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)

The classic oral features of hypophosphatasia, namely, premature tooth loss and large pulp spaces, were found in a young adult woman with bone and joint pains. A study of 22 family members revealed several with dental abnormalities such as abnormal enamel, dentin, or cementum formation, decreased mandibular bone density, and abnormally large pulp spaces. Only the propositus' sister fulfilled the biochemical criteria for hypophosphatasia. Biochemical examination of an extracted tooth from this sister showed phosphate and alkaline phosphatase values that were 7 to 10 times lower than normal and reduced concentrations of the essential cofactors Zn++ and Co++. The spectrum of dental abnormalities is reviewed. This family study reveals that enamel hypoplasia, increased pulp spaces, and premature tooth loss are present not only in the deciduous but also in the permanent dentition. These findings should draw the dentist's attention to this condition.
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PMID:Dental aspects of hypophosphatasia: a case report, family study, and literature review. 265 97

This report concerns a family showing both the lethal and mild form of hypophosphatasia in half-sibs. In addition, several other paternal family members with the mild form are documented. The lethal form is characterized by extremely low to absent alkaline phosphatase activity in serum with hypomineralization of the skeleton, whereas mildly affected individuals have enzyme levels intermediate between normal and lethal states. On the basis of this pedigree and because the mildly affected individuals have both biochemical abnormalities and the clinical phenotype of premature tooth loss, we prefer to designate hypophosphatasia as a dominant trait affecting both osteogenesis and cementogenesis which has mild clinical expression in the heterozygote but lethality in the homozygote. This situation resembles the dominantly inherited enzymopathy acute intermittent porphyria.
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PMID:Lethal and mild hypophosphatasia in half-sibs. 713 Mar 55

It is believed that the degree of periodontal tissue breakdown and tooth loss increase with age. In periodontal tissues which are gingiva, periodontal ligament (PL), alveolar bone and tooth cementum, the PL which is soft connective tissue, lies between the tooth cementum and alveolar bone, having the primary function of tooth support, and maintaining the homeostasis of supporting tissues, as well as providing the healing process. We therefore investigated the effects of in vitro cellular aging on alkaline phosphatase (ALP), cathepsin activities and collagen secretion from human PL cells obtained from 18-23 year-old patients' teeth. ALP, cathepsin activities and collagen secretion may play important roles in the remodeling and maintaining of periodontal tissues. To investigate the life span of PL cells, the cells were sequentially subcultivated. The maximum population doubling level of the PL cells in the present experiment was 22-25 passages. Investigating some important biological activities of the PL cells at different passage levels (6-7, 30% of life span to 17-20, 75% of life span), ALP activity and collagen secretion were found to have significantly decreased while cathepsin B and L activities significantly increased with cellular aging. Since these biological activities in human PL cells tend to be more catabolic with increase in cellular aging, the increase in periodontal breakdown with age may be partly related to the catabolic changes of the PL cells themselves.
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PMID:Effects of in vitro cellular aging on alkaline phosphatase, cathepsin activities and collagen secretion of human periodontal ligament derived cells. 905 41

We describe a new familial metabolic bone disease characterized by expanding hyperostotic long bones, early onset deafness, premature tooth loss, and episodic hypercalcemia. The condition affects a mother and daughter studied at the age of 36 years and 11 years, respectively. Both individuals lost all hearing in early childhood and suffered premature shedding of teeth. Skeletal pains began just before puberty. Swelling and aching of most middle phalanges in the hands is an especially troublesome manifestation. The mother also had episodes of symptomatic hypercalcemia first documented in late childhood and subsequently during intercurrent illness and postpartum lactation. Radiographs show hyperostosis and/or osteosclerosis predominantly in the skull and appendicular skeleton. Long bones also are expanded considerably, especially the middle phalanges in the fingers. The mother's skeletal abnormalities are more severe. Biochemical parameters of bone turnover, including serum alkaline phosphatase (ALP) activity, are elevated substantially. In the proposita, dynamic histomorphometry of nondecalcified sections of iliac crest revealed rapid skeletal remodeling. In the mother, who had been treated with bisphosphonates, electron microscopy (EM) showed disorganized collagen bundles as well as necrotic and apoptotic bone cells but no osteocytic osteolysis. Measles virus gene transcripts were not detected in peripheral blood monocytes. Karyotyping was normal, 46,XX. Hyperphosphatasia with bone disease previously has been reported as either a sporadic or autosomal recessive condition. Expansile skeletal hyperphosphatasia (ESH) is probably inherited as an autosomal dominant trait with a high degree of penetrance.
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PMID:Expansile skeletal hyperphosphatasia: a new familial metabolic bone disease. 1112 98

Three different insertion mutations in the TNFRSF11A gene affecting the signal peptide of RANK have been described. An 18-bp duplication at position 84 (84dup18) is associated with the clinical syndrome of familial expansile osteolysis (FEO), whereas a 15-bp duplication at the same site (84dup15) causes the syndrome of expansile skeletal hyperphosphatasia (ESH). Here we report the phenotype of patients harboring a 27-bp duplication at position 75 (75dup27) in RANK. Affected individuals had hearing impairment and tooth loss beginning in the second or third decade. Radiographs of affected bones showed lytic and sclerotic lesions with bony enlargement and deformity. Serum alkaline phosphatase levels were elevated between 2 and 17 times above the normal range. Most patients had pelvic and skull involvement, and all had involvement of the mandible and maxilla. Most patients also had bony enlargement of the small joints of the hands, and one developed hypercalcemia during a period of immobilization. We conclude that the 75dup27 mutation of RANK causes a Paget's disease of bone-like phenotype that is distinct from, but which overlaps with, FEO and ESH. A particularly striking feature was involvement of the mandible and maxilla, but it remains to be seen if this is a specific feature of the 75dup27 mutation until further kindreds with this mutation are reported.
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PMID:Phenotypic characterization of early onset Paget's disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. 1292 27

Maintenance of alveolar bone width and height following tooth loss is essential with regard to the restoration of missing teeth with endosseous dental implants or prosthodontics approaches. A various amount of alveolar ridge resorption is likely to occur after tooth extraction at the buccal and lingual alveolar bone plates. Bisphosphonates, alendronate, is well known for its potent inhibition of osteoclast-mediated bone resorption. The objective of this study was to examine the inhibitory effect of alendronate on alveolar bone resorption following tooth extraction in rats. Male Wistar Albino rats were divided into three groups: baseline group, saline-treated group and alendronate-treated group. The saline-treated group was administered with daily saline solution for 2 and 4 weeks respectively while the alendronate-treated group was given a daily amount of 0.25 mg/kg alendronate subcutaneously for the same periods. The level of urinary calcium, creatinine, and serum calcium, alkaline phosphatase and phosphate were measured. Serum alkaline phosphatase level was measured as a marker of osteoblastic activity. Histopathological sections of 4 microm thickness were obtained from the right first mandibular molar region in a bucco-lingual direction. The number of osteoclasts, osteoblasts, and haversian canals, the number and size of resorptive lacunae, and osteoid formation were evaluated histopathologically. The mean thickness of buccal and lingual alveolar bone was measured. In the alendronate-treated group, both buccal and lingual alveolar bone volume reduction was significantly less than the saline treated group. Significant reduction in serum and urinary calcium levels and the number of osteoclasts revealed the pronounced suppression of bone resorption in the alendronate-treated group.
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PMID:The effect of alendronate on resorption of the alveolar bone following tooth extraction. 1528 13

Hypophosphatasia is a rare inherited disorder characterized by defective bone and tooth mineralization, and deficiency of serum and bone alkaline phosphatase activity. The frequency of the disease has been estimated to be one in 100 000 for severe forms, but mild forms of hypophosphatasia may be more common. The symptoms are highly variable in their clinical expression, which ranges from stillbirth without mineralized bone to early tooth loss without bone symptoms. The transmission of severe forms is autosomal recessive, while milder forms may be transmitted as dominant or recessive autosomal traits. The diagnosis is based on serum alkaline phosphatase assay and molecular analysis of the liver/bone/kidney alkaline phosphatase gene (ALPL). Currently, there is no treatment for the disease. Over the past 10 years, great progress has been made in understanding the structure of tissue non-specific alkaline phosphatase, its function in bone mineralization, and the effect of ALPL mutations responsible for hypophosphatasia.
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PMID:Hypophosphatasia. 1832 85

Mesenchymal stem cell (MSC)-mediated tissue regeneration offers opportunities to regenerate a bio-root and its associated periodontal tissues to restore tooth loss. Previously, we proved that the apical end of developing root was acting as a promising candidate cell source for root/periodontal tissue (R/PT) regeneration. In the present study, we investigated the properties of periapical follicle stem cells (PAFSCs) isolated from the apical end of developing root of human third molars at the root-developing stage and evaluated the potential application of these cells for cementum/periodontal ligament (PDL) regeneration and bio-root engineering. Putative PAFSCs were isolated and subcultured until 20th passage. Cell characteristics of PAFSCs at early or late passage were evaluated and compared with periodontal ligament stem cells (PDLSCs) via a series of histological, cellular, and molecular analyses. PAFSCs at early passage presented crucial stem cell properties and showed a higher proliferation rate than PDLSCs in vitro. Meanwhile, PAFSCs also showed the tissue-regenerative capacity to produce a typical cementum/PDL-like complex in vivo. During long-term passage, both cell populations changed in morphology and gradually lost their stem cell properties. The alkaline phosphatase (ALP) activity and expression of mineralization-related genes markedly declined as more passages were carried out, which might lead to the loss of tissue-regenerative capacity of these 2 groups of cells in vivo. Our findings suggest that developing tissue-derived PAFSCs are a distinctive cell population from PDLSCs and might be a promising candidate for bio-root engineering.
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PMID:Periapical follicle stem cell: a promising candidate for cementum/periodontal ligament regeneration and bio-root engineering. 1999 54

Hypophosphatasia (HPP) occurs from loss-of-function mutation in the tissue-non-specific alkaline phosphatase (TNALP) gene, resulting in extracellular pyrophosphate accumulation that inhibits skeletal and dental mineralization. TNALP-null mice (Akp2(-/-)) phenocopy human infantile hypophosphatasia; they develop rickets at 1 week of age, and die before being weaned, having severe skeletal and dental hypomineralization and episodes of apnea and vitamin B(6)-responsive seizures. Delay and defects in dentin mineralization, together with a deficiency in acellular cementum, are characteristic. We report the prevention of these dental abnormalities in Akp2(-/-) mice receiving treatment from birth with daily injections of a mineral-targeting, human TNALP (sALP-FcD(10)). sALP-FcD(10) prevented hypomineralization of alveolar bone, dentin, and cementum as assessed by micro-computed tomography and histology. Osteopontin--a marker of acellular cementum--was immuno-localized along root surfaces, confirming that acellular cementum, typically missing or reduced in Akp2(-/-) mice, formed normally. Our findings provide insight concerning how acellular cementum is formed on tooth surfaces to effect periodontal ligament attachment to retain teeth in their osseous alveolar sockets. Furthermore, they provide evidence that this enzyme-replacement therapy, applied early in post-natal life--where the majority of tooth root development occurs, including acellular cementum formation--could prevent the accelerated tooth loss seen in individuals with HPP.
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PMID:Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia. 2121 13

Loss of teeth increases with age or after genotoxic treatments, like head and neck radiotherapy, due to periodontium breakdown. Periodontal ligament fibroblasts represent the main cell type in this tissue and are crucial for the maintenance of homeodynamics and for its regeneration. Here, we have studied the characteristics of human periodontal ligament fibroblasts (hPDLF) that became senescent after replicative exhaustion or after exposure to ionizing radiation, as well as their ability for osteoblastic differentiation. We found that senescent hPDLF express classical markers of senescence, as well as a catabolic phenotype, as shown by the decrease in collagen type I and the increase of MMP-2 expression. In addition, we observed a considerably decreased expression of the major transcription factor for osteoblastic differentiation, i.e. Runx2, a down-regulation which was found to be p53-dependent. In accordance to the above, senescent cells have a significantly decreased alkaline phosphatase gene expression and activity, as well as a reduced ability for osteoblastic differentiation, as found by Alizarin Red staining. Interestingly, cells from both type of senescence express similar characteristics, implying analogous functions in vivo. In conclusion, senescent hPDLF express a catabolic phenotype and express a significantly decreased ability towards an osteoblastic differentiation, thus probably affecting tissue development and integrity.
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PMID:Senescent human periodontal ligament fibroblasts after replicative exhaustion or ionizing radiation have a decreased capacity towards osteoblastic differentiation. 2393 84


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