrogen-depleted condition.
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PMID:Genistein modulates the effects of parathyroid hormone in human osteoblastic SaOS-2 cells. 1676 24

Disseminated carcinimatosis of the bone marrow is accompanied by solid tumors, and gastric cancer accounts for the majority. The prognosis of this condition is poor, however, the pathogenesis for wide-spread bone lesions has yet to be elucidated. In 9 patients with gastric cancer demonstrating disseminated carcinomatosis of the bone marrow, the characteristic clinicopathological features were examined. Immunohistochemistry for receptor activator of NF-kappaB ligand (RANKL) and parathyroid hormone-related protein was also performed on gastric cancer tissue and bone marrow specimens to identify the factors responsible for the occurrence of bone lesions in patients presenting with this condition. The characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer include a yonger patient age, an elevation of serum alkaline phosphatase and/or lactate dehydrogenase levels, wide-spread bone metastases with osteolytic bone destruction, a low incidence of hypercalcemia and a histological gastric cancer type of either signet ring cell carcinoma or poorly diffentiated adenocarcinoma. The expression of RANKL, which is one of the master regulators of osteoclastic bone resorption in bone metastasis, was also found in gastric cancer cells obtained from such patients. The RANKL expressed in gastric cancer may therefore play a critical role in the promotion of osteoclast formation, which has been suggested to be involved in the pathogenesis of bone lesions.
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PMID:Characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer: the pathogenesis of bone destruction. 1696 87

Estrogen replacement therapy has been shown to reduce postmenopausal osteoporosis. In the present study, we examined the effects of the phytoestrogen coumestrol on neonatal and adult osteoblasts metabolism. Two different sources of osteoblast cells (neonatal mice calvaria and adult mice long bone) cultures were used in this study. The effects of coumestrol on the cellular activities were analyzed by the mitochondrial tetrazolium (MTT) assay, secretion of alkaline phosphatase (ALP), intracellular calcium content (Ca), and the gene expression of bone matrix protein, estrogen receptors (ER-alpha, ER-beta), and osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL). The results showed that the proliferation of neonatal mice osteoblast cells was enhanced by treatment of coumestrol. In the presence of 10(-9)M coumestrol, the osteoblast proliferation attained 139.5% of the control and that the coumestrol can increase the intracellular calcium contents. Type I collagen gene expression was upregulated 167% at the 1st day's culture; ALP gene expression was upregulated 360% at the 7th day's culture; while the osteocalcin gene expression was upregulated 222% at the 14th day's culture. When adult mice osteoblasts were cultured in the presence of 10(-9)M coumestrol, the osteoblasts population increased significantly earlier and attained its maximal effect at the 21st day's culture with 207.4% of control group. The content of ER-beta and osteoprotegerin secretion by neonatal mice control cells gradually increased during osteoblasts differentiation, whereas the ER-alpha and OPGL content were decreased in this study. The cellular responses to the estradiol and counmestrol were quite different in the osteoblasts derived from different age.
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PMID:Effects of coumestrol on neonatal and adult mice osteoblasts activities. 1712 Feb 6

This study aimed to evaluate the ability of the health food supplement Cordyceps sinensis (CS) to ameliorate suppressive effects of chemotherapy on bone marrow function as a model for cancer treatment. Mice were treated with Taxol (17 mg/kg body wt) one day before oral administration of a hot-water extract of CS (50 mg/kg daily) that was given daily for 3 weeks. White blood cell counts in peripheral blood of mice receiving Taxol were at 50% of normal levels on day 28 but had recovered completely in mice treated with CS. In vitro assays showed that CS enhanced the colony-forming ability of both granulocyte macrophage colony forming unit (GM-CFU) and osteogenic cells from bone marrow preparations and promoted the differentiation of bone marrow mesenchymal stromal cells into adipocytes, alkaline phosphatase-positive osteoblasts, and bone tissue. This result could be attributed to enhanced expression of Cbfa1 (core binding factor a) and BMP-2 (bone morphogenetic protein) with concurrent suppression of ODF (osteoclast differentiation factor/RANK [receptor activator of NF-kappaB]) ligand. In summary, CS enhances recovery of mice from leukopenia caused by Taxol treatment. It appears to do so by protecting both hematopoietic progenitor cells directly and the bone marrow stem cell niche through its effects on osteoblast differentiation.
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PMID:Cordyceps sinensis health supplement enhances recovery from taxol-induced leukopenia. 1836 34

In this study we have developed Ca(3)ZrSi(2)O(9) (Baghdadite) ceramics by incorporating Zirconium in Ca-Si system and determined their biological properties. Ca(3)ZrSi(2)O(9) ceramics possess apatite-formation ability in simulated body fluid, indicating their potential bioactivity. The response of human osteoblast like cells (HOB), osteoclast and endothelial cells when cultured on Ca(3)ZrSi(2)O(9) ceramics was investigated. Scanning electron microscopy and immunofluorescence studies demonstrated that this material supports HOB cell attachment with organized cytoskeleton structure. Compared to CaSiO(3), Ca(3)ZrSi(2)O(9) ceramics induced increased HOB proliferation and differentiation as shown by increased methyltetrazidium salt (MTS), alkaline phosphatase activity, and mRNA expression levels of bone-related genes (Collagen type I, alkaline phosphatase, Bone Sialoprotein, receptor activator of NF-kappaB ligand and osteoprotegerin). Ca(3)ZrSi(2)O(9) ceramics supported the fusion of monocytes to form functional osteoclasts with their characteristic features of f-actin ring structures and the expression of alpha(v)beta(3) integrin consistent with functional activity. Osteoclasts cultured on Ca(3)ZrSi(2)O(9) expressed increased levels of osteoclast-related genes; Cathepsin K, Carbonic Anhydrase II, Matrix metalloproteinase-9, receptor activator of NF-kappaB and Calcitonin Receptor, consistent with the formation of functional osteoclasts. In addition to HOB and osteoclasts, Ca(3)ZrSi(2)O(9) supported the attachment of endothelial cells, which expressed the endothelial cell markers; ZO-1 and VE-Cadherin. Results presented here indicate that Ca(3)ZrSi(2)O(9) ceramics have the potential for applications in bone tissue regeneration.
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PMID:The responses of osteoblasts, osteoclasts and endothelial cells to zirconium modified calcium-silicate-based ceramic. 1875 93

To clarify the mechanisms of bone destruction associated with bone metastases, we studied an animal model in which inoculation of MDA-MB-231 human breast cancer cells into the left cardiac ventricle of female nude mice causes osteolytic lesions in bone using morphological techniques. On the bone surfaces facing the metastatic tumor cells, there existed many tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. TRAP-positive mononuclear osteoclast precursor cells were also observed in the tumor nests. Immunohistochemical studies showed that the cancer cells produced parathyroid hormone-related protein (PTHrP) but not receptor activator of NF-kappaB ligand (RANKL). Histochemical and immunohistochemical examinations demonstrated that alkaline phosphatase and RANKL-positive stromal cells were frequently adjacent to TRAP-positive osteoclast-like cells. Immunoelectron microscopic observation revealed that osteoclast-like cells were in contact with RANKL-positive stromal cells. MDA-MB-231 cells and osteoclast-like cells in the tumor nests showed CD44-positive reactivity on their plasma membranes. Hyaluronan (HA) and osteopontin (OPN), the ligands for CD44, were occasionally colocalized with CD44. These results suggest that tumor-producing osteoclastogenic factors, including PTHrP, upregulate RANKL expression in bone marrow stromal cells, which in turn stimulates the differentiation and activation of osteoclasts, leading to the progression of bone destruction in the bone metastases of MDA-MB-231 cells. Because the interactions between CD44 and its ligands, HA and OPN, have been shown to upregulate osteoclast differentiation and function, in addition to the cell-cell interactions mediated by RANK and RANKL, the cell-matrix interactions mediated by these molecules may also contribute to the progression of osteoclastic bone destruction.
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PMID:Involvement of cell-cell and cell-matrix interactions in bone destruction induced by metastatic MDA-MB-231 human breast cancer cells in nude mice. 1897 65

Bone-forming osteoblasts and bone-resorbing osteoclasts play an important role during maintenance, adaptation and healing of bone, and both cell types are influenced by physical activity. The aim of the present study was to investigate the effect of a narrow mechanical stimulation window on osteoblast- and osteoclast-like cells. Primary human cells were cultured on a bone-like structure (dentine) and three-point bending with approximately 1,100 microstrain was applied to the dentine at varying frequencies (0.1 and 0.3 Hz) and duration (1, 3 and 5 min daily over 5 days) resulting in different patterns of mechanical stimulation of osteoblast- and osteoclast-like cells. The longest stimulation (5 min at 0.1 Hz) induced a significant increase in osteoblast alkaline phosphatase activity and a significant decrease in osteoprotegerin (OPG) production, and resulted in a significant increase in the soluble receptor activator of NF-kappaB ligand (sRANKL)/OPG ratio towards sRANKL in comparison to the unstimulated osteoblast-like cells. All stimulations caused a significant decrease in collagen type 1 synthesis. Stimulation for 1 min at 0.3 Hz decreased the fusion and resorption activity of the osteoclast-like cells. These results demonstrate a direct effect of mechanical stimuli on osteoblast-like cells as well as on osteoclast formation and activity in vitro. The change in the sRANKL/OPG ratio towards the stimulation of osteoclastogenesis stresses the necessity to investigate the effect of the same stimulation parameter on the co-culture of both cell types.
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PMID:Effect of mechanical stimulation on osteoblast- and osteoclast-like cells in vitro. 1903 79

Bone is remodeled constantly throughout life by bone-resorbing osteoclasts and bone-forming osteoblasts. To maintain bone volume and quality, differentiation of osteoclasts and osteoblasts is tightly regulated through communication between and within these two cell lineages. Previously we reported that cell-cell interaction mediated by ephrinB2 ligand on osteoclasts and EphB4 receptor on osteoblasts generates bidirectional anti-osteoclastogenic and pro-osteoblastogenic signals into respective cells and presumably facilitates transition from bone resorption to bone formation. Here we show that bidirectional ephrinA2-EphA2 signaling regulates bone remodeling at the initiation phase. EphrinA2 expression was rapidly induced by receptor activator of NF-kappaB ligand in osteoclast precursors; this was dependent on the transcription factor c-Fos but independent of the c-Fos target gene product NFATc1. Receptor EphA2 was expressed in osteoclast precursors and osteoblasts. Overexpression experiments revealed that both ephrinA2 and EphA2 in osteoclast precursors enhanced differentiation of multinucleated osteoclasts and that phospholipase Cgamma2 may mediate ephrinA2 reverse signaling. Moreover, ephrinA2 on osteoclasts was cleaved by metalloproteinases, and ephrinA2 released in the culture medium enhanced osteoclastogenesis. Interestingly, differentiation of osteoblasts lacking EphA2 was enhanced along with alkaline phosphatase, Runx2, and Osterix expression, indicating that EphA2 on osteoblasts generates anti-osteoblastogenic signals presumably by up-regulating RhoA activity. Therefore, ephrinA2-EphA2 interaction facilitates the initiation phase of bone remodeling by enhancing osteoclast differentiation and suppressing osteoblast differentiation.
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PMID:Bidirectional signaling through ephrinA2-EphA2 enhances osteoclastogenesis and suppresses osteoblastogenesis. 1929 12


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