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)

Platelet-derived growth factor (PDGF), insulin-like growth factor-I and -II (IGF-I and -II), acidic fibroblast growth factor (aFGF), basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) stimulated [125I]-deoxyuridine incorporation about 13, 6.2-, 4.6-, 3.8-, 3.1- and 1.2-fold, respectively, above control values at a concentration of 50 ng/ml. Transforming growth factor-beta (TGF-beta) decreased incorporation about 30% at the same dose. aFGF, IGF-I, IGF-II, bFGF and TGF-beta increased [35S]-sulphate incorporation 231, 71, 64, 42 and 39%, respectively, in proliferating cells, while EGF, IGF-I, TGF-beta and PDGF decreased incorporation about 30%, and aFGF increased incorporation 80% in stationary-stage culture. TGF-beta, PDGF, aFGF and bFGF caused 65-40% inhibition of alkaline phosphatase activity in proliferating and stationary cultures. These findings suggest that the proliferation of pulp cells may be stimulated mainly by PDGF and IGF-I, and the production of extracellular matrix proteoglycan may be enhanced by aFGF, IGF-I and IGF-II. Furthermore, TGF-beta, PDGF, aFGF and bFGF may regulate the differentiation of pulp cells into odontoblasts.
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PMID:The effects of growth factors on DNA synthesis, proteoglycan synthesis and alkaline phosphatase activity in bovine dental pulp cells. 137 23

Chondrocytes from chicken embryo tibia can be maintained in culture as adherent cells in Coon's modified Ham's F-12 medium supplemented with 10% FCS. In this condition, they dedifferentiate, losing type II collagen expression in favor of type I collagen synthesis. Their differentiation to hypertrophy can be obtained by transferring them to suspension culture. Differentiation is evidenced by the shift from type I to type II and type IX collagen synthesis and the following predominant expression of type X collagen, all markers of specific stages of the differentiation process. To identify the factors required for differentiation, we developed a serum-free culture system where only the addition of triiodothyronine (T3; 10(-11) M), insulin (60 ng/ml), and dexamethasone (10(-9) M) to the F-12 medium was sufficient to obtain hypertrophic chondrocytes. In this hormonal context, chondrocytes display the same changes in the pattern of protein synthesis as described above. For proper and complete cell maturation, T3 and insulin concentrations cannot be modified. Insulin cannot be substituted by insulin-like growth factor-I, but dexamethasone concentration can be decreased to 10(-12) M without chondrogenesis being impaired. In the latter case, the expression of type X collagen and its mRNA are inversely proportional to dexamethasone concentration. When ascorbic acid is added to the hormone-supplemented medium, differentiating chondrocytes organize their matrix leading to a cartilage-like structure with hypertrophic chondrocytes embedded in lacunae. However, this structure does not present detectable calcification, at variance with control cultures maintained in FCS. Accordingly, in the presence of the hormone mixture, the differentiating chondrocytes have low levels of alkaline phosphatase activity. This report indicates that T3 and insulin are primary factors involved in the onset and progression of chondrogenesis, while dexamethasone supports cell viability and modulates some differentiated functions.
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PMID:Thyroid hormone, insulin, and glucocorticoids are sufficient to support chondrocyte differentiation to hypertrophy: a serum-free analysis. 142 44

The effects of tri-iodothyronine (T3) and insulin-like growth factor-I (IGF-I) on [3H]thymidine incorporation, alkaline phosphatase (ALP) activity and IGF-I receptor mRNA levels were studied in rat epiphyseal chondrocytes cultured in monolayer. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in monolayer culture and precultured for 7-14 days in Ham's F-12 medium supplemented with 10% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture the medium was changed to Ham's F-12 medium containing 1% (v/v) serum from hypophysectomized rats, and the effects of T3 and/or IGF-I on DNA synthesis ([3H]thymidine incorporation), ALP activity (a late marker of differentiated epiphyseal chondrocytes) and IGF-I receptor mRNA levels were studied. ALP activity was increased by T3 in a dose-dependent manner with a maximal response at 10 micrograms T3/l (678 +/- 86% compared with control culture). The increase in ALP activity was accompanied by a concomitant decrease in [3H]thymidine incorporation (52 +/- 14% compared with control culture). Human GH (hGH; 50 micrograms/l) and IGF-I (25 micrograms/l) had no stimulatory effect on ALP activity. However IGF-I (10 micrograms/l) exerted an inhibition on the T3 (10 micrograms/l)-induced increase in ALP activity (64 +/- 9% compared with T3-treated culture). T3 (3 micrograms/l) inhibited the increase in [3H]thymidine incorporation caused by 25 micrograms IGF-I/l (51 +/- 13% compared with IGF-I-treated culture). Furthermore, IGF-I receptor mRNA levels were increased by 10 micrograms T3/l (137 +/- 4.2% compared with control culture) while no effect of hGH (50 micrograms/l) or IGF-I (25 micrograms/l) was demonstrated. Both T3 and IGF-I were shown to interact with epiphyseal chondrocytes and both substances seemed to affect cell proliferation and maturation and therefore longitudinal bone growth. Furthermore, the results indicated that IGF-I is important for proliferation of the cells while T3 initiates the terminal differentiation of epiphyseal chondrocytes.
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PMID:Effects of tri-iodothyronine and insulin-like growth factor-I (IGF-I) on alkaline phosphatase activity, [3H]thymidine incorporation and IGF-I receptor mRNA in cultured rat epiphyseal chondrocytes. 143 76

Acromegaly is characterized by growth hormone (GH) hypersecretion and insulin-like growth factor-I (IGF-I) excess, both of which stimulate osteoblast proliferation. At diagnosis, GH excess has usually been present for years. Furthermore, impaired gonadotropin secretion with hypogonadism is frequent. To date, studies of changes in bone mineral density (BMD) in acromegaly have been limited and the available data inconsistent. To investigate the effects of GH excess on proximal femur and lumbar spine BMD, a case series of 25 patients with acromegaly (8 eugonadal, 17 hypogonadal) documented by high plasma GH and IGF-I concentrations was studied. BMD was measured using dual-photon absorptiometry, hormonal and biochemical measurements, which included GH, IGF-I, serum calcium, phosphate, alkaline phosphatase, 1,25 dihydroxy vitamin D and urinary calcium and hydroxyproline excretion. Seven patients were re-studied after IGF-I was suppressed for six months by the somatostatin analog 201-995 (five patients) or pituitary adenomectomy (two patients). BMD was normal in 22 patients and was decreased at one site each in one eugonadal and two hypogonadal patients. BMD was similar between the eugonadal and hypogonadal groups at all sites. Urinary hydroxyproline excretion was equally increased in both groups. There was no correlation between any of the hormonal or biochemical parameters and the age, sex, race and body mass index matched Z-scores of BMD at any site. Following normalization of IGF-I for 6 mo in seven patients, there was no significant change of BMD. We conclude that proximal femoral and lumbar spine BMD is normal in most patients with active acromegaly, including those who are hypogonad. Successful treatment of acromegaly does not result in major short-term changes in BMD.
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PMID:Bone mineral density of the axial skeleton in acromegaly. 151 33

Renal tubular reabsorption of phosphate in response to GH administration was studied in 28 short Japanese children, aged 5-11 yr (height SD score, less than -2.0 SD). Three groups included a classical GH deficiency (group 1; n = 12), a partial GH deficiency (group 2; n = 7), and children with non-GH deficiency (group 3; n = 9), depending on the peak response of serum GH in four provocative tests. Serum phosphorus, alkaline phosphatase, insulin-like growth factor-I (IGF-I), osteocalcin, and ratio of the maximum tubular reabsorption rate for phosphorus to the glomerular filtration rate (Tmp/GFR) were all significantly lower in group 1 compared with findings in groups 2 and 3 (P less than 0.05, P less than 0.01, and P less than 0.001). After the administration of GH (0.1 U/kg.day) for 4 consecutive days, increments in serum phosphorus and Tmp/GFR were significantly higher in group 1 than in group 2 (P less than 0.01 and P less than 0.01) or group 3 (P less than 0.01 and P less than 0.01), whereas the increment in IGF-I was similar in all 3 groups, and the levels of serum alkaline phosphatase and osteocalcin remained unchanged in all 3 groups. The calculated ratio of the increment in Tmp/GFR to the increment in IGF-I (delta Tmp/GFR/delta IGF-I) was highest in group 1, intermediate in group 2, and lowest in group 3 (P less than 0.001). One year after the GH treatment (0.5 U/kg.week), height velocity was 7.9 +/- 2.2 cm/yr in group 1 and 5.9 +/- 1.2 cm/yr in group 2; no child in group 3 was treated. When the above calculated parameters, delta Tmp/GFR/delta IGF-I and increment in height velocity (difference between pre- and posttherapy values), were taken into account, there was a significant positive correlation (n = 19; r = 0.78; P less than 0.001). This parameter can be used for purposes of predicting the outcome after 1 yr of GH therapy.
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PMID:Renal handling of phosphate can predict height velocity during growth hormone therapy for short children. 154 58

Treatment of bovine chromaffin cells with insulin-like growth factor-I (IGF-I) caused the activation of a protein kinase that phosphorylates microtubule-associated protein-2 (MAP-2) in vitro. Activation of MAP-2 kinase by IGF-I varied with the time of treatment (maximal at 10-15 min) and the concentration of IGF-I (maximal at 10 nM). The IGF-I-activated MAP-2 kinase was localized to the soluble fraction of chromaffin cell extracts and required Mg2+ for activity. The IGF-I-activated kinase also phosphorylated myelin basic protein, but had little or no activity toward histones or ribosomal S6 protein. To examine the role of protein tyrosine phosphorylation in the activation of the MAP-2 kinase, we isolated phosphotyrosine (PTyr)-containing proteins from chromaffin cells by immunoaffinity adsorption on anti-PTyr-Sepharose beads. Anti-PTyr-Sepharose eluates from IGF-I-treated cells showed increased MAP-2 kinase activity; thus, the MAP-2 kinase (or a closely associated protein) appears to be a PTyr-containing protein. Treatment of anti-PTyr-Sepharose eluates or crude chromaffin cell extracts with alkaline phosphatase significantly decreased kinase activity toward myelin basic protein, indicating that phosphorylation of the IGF-I-activated kinase is required for its activity.
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PMID:Activation of a microtubule-associated protein-2 kinase by insulin-like growth factor-I in bovine chromaffin cells. 165 24

The possibility that the non-osteogenic mouse pluripotent cell line, C3H10T1/2 (10T1/2), could be induced to differentiate into osteogenic cells by various hormones and cytokines was examined in vitro. Of a number of agents tested, recombinant human bone morphogenetic protein-2 (rhBMP-2) and retinoic acid induced alkaline phosphatase (ALP) activity in 10T1/2 cells. rhBMP-2 also induced mRNA expression of ALP in the cells. Dexamethasone, 1 alpha, 25-dihydroxyvitamin D3, transforming growth factor-beta 1 and insulin-like growth factor-I did not stimulate ALP activity. Treatment with rhBMP-2 greatly induced cAMP production in response to parathyroid hormone in 10T1/2 cells. No ALP activity was induced in NIH3T3 fibroblasts treated with rhBMP-2 or retinoic acid. These results indicate that 10T1/2 cells have a potential to differentiate into osteogenic cells under the control of BMP-2.
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PMID:The non-osteogenic mouse pluripotent cell line, C3H10T1/2, is induced to differentiate into osteoblastic cells by recombinant human bone morphogenetic protein-2. 169 39

Ten intact male Holstein calves averaging 75 kg of BW and 59 d of age were used to study the effects of daily injections of 0 (control) or 10 mg of sometribove (recombinant methionyl bST) for 6 wk on performance, health, carcass composition, N metabolism, chemical blood characteristics, and hormone profiles. Average daily gain, feed intake, feed:gain ratio, and height at withers, hip, and hock were not influenced by bST. Carcasses from bST-treated calves contained 5% more protein and 36% less lipid than controls. Circulating concentrations of Ca, P, glucose, urea N, alkaline phosphatase, creatine phosphokinase, insulin-like growth factor-I, and insulin were not affected by bST. Packed cell volume was decreased about 7% (29.9 vs. 32.4%) in the bST calves. Hormone injection did not adversely affect health of the calves as measured by body temperature and by pulse and respiration rates. The most profound effects of sometribove were a reduction in carcass lipid and an increase in body proteins. These effects may be of some practical importance when leanness of carcass is desirable.
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PMID:Effects of sometribove on performance, carcass composition, and chemical blood characteristics of dairy calves. 175 30

Low-level exposure to lead impairs longitudinal growth in children and in experimental animals. The proposed mechanisms include decreased osteocalcin secretion in response to 1 alpha,25-(OH)2 vitamin D3 and decreased response to insulin-like growth factor-I. The interaction of lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I was investigated in an osteoblast-like cell line from rat osteosarcoma, ROS 17/2.8. Cells were cultured 24 hr in a serum-free medium with lead, 1 alpha,25-(OH)2 vitamin D3, and insulin-like growth factor-I. 1 alpha,25-(OH)2 vitamin D3 (10 nM) evoked a 4-5 X increase in osteocalcin secretion and a 100% increase in cellular alkaline phosphatase activity but no increase in DNA/cell layer. Insulin-like growth factor-I (92.5 ng/ml) evoked a 100% increase of osteocalcin secretion and a 20% increase in cellular DNA contents but no change in cellular alkaline phosphatase activity. Basal and stimulated cellular osteocalcin secretion, cellular alkaline phosphatase activity, and DNA contents were significantly inhibited by addition of 1-10 microM lead. The data are consistent with a toxic effect of lead on osteoblastic function and the cellular responses to 1 alpha,25-(OH)2 vitamin D3 and insulin-like growth factor-I. This interaction may be relevant to impaired childhood growth at low levels of lead exposure.
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PMID:Lead inhibits the basal and stimulated responses of a rat osteoblast-like cell line ROS 17/2.8 to 1 alpha,25-dihydroxyvitamin D3 and IGF-I. 233 May 89

Numerous reports have appeared in the literature indicating phenotypic heterogeneity among cells of the osteoblastic lineage. This diversity may be due to either certain stages of differentiation or a subspecialization of already terminally differentiated osteoblasts. To obtain answers to this question, we report on studies undertaken to clone bone cell populations from 1 day postnatal rat calvaria which express well defined differences in phenotype. To achieve this goal, we have used the soft agarose cloning technique which previously has almost exclusively been applied to clone cells of neoplastic origin. The reason for being able to employ this method is based on the fact that bone cells can be induced by transforming growth factor-beta to reversibly acquire the transformed phenotype, an event expressed by anchorage-dependent bone cells to form progressively growing colonies in soft agarose. Individual colonies, harvested from agarose, were expanded to clonal bone cell populations. Characterizing 48 cell clones by detection of osteoblastic cell markers such as alkaline phosphatase activity, PTH- and prostaglandin-E2-induced adenylate cyclase activity, osteocalcin mRNA synthesis, as well as collagen synthesis, 7 subsets of osteoblastic cell types were identified. Each subset was found to express a distinct phenotype, indicated by the absence or presence of osteoblastic cell markers. Some clones, previously found not to exhibit any osteoblastic traits, developed PTH responsiveness when treated with insulin-like growth factor-I/transforming growth factor-beta, suggesting that these clones may originate from the osteoprogenitor cell pool. While most clonal cell populations were characterized as fully functional osteoblastic cells, some clones expressed merely 1, 2, or 3 osteoblastic markers, which suggests that they may represent stages of differentiation along the osteogenic pathway. In addition, other subclones displayed the capacity to synthesize osteocalcin and showed PTH and prostaglandin-E2 responsiveness, but were found to be devoid of alkaline phosphatase activity. Others expressed all osteoblastic cell markers except PTH responsiveness. The phenotypic constellation of the latter suggests that these cell clones may represent mature osteoblast-like cells, which, perhaps due to environmental circumstances present at the time of isolation, have become altered in accordance with the physiological requirements of the tissue.
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PMID:Evidence for heterogeneity of the osteoblastic phenotype determined with clonal rat bone cells established from transforming growth factor-beta-induced cell colonies grown anchorage independently in semisolid medium. 267 79


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