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)

OST-6 (OsteoCare), a herbomineral formulation, was evaluated for its inhibitory effect on the progress of bone loss induced by ovariectomy in rats. Ovariectomized (Ovx) rats were administered with OST-6 at 250 and 500 mg/kg b.wt., orally daily for 90 days. On 91st day, ovariectomized rats showed reduced bone mineral content and increased serum alkaline phosphatase levels, excretion of urinary calcium and pyridinium cross-links levels. Histologically, bone sections revealed narrowed and disappearance of trabeculae and widened medullary spaces. The total numbers of Tartrate-resistant acid phosphatase (TRAP) positive cells were significantly increased both in-vivo and in-vitro methods. OST-6, at a dose of 500 mg/kg, significantly improved bone mineral contents, serum alkaline phosphatase levels, reduced the elevated urinary calcium and pyridinium cross-links excretion, number of TRAP positive cells and reversal of the above mentioned histological features. These results indicate the usefulness of OST-6 in the management of osteoporosis in a natural way through herbal resources.
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PMID:The beneficial effect of OST-6 (OsteoCare), a herbomineral formulation, in experimental osteoporosis. 1141 12

The effect of low molecular weight heparin (LMWH) on serum lipid profile in hemodialysis remains controversial and its effect on bone metabolism has not been studied. A crossover study was conducted in 40 patients on stable hemodialysis using unfractionated heparin (UFH) for more than 24 months. These patients were then treated with a LMWH (nadroparin-Ca) for 8 months during hemodialysis and subsequently switched back to UFH for 12 months. Serum lipid profile, biochemical markers for bone metabolism, and bone densitometry (BMD) were monitored at four-month intervals while all medications remained unchanged. Cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), lipoprotein(a) (Lp(a)), apolipoprotein B (Apo B) were raised in 35%, 29%, 12%, 24% and 24% of patients respectively. High-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 (Apo A-1) were reduced in 47% and 9% of patients. Bone-specific alkaline phosphatase (BALP) and intact osteocalcin (OSC), both reflecting osteoblastic activity, were raised in 65% and 94% of patients. Tartrate-resistant acid phosphatase (TRACP) reflecting osteoclastic activity and parathyroid hormone (PTH) were elevated in 35% and 88% of patients. Following LMWH treatment, TC, Tg, Lp(a) and Apo B were reduced by 7%, 30%, 21% and 10% respectively (p<0.05 or <0.01) while Apo A-1 were raised by 7% (p<0.01). Simultaneously, TRACP was reduced by 13% (p<0.05). These biochemical changes were detected soon after 4 months of LMWH administration. Although BMD values in our patients were lower than those of age-matched normal subjects, significant changes were not observed with LMWH treatment. After switching back to UFH for hemodialysis, these biochemical indices reverted to previous values during UFH treatment with a significant higher level in TC and Apo B while serum Apo A-1 remained elevated. Our study suggests LMWH may partially alleviate hyperlipidemia and, perhaps, osteoporosis associated with UFH administration in patients on maintenance hemodialysis.
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PMID:Effect of low molecular weight heparin on bone metabolism and hyperlipidemia in patients on maintenance hemodialysis. 1151 Sep 16

To elucidate the mechanism in disuse bone atrophy induced by skeletal unloading, we studied the indices of bone resorption and bone formation in the femur of tail-suspended rats. The duration of the suspension ranged from 1 to 14 days. Tartrate-resistant acid phosphatase mRNA, an index used to evaluate bone resorption, increased significantly more than the controls for the first 3 days of the tail-suspension experiments, compared those in controls. Osteocalcin and alkaline phosphatase, two common markers for bone formation, were also monitored. Osteocalcin mRNA started to decrease after 3 days of suspension. Five days later, alkaline phosphatase mRNA showed a decrease. Levels of both of these mRNAs remained low for the remaining suspension period. Sequential changes in the markers for bone metabolism indicate that the transient increase in bone resorption preceded the decrease in bone formation in the development of disuse bone atrophy induced by skeletal unloading.
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PMID:Changes in the markers of bone metabolism following skeletal unloading. 1154 May 41

The effects of melatonin on osteoclastic and osteoblastic cells were examined using a culture system of the goldfish scale. Tartrate-resistant acid phosphatase (TRACP) and alkaline phosphatase (ALP) were used as markers of osteoclastic and osteoblastic cells, respectively. In Earle's minimum essential medium containing melatonin (10(-9) to 10(-5) m), activities of both enzymes in scales were significantly suppressed at 6 hr after incubation (TRACP: 10(-8), 10(-6), 10(-5) m; ALP: 10(-7) to 10(-5) m), but at 18 hr only ALP activity was significantly lowered (10(-8), 10(-7) m). Estradiol-17beta (E(2)) enhanced both activities, which were significantly inhibited and brought down to the level of the controls when co-incubated with E(2) and melatonin (TRACP at 6 hr: 10(-9) to 10(-5) m; ALP at 6 hr: 10(-7) m; ALP at 18 hr: 10(-8) m). Moreover, using reverse-transcription polymerase chain reaction, the mRNA expression of the estrogen receptor (ER) and insulin-like growth factor (IGF)-1, which are related to osteoblastic growth and differentiation, was decreased in the melatonin-treated scales. These results suggest that melatonin acts directly on the scale osteoclastic and osteoblastic cells where it suppresses the ALP activity via down-regulation of ER and IGF-1 mRNAs expression. This is the first report on the function of melatonin in osteoclasts and on the suppressive effect of melatonin in osteoblasts among vertebrates.
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PMID:Melatonin suppresses osteoclastic and osteoblastic activities in the scales of goldfish. 1239 May 9

The formation of new bone during the process of bone remodeling occurs almost exclusively at sites of prior bone resorption. In an attempt to discover what regulatory pathways are utilized by osteoblasts to effect this site-specific formation event we probed components of an active bone resorption surface with an osteoblast phage expression library. In these experiments primary cultures of rat osteoblasts were used to construct a phage display library in T7 phage. Tartrate-resistant acid phosphatase (type V) (TRAP) was used as the bait in a biopanning procedure. 40 phage clones with very high affinity for TRAP were sequenced, and of the clones with multiple consensus sequences we identified a regulatory protein that modulates osteoblast differentiation. This protein is the TGFbeta receptor-interacting protein (TRIP-1). Our data demonstrate that TRAP activation of TRIP-1 evokes a TGFbeta-like differentiation process. Specifically, TRIP-1 activation increases the activity and expression of osteoblast alkaline phosphatase, osteoprotegerin, collagen, and Runx2. Moreover, we show that TRAP interacts with TRIP intracellularly, that activation of the TGFbeta type II receptor by TRIP-1 occurs in the presence of TRAP and that the differentiation process is mediated through the Smad2/3 pathway. A final experiment demonstrates that osteoblasts, when cultured in osteoclast lacunae containing TRAP, rapidly and specifically differentiate into a mature bone-forming phenotype. We hypothesize that binding to TRAP may be one mechanism by which the full osteoblast phenotype is expressed during the process of bone remodeling.
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PMID:A phage display technique identifies a novel regulator of cell differentiation. 1240 89

Tartrate-resistant acid phosphatase (TRAP) of Amoeba proteus (strain B) was represented by 3 of 6 bands (= electromorphs) revealed after disc-electrophoresis in polyacrylamide gels with the use of 2-naphthyl phosphate as a substrate at pH 4.0. The presence of MgCl2, CaCl2 or ZnCl2 (50 mM) in the incubation mixture used for gel staining stimulated activities of all 3 TRAP electromorphs or of two of them (in the case of ZnCl2). When gels were treated with MgCl2, CaCl2 or ZnCl2 (10 and 100 mM, 30 min) before their staining activity of TRAP electromorphs also increased. But unlike 1 M MgCl2 or 1 M CaCl2, 1 M ZnCl2 partly inactivated two of the three TRAP electromorphs. EDTA and EGTA (5 mM), and H2O2 (10 mM) completely inhibited TRAP electromorphs after gel treatment for 10, 20 and 30 min, resp. Of 5 tested ions (Mg2+, Ca2+, Fe2+, Fe3+ and Zn2+), only the latter reactivated the TRAP electromorphs previously inactivated by EDTA or EGTA treatment. In addition, after EDTA inactivation, TRAP electromorphs were reactivated better than after EGTA. The resistance of TRAP electromorphs to okadaic acid and phosphatase inhibitor cocktail 1 used in different concentrations is indicative of the absence of PP1 and PP2A among these electromorphs. Mg2+, Ca2+ and Zn2+ dependence of TRAP activity, and the resistance of its electromorphs to vanadate and phosphatase inhibitor cocktail 2 prevents these electromorphs from being classified as PTP. It is suggested that the active center of A. proteus TRAP contains zinc ion, which is essential for catalytic activity of the enzyme. Thus, TRAP of these amoebae is metallophosphatase showing phosphomonoesterase activity in acidic medium. This metalloenzyme differs from both mammalian tartrate-resistant PAPs and tartrate-resistant metallophosphatase of Rana esculenta.
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PMID:[Tartrate-resistant acid phosphatase in free-living Amoeba proteus]. 1256 34

Tartrate-resistant acid phosphatase isoform-5b (TRACP-5b), a new marker reflecting osteoclast activity, and osteoprotegerin (OPG) were measured in 121 patients with multiple myeloma (MM) at diagnosis, and in 63 of them during pamidronate administration, to define their correlation with the extent of bone disease and disease activity in MM. Radiographic evaluation of the skeleton, measurement of other markers of bone remodelling, including N-terminal cross-linking telopeptide of type-I collagen (NTX), bone alkaline phosphatase and osteocalcin and of markers of disease activity (beta2-microglobulin, paraprotein, interleukin-6 (IL-6), were also performed. Levels of TRACP-5b were increased (p <.0001), while OPG was decreased in MM patients compared to controls (p <.01). TRACP-5b levels were associated with the radiographically assessed severity of bone disease (p <.0001) as well as with levels of NTX, IL-6 and beta2-microglobulin (p <.001, for each biochemical parameter, respectively). The combination of pamidronate with VAD-chemotherapy produced a reduction in TRACP-5b, NTX, IL-6, paraprotein and beta2-microglobulin levels from the 2nd month of treatment, with no effect on bone formation and OPG. A strong correlation was observed between changes in TRACP-5b and changes in NTX, IL-6 and beta2-microglobulin, while TRACP-5b predicted the disease progression in 5 patients. These findings suggest that TRACP-5b is increased in MM, reflects the extent of myeloma bone disease and may have a predictive value. TRACP-5b has also proved to be very useful for monitoring antimyeloma treatment, which had no effect on OPG levels.
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PMID:Tartrate-resistant acid phosphatase isoform 5b: a novel serum marker for monitoring bone disease in multiple myeloma. 1284 88

The direct effect of bisphenol A on osteoclasts and osteoblasts was examined using a culture system of goldfish scales. Tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) were used as markers of osteoclasts and osteoblasts, respectively. Bisphenol A (10(5) M) significantly suppressed both TRAP and ALP activities. These data were reproduced in an in vivo experiment. From an analysis of a reverse transcription-polymerase chain reaction in the in vitro-cultured scales, it was demonstrated that the insulin-like growth factor (IGF)-1 mRNA expression decreased by a bisphenol A treatment. On the other hand, 17beta-estradiol (E(2)) stimulated both TRAP and ALP activities and did not change IGF-1 mRNA expression, suggesting that bisphenol A has a different effect from E(2) on bone metabolism. This study is the first to demonstrate that bisphenol A functions to suppress directly osteoblasts and osteoclasts among vertebrates, which strongly suggests that this scale in an in vitro assay system can be utilized for the evaluation of the effects of endocrine disrupters on bone cells.
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PMID:Bisphenol A suppresses osteoclastic and osteoblastic activities in the cultured scales of goldfish. 1292 93

Parathyroid hormone-related peptide (PTHrP) induces pathological bone resorption in an endocrine manner, resulting in hypercalcemia of malignancy. However, the histopathological aspect of the action of PTHrP secreted by tumor cells on bone resorption has not well been documented. Therefore, we studied cell-cell interactions between bone cells, stromal cells, and PTHrP-secreting tumor cells (EC-GI-10) morphologically. Tumor cells injected subcutaneously into the parietal region formed a tumor mass, invading the bone marrow. The tumor mass was surrounded by a membrane structure consisting of stromal cells. These stromal cells were positive for alkaline phosphatase (ALPase). Tartrate-resistant acid phosphatase (TRAPase)-positive osteoclasts were localized close to the ALPase-positive cells, and numerous osteoclasts were observed on the neighboring bone surfaces. PTHrP, vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-9 were detected in the tumor cells. Using RT-PCR, expression of interleukin (IL)-1Alpha, IL-1Beta, and PTHrP, which are strong bone resorption factors, was detected in the tumor cells. Some ALPase-positive cells localizing on the neighboring bone surfaces and endothelial cells revealed PTH/PTHrP receptor immunoreactivity. Ultrastructurally, numerous blood vessels were observed between the tumor nests and the stromal cells. The nests were surrounded by a basement membrane, but it was discontinuous, therefore permitting direct contact between the tumor cells and the stromal cells. These results indicate that PTHrP secreted by tumor cells appears to stimulate osteoclast differentiation and bone resorption in a paracrine manner through PTH/PTHrP receptor-immunopositive cells. IL-1Alpha, IL-1Beta, VEGF, and MMP-9 may also be involved in facilitating osteoclast formation and the subsequent bone resorption.
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PMID:Ultrastructural and cytobiological studies on possible interactions between PTHrP-secreting tumor cells, stromal cells, and bone cells. 1458 91

Osteoclast differentiation in the process of ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2) was examined to clarify the relationship between osteoclast development and rhBMP-2-induced bone formation. A combination of rhBMP-2 with a porous microsphere (PMS) and blood clot was implanted subcutaneously on the bilateral chest muscles of rats. Tartrate-resistant acid phosphatase (TRAPase) activity, cathepsin K (cath K), and calcitonin receptor (CTR), as markers of osteoclasts and their precursors, were examined using enzyme and immunohistochemical analysis up to 7 days after implantation. Mononuclear cells positive for TRAPase, cath K, and CTR first appeared on day 3 in connective tissue surrounding the PMS after implantation of rhBMP-2. Simultaneously, alkaline phosphatase activity became detectable in mesenchymal cells in the connective tissue. Electron microscopy demonstrated some mononuclear cells with abundant mitochondria and poorly developed rough endoplasmic reticulum in the proximity of mesenchymal cells. However, there was no evidence of cartilage or bone matrix formation on day 3. Osteoclasts in various stages of development, classified by the pattern of immunoreactivity for cath K, were observed by day 7. The polarized intracellular distribution of cath K was found only in osteoclasts attached to bone matrix. In conclusion, we have demonstrated for the first time the appearance of osteoclast precursors before bone matrix formation induced by rhBMP-2, suggesting that bone matrix is not a prerequisite for osteoclast precursor recruitment. Furthermore, we suggest that differentiation into polarized functional osteoclasts is accomplished when the osteoclasts attach to the bone matrix.
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PMID:Osteoclast differentiation in ectopic bone formation induced by recombinant human bone morphogenetic protein 2 (rhBMP-2). 1458 92


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