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)

To determine whether alkaline phosphatase (ALP) can cause the mineralization of collagenous matrices in vivo, bovine intestinal ALP was covalently bound to slices of guanidine-extracted demineralized bovine dentin (DDS). The preparations were implanted subcutaneously over the right half of the rat skull. Control slices not treated with the enzyme were implanted over the left half of the skull of the same animals. Specimens were harvested after periods varying from 1 to 4 wk. It was shown that ALP-coupled DDS rapidly accumulated hydroxyapatite crystals. 4 wk after implantation, the content of calcium and phosphate per microgram of hydroxyproline amounted up to 80 and 60%, respectively, of that found in normal bovine dentin. Our observations present direct evidence that ALP may play a crucial role in the induction of hydroxyapatite deposition in collagenous matrices in vivo.
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PMID:Alkaline phosphatase induces the mineralization of sheets of collagen implanted subcutaneously in the rat. 160 3

This review addresses the role of lipids and membranes in biologic calcification and examines their regulation during endochondral ossification. The close association of lipids with mineral deposition has been well established. Early observations indicated that lipids, particularly phospholipids, can not be totally extracted from calcified tissues until the tissues are decalcified. Phospholipids associated with mineral are also enriched in extracellular membrane vesicles, called matrix vesicles. Numerous studies indicate that mineral deposits in calcifying cartilage are first seen in these phosphatidylserine and alkaline phosphatase enriched vesicles and that the process of endochondral calcification of epiphyseal growth plate is possibly mediated by them. Matrix vesicles, and the phospholipids present in them, appear to be involved in initial formation of calcium hydroxyapatite crystals via the interaction of calcium and phosphate ions with phosphatidylserine to form phospholipid:Ca:Pi complexes (CPLX). CPLX is present in tissues which are undergoing initial mineral deposition but are absent from nonmineralizing tissues. Evidence suggests that CPLX resides in the interior of matrix vesicles where the earliest mineral crystals are formed in association with the vesicle membrane. More recently, it has been determined that specific membrane proteins, called proteolipids, participate in CPLX formation and hydroxyapatite deposition, in part by structuring phosphatidylserine in an appropriate conformation. Phosphatidylserine involvement in the initiation of mineralization has been extensively investigated because of its extremely high binding affinity for Ca2+. In addition to structuring a specific phospholipid environment, proteolipids may also act as ionophores, promoting export of protons and import of calcium and phosphate, both requirements of biologic calcification.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of lipids in calcification of cartilage. 267 85

Osteopontin is a phosphorylated bone matrix sialoprotein, postulated to play a regulatory role in biomineralization. The effects of a crude preparation of rat bone osteopontin and a more highly purified bovine bone osteopontin were evaluated using a gel diffusion system to measure effects of 0.1-100 micrograms/ml of this matrix protein on hydroxyapatite formation and crystal proliferation. Bovine osteopontin at concentrations greater than 25 micrograms/ml inhibited both hydroxyapatite formation and growth in a dose-dependent manner. Osteopontin at concentrations lower than 25 micrograms/ml had no detectable effect on the amount of mineral accumulated in experiments with and without pre-formed hydroxyapatite seed crystals either when initial mineral deposition was assessed at 3.5 days, or when mineral formation and growth were assessed at 5 days. There was a statistically significant dose-dependent decrease in crystal length at all concentrations tested. The rat osteopontin preparation had similar inhibitory abilities. Partial dephosphorylation of bovine osteopontin with alkaline phosphatase removed its inhibitory ability, and reduced its ability to bind calcium. The affinity of bovine osteopontin for hydroxyapatite was determined based on a Langmuir adsorption isotherm, with values of K (binding affinity) and N (number of binding sites) being 0.026 ml/microgram and 1084 micrograms/m2, respectively. The data suggest that, in this system, osteopontin is an effective inhibitor of hydroxyapatite formation and growth due to its affinity for the hydroxyapatite crystals. In this system, osteopontin, distinct from other phosphoproteins which both promote and inhibit hydroxyapatite deposition, did not enhance mineral formation at any concentration tested.
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PMID:Osteopontin-hydroxyapatite interactions in vitro: inhibition of hydroxyapatite formation and growth in a gelatin-gel. 825 66

Extracellular pyrophosphate (PPi) plays a central role in the control of normal bone mineralization since it antagonizes inorganic phosphate in the promotion of hydroxyapatite deposition. Studies using knock-out mice have established the functional importance of PPi generation via nucleotide pyrophosphatase phosphodiesterases (NPP) and of PPi transmembrane transport by the progressive ankylosis (ANK) protein. Tissue non-specific alkaline phosphatase activity counteracts this by hydrolysis of PPi to inorganic phosphate. The molecular nature and transport function of ANK are reviewed. A close parallel is drawn between the controlled mineralization of bone and the prevention of abnormal calcium crystal deposition within the kidney, especially when concentrated urine is produced. Pyrophosphate is present in urine, and ANK is expressed in the cortical collecting duct where PPi transport to both the tubular lumen and the renal interstitium may occur. Pyrophosphate may also be generated here by nucleoside triphosphate diphosphohydrolases (NTPD2 and 3) together with NPP1. Alkaline phosphatase activity is restricted to the proximal nephron, remote from these sites of PPi generation, transport and function. The physiological importance of PPi generation and transport in preventing idiopathic calcium renal stone disease and nephrocalcinosis now needs to be established.
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PMID:Renal calcium stones: insights from the control of bone mineralization. 1791 53

In contrast to physiologic biomineralization occurring in bones, teeth and otoconia in vertebrates, calcification of soft tissues occurs in many pathologic conditions. Although similarities have been noted between the two processes, and despite the important clinical consequences of ectopic calcification, the molecular mechanisms regulating ectopic calcification are poorly understood. Although calcification is mainly extracellular, intracellular calcification has been reported and might indeed contribute to pathologic calcification of soft tissues. To better understand the process of intracellular calcification as a potential origin for pathologic calcification, and to examine the role of proteoglycans in this process, we investigated a pattern of intracellular nucleation and growth of hydroxyapatite in Madin-Darby Canine Kidney (MDCK) epithelial cells using electron microscopy, secondary ion mass spectroscopy (NanoSIMS), cytochemical staining, immunolabeling and biochemical analysis. We report here that under mineralizing cell culture conditions where beta-glycerophosphate (betaGP) was added as an exogenous organic source of phosphate, betaGP-cleaving alkaline phosphatase activity increased and hydroxyapatite crystals subsequently nucleated within intracellular, membrane-bounded compartments. The small, leucine-rich proteoglycan decorin was also upregulated and associated with mineral in these cultures. Such information provides insight into the mechanisms leading to pathologic calcification and describes a process whereby hydroxyapatite deposition in cells might lead to ectopic calcification.
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PMID:Intracellular precipitation of hydroxyapatite mineral and implications for pathologic calcification. 1842 74

Pyrophosphate is an established inhibitor of hydroxyapatite deposition and crystal growth, yet when hydrolyzed into phosphate, it becomes a substrate for hydroxyapatite deposition. Pyrophosphate-generating enzyme (PC-1), Ank, and tissue nonspecific alkaline phosphatase (Tnap) are three factors that regulate extracellular pyrophosphate levels through its generation, transport, and hydrolysis. We previously showed that fibroblast growth factor 2 (FGF2) induces PC-1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre-osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre-osteoblast cultures. In contrast to Ank and Tnap that are regulated by FGF2 in multiple cell types, we found regulation of PC-1 to be selective to pre-osteoblastic cells and to require the osteoblast-related transcription factor, Runx2. Specifically, FGF2 was unable to induce PC-1 expression in Runx2-negative nonbone cells or in calvarial cells from Runx2-deficient mice. Transfection of these cells with a Runx2 expression vector restored FGF2 responsiveness. FGF2 was also shown to stimulate recruitment of Runx2 to the endogenous PC-1 promoter in MC3T3E1(C4) cells, as measured by chromatin immunoprecipitation. Taken together, our results establish that FGF2 is a specific inducer of PC-1 in pre-osteoblast cells and that FGF2 induces PC-1 expression through a mechanism involving Runx2.
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PMID:FGF2 stimulation of the pyrophosphate-generating enzyme, PC-1, in pre-osteoblast cells is mediated by RUNX2. 1904 25

We report a case of acute carpal tunnel syndrome caused by periarticular calcification (hydroxyapatite deposition disease) around the wrist joint in a 64-year-old woman. She had acute severe pain, exacerbated by wrist movements and extension of the fingers. Her full blood count, urea, electrolytes, uric acid, calcium, phosphate, alkaline phosphatase, and thyroid function levels were all within normal ranges, and her serum was negative for rheumatoid factor. Computed tomography revealed lobulated calcification close to the volar capsule. She underwent an emergency surgical decompression of the carpal tunnel under general anaesthesia within 3 hours of presentation. The flexor tendon sheaths were excised, and 'toothpaste-like' chalky material (hydroxyapatite crystals) in the capsule was removed. The pain was relieved dramatically and her median nerve function recovered. She was symptom-free at the one-year follow-up.
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PMID:Periarticular calcification causing acute carpal tunnel syndrome: a case report. 1972 Nov 61

Intimal calcification is a feature of advanced atherosclerotic disease that predicts a two- to eightfold increase in the risk of coronary events. Type I collagen promotes vascular smooth muscle cell-mediated calcification, although the mechanism by which this occurs is unknown. The discoidin domain receptor 1 (DDR1) is a collagen receptor that is emerging as a critical mediator of atherosclerosis. To determine whether DDR1 is involved in intimal calcification, we fed male Ddr1(-/-);Ldlr(-/-) and Ddr1(+/+);Ldlr(-/-) mice an atherogenic diet for 6, 12, or 24 weeks. DDR1 deficiency significantly reduced the calcium content of the aortic arch, and microcomputed tomography demonstrated a significant decrease in hydroxyapatite deposition after 24 weeks of atherogenic diet. Reduced calcification was correlated with decreases in macrophage accumulation and tumor necrosis factor alpha staining, suggesting that the reduction in calcification was in part due to decreased inflammation. The chondrogenic markers type II collagen, type X collagen, and Sox-9 were expressed within the mineralized foci. An in vitro assay performed with vascular smooth muscle cells revealed that DDR1 was required for cell-mediated calcification of the matrix, and Ddr1(+/+) smooth muscle cells expressed more alkaline phosphatase activity, whereas Ddr1(-/-) smooth muscle cells expressed elevated levels of mRNA for nucleotide pyrophosphatase phosphodiesterase 1, an inhibitor of tissue mineralization. Taken together, our results demonstrate that DDR1 mediates an important mechanism for atherosclerotic calcification.
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PMID:Discoidin domain receptor-1 deficiency attenuates atherosclerotic calcification and smooth muscle cell-mediated mineralization. 1989 47

The work was focused on the synthesis and characterization of the chitosan-g-fluorescein (CHFL) conjugate polymer as a biocompatible amphiphilic water-soluble photosensitizer, able to stimulate hydroxyapatite deposition upon visible light irradiation. Fluorescein (FL) grafting to chitosan (CH) chains was confirmed by UV-vis analysis of water solutions of FL and CHFL and by Fourier transform infrared spectroscopy (FTIR-ATR) analysis of CHFL and CH. Smooth CHFL cast films with 4 microm thickness were obtained by solvent casting. Continuous exposure to visible light for 7 days was found to activate the deposition of calcium phosphate crystals from a conventional simulated body fluid (SBF 1.0x) on the surface of CHFL cast films. EDX and FTIR-ATR analyses confirmed the apatite nature of the deposited calcium phosphate crystals. CHFL films preincubated in SBF (1.0x) solution under visible light irradiation and in the dark for 7 days were found to support the in vitro adhesion and proliferation of MG63 osteoblast-like cells (MTT viability test; 1-3 days culture time). On the other hand, the mineralization ability of MG63 osteoblast-like cells was significantly improved on CHFL films preincubated under visible light exposure (alkaline phosphatase activity (ALP) test for 1, 3, 7, and 14 days). The use of photoactive biocompatible conjugate polymer, such as CHFL, may lead to new therapeutic options in the field of bone/dental repair, exploiting the photoexcitation mechanism as a tool for biomineralization.
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PMID:Photoactive chitosan switching on bone-like apatite deposition. 2008 15

Advances in electrospun nanofibres with bioactive materials have enhanced the scope of fabricating biomimetic scaffolds for tissue engineering. The present research focuses on fabrication of polycaprolactone/aloe vera/silk fibroin nanofibrous scaffolds by electrospinning followed by hydroxyapatite deposition by calcium-phosphate dipping method for bone tissue engineering. Morphology, composition, hydrophilicity and mechanical properties of polycaprolactone/aloe vera/silk fibroin-hydroxyapatite nanofibrous scaffolds along with controls polycaprolactone and polycaprolactone/aloe vera/silk fibroin nanofibrous scaffolds were examined by field emission scanning electron microscopy, Fourier transform infrared spectroscopy, contact angle and tensile tests, respectively. Adipose-derived stem cells cultured on polycaprolactone/aloe vera/silk fibroin-hydroxyapatite nanofibrous scaffolds displayed highest cell proliferation, increased osteogenic markers expression (alkaline phosphatase and osteocalcin), osteogenic differentiation and increased mineralization in comparison with polycaprolactone control. The obtained results indicate that polycaprolactone/aloe vera/silk fibroin-hydroxyapatite nanofibrous scaffolds have appropriate physico-chemical and biological properties to be used as biomimetic scaffolds for bone tissue regeneration.
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PMID:Precipitation of hydroxyapatite on electrospun polycaprolactone/aloe vera/silk fibroin nanofibrous scaffolds for bone tissue engineering. 2428 81


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