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)

This study used a cross-sectional design to investigate relationships among serum insulin-like growth factor (IGF) parameters (total serum IGF-I, IGF-II, and IGF-binding protein-3), serum estradiol, and bone mineral density (BMD) stratified for potential confounders, and a longitudinal design to investigate the effects of hormonal replacement therapy (HRT) on IGFs and BMD. Five hundred and ninety-five perimenopausal women (median age, 50.0 yr; range, 45-56 yr) participating in the Danish Osteoporosis Prevention Study were investigated in a cross-sectional study, and a randomly selected subgroup of 110 was followed after 5 yr in a longitudinal study for changes in serum IGFs and BMD of lumbar spine, femoral neck, and ultradistal forearm during (n = 46) or without HRT (n = 64). In the cross-sectional study, serum IGF-I correlated positively to distal forearm BMD and spine BMD, but not to femoral neck BMD, after stratification for age, body mass index, and other variables. In the follow-up study, HRT decreased IGF-I and IGF-II, but did not influence the age-related decline in IGF-binding protein-3 significantly. Serum alkaline phosphatase and urinary hydroxyproline/creatinine ratio both decreased during HRT, whereas BMD increased compared to control values. After adjustment for age, body mass index, treatment, and other factors, IGF-I correlated positively to changes in forearm and femoral neck BMD, but not to changes in spine BMD. We conclude that serum IGF-I was positively associated to bone mineral density. Oral HRT decreases IGF-I and IGF-II.
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PMID:Effect of sex hormone replacement on the insulin-like growth factor system and bone mineral: a cross-sectional and longitudinal study in 595 perimenopausal women participating in the Danish Osteoporosis Prevention Study. 1040 91

Children with acute lymphoblastic leukaemia (ALL) have reduced bone turnover caused by the disease itself and early intensive chemotherapy, but the effects of later chemotherapy using different drug combinations are uncertain. We report here a longitudinal study on 9 children with ALL randomised to receive an additional third intensification block of chemotherapy, compared with 9 children receiving continuing chemotherapy over the same period. During third intensification, bone alkaline phosphatase, procollagen type I C-terminal propeptide, the carboxyterminal propeptide of type I collagen, procollagen type III N-terminal propeptide and lower leg length all decreased in response to dexamethasone, then returned to (but not beyond) baseline levels after dexamethasone was stopped and other drugs started. These changes were unrelated to circulating insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3 or IGFBP-2. In all children, bone alkaline phosphatase remained below the population mean throughout. We conclude that dexamethasone decreased bone and soft tissue turnover, probably through direct effects on target tissues. The postdexamethasone phase of third intensification and continuing chemotherapy had no major deleterious effect on collagen turnover, but there was evidence of continuing suboptimal bone mineralisation.
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PMID:Effects of a third intensification block of chemotherapy on bone and collagen turnover, insulin-like growth factor I, its binding proteins and short-term growth in children with acute lymphoblastic leukaemia. 1053 79

Ipriflavone (IP), a synthetic isoflavone has been reported to prevent bone loss in both postmenopausal women and ovariectomized (ovx) rats. The purpose of this study was to compare and contrast some of the bone protective mechanisms of IP to those of 17beta-estradiol (E(2)) in ovarian hormone deficiency. Forty-eight 95-day-old Sprague-Dawley rats were assigned to four groups: sham, ovx, ovx+IP, and ovx+E(2). The doses of IP and E(2) were 100 mg and 10 microg/kg body weight per day, respectively. Rats were fed a diet that contained 0.4% calcium, 0.3% phosphorus, and 0.195 nmol vitamin D(3)/g diet. After sacrifice, left femoral bone densities were measured and bone histomorphometry was performed on the proximal tibial metaphysis. Ipriflavone as well as E(2) treatment completely prevented the ovx-induced femoral bone density loss. However, in contrast to E(2), IP did not lower the ovx-induced rise in serum alkaline phosphatase (ALP) activity or insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 concentrations. On histomorphometry analysis, the ovariectomy-induced increase (P < 0. 09) in bone formation rate (BFR) was significantly (P < 0.05) suppressed by E(2) treatment, whereas this higher BFR was maintained in IP-treated animals. These findings indicate that IP is effective in preventing the ovx-associated bone loss. The bone protective mechanisms of IP in ovarian hormone deficiency may be different from those of E(2) and may involve increased rates of bone formation.
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PMID:The synthetic phytoestrogen, ipriflavone, and estrogen prevent bone loss by different mechanisms. 1060 47

Both a decrease in bone formation and an increase in bone resorption have been implicated in the pathogenesis of age-related (type II) femoral neck osteoporosis. While the increase in the bone resorption rate has been shown to be partially related to secondary hyperparathyroidism, the mechanisms underlying the decline in bone formation have not yet been identified. The aim of the present study was to test the hypothesis that the bone formation deficit associated with type II osteoporosis might be due to secondary hyperparathyroidism and/or to a deficiency of the insulin-like growth factor (IGF) system. Circulating concentrations of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-4, IGFBP-5, 25-hydroxycholecalciferol (25(OH)D3), and intact parathyroid hormone (PTH) were measured in 50 elderly women after sustaining a hip fracture and in 50 healthy age-matched controls. In addition, serum levels of osteocalcin (OC), skeletal alkaline phosphatase, and N-terminal procollagen peptide and urinary pyridinium cross-links were determined as markers of bone remodeling, and bone mineral density (BMD) was assessed at the proximal femur. In the patient group, serum was drawn within 18 h of the fracture and prior to surgery. Circulating protein concentrations did not change over this time frame. No difference was found between mean IGFBP-4 serum levels in the two groups studied, while mean levels of IGF-I, IGF-II, IGFBP-3, IGFBP-5, 25(OH)D3, and markers of bone formation were significantly lower (p < 0.006) in patients as compared with healthy subjects. Serum PTH and urinary pyridinium cross-links, however, were markedly increased (p < 0.001) in the osteoporotic group. In pooled data from the normal and osteoporotic populations, age-adjusted multiple regression models based on IGF-I, IGF-II, IGFBP-3, and IGFBP-5 were found to be highly predictive of serum OC (R2 = 19%, p < 0.001) and BMD of femoral neck (R2 = 49%, p < 0.0001), consistent with an effect of the anabolic IGF components on overall bone formation rate. Similar models based on 25(OH)D3 and PTH, however, were statistically unrelated to OC. To address further the potential impact of trauma on circulating IGF system components, we measured IGF system component levels in 10 male patients within 18 h following tibial fracture and in 10 age-matched normal male subjects. There was no significant difference in serum level of any of the IGF system components between the two groups. Although limited by its cross-sectional design, the present study suggests that, in addition to bone resorption resulting from secondary hyperparathyroidism, impaired bone formation associated with deficiency of the IGF system might predispose elderly women to fragility fracture of the proximal femur.
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PMID:Down-regulation of the serum stimulatory components of the insulin-like growth factor (IGF) system (IGF-I, IGF-II, IGF binding protein [BP]-3, and IGFBP-5) in age-related (type II) femoral neck osteoporosis. 1062 75

The current studies were intended to determine whether the anabolic effects of calcitonin (CT) on human osteoblast-line cells were (1) unique to osteosarcoma cells or also evident in osteoblast-line cells derived from normal human bone; and/or (2) associated with effects on several insulin-like growth factor (IGF) system components. Preliminary studies identified several osteoblastic cell lines, derived from normal human bone, which showed calcitonindependent increases in cell proliferation, alkaline phosphatase activity, and/or (45)Ca uptake (P < 0.05-P < 0.001). Two of these cell lines-(human vertebrae) HBV-155 and HBV-163-were included with the human osteosarcoma cell line, SaOS-2, in most of our subsequent studies of calcitonin effects on selected IGF system components: IGF-II, IGF-I, and IGF binding proteins -3, -4, and -5. The results of those studies revealed that a 48 hour exposure to salmon CT caused a dose-dependent (0.03-3 mU/ml) increase in the net extracellular level of IGF-II (r = 0.96, P < 0.01) in serum-free cultures of SaOS-2 cells, with a maximal 60% increase at the highest tested dose (P < 0.02). Similar effects were seen with HBV-163 cells (r = 0.90, P < 0.01) and HBV-155 cells (r = 0.55, P < 0.02). The effect of calcitonin on the extracellular level of IGF-II was biphasic with respect to time: it decreased at 6 hours (P < 0.005 and P < 0.001, for SaOS-2 cells and HBV-163 cells, respectively) and increased at 24 hours (P < 0.02 and P < 0.05). These calcitonin-dependent increases in the extracellular level of IGF-II were associated with parallel increases in IGF-I (P < 0.005 for SaOS-2 cells and P < 0.03 for HBV-163 cells), but calcitonin did not affect the extracellular level of transforming growth factor (TGF)-beta. The calcitonin-dependent changes in IGF-II were not associated with changes in the extracellular levels of IGF binding proteins -3, -4, or -5. Finally, our studies showed that two other members of the CT superfamily-CT gene-related peptide and amylin-did not mimic the effect of CT to increase the extracellular level of IGF-II. Together, these data demonstrate that human osteoblast-line cells derived from normal human bone can respond to CT, and that those responses can include CT dose- and time-dependent increases in the extracellular levels of IGF-I and IGF-II.</hea
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PMID:Calcitonin increases the concentration of insulin-like growth factors in serum-free cultures of human osteoblast-line cells. 1095 80

Children treated for acute lymphoblastic leukemia may develop reduced bone mineral density during treatment, but there is little information on the mechanisms involved. In a prospective, longitudinal study on 15 children with ALL, we undertook serial measurements of markers of bone and collagen turnover, insulin-like growth factor (IGF)-I and its binding proteins (IGFBPs)-3 and -2 during the second year of continuing chemotherapy. In eight patients we also measured lower leg length by knemometry. Height SD scores, lower leg length velocity, IGF-I, and markers of bone collagen turnover did not differ significantly from healthy children. However, bone alkaline phosphatase, a marker of the differentiated osteoblast, was lower (mean SD score, -0.64; p < 0.0001), whereas procollagen type III N-terminal propeptide (P3NP, a marker of soft tissue collagen turnover; mean SD score, +0.93, p < 0.05), IGFBP-3 (mean SD score, +0.76; p < 0.01), and IGFBP-2 (mean SD score, +1.24, p = 0.01) were all higher than in healthy children. IGFBP-3 decreased during episodes of afebrile neutropenia (p < 0.05). Within 3 mo after completion of treatment, bone ALP increased in all eight patients, but collagen markers showed little change. IGFBP-2 returned to normal posttreatment, but P3NP and IGFBP-3 remained significantly elevated compared with healthy children (mean SD scores, +1.51 and +1.36, respectively; p < 0.01). We conclude that continuing chemotherapy was associated with normal growth and bone collagen turnover but enhanced soft tissue collagen turnover. Bone bone alkaline phosphatase was low throughout treatment, which suggests impaired osteoblast differentiation resulting from a direct effect of chemotherapy on bone. Although the effect was reversible, the long-term implications for bone health in survivors remain uncertain.
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PMID:Bone turnover and growth during and after continuing chemotherapy in children with acute lymphoblastic leukemia. 1100 40

The purpose of this study was to compare the insulin-like growth factor-1 (IGF-1) levels and the growth hormone (GH) levels in osteoporotic and non-osteoporotic postmenopausal women. Eleven non-osteoporotic postmenopausal women and 9 women with untreated postmenopausal osteoporosis were included in the study. Bone mineral density (BMD) was assessed by dual energy X-ray absorbtiometry. Serum was assayed for calcium, phosphorus, alkaline phosphatase, bone-specific alkaline phosphatase, parathyroid hormone, IGF-1 and GH levels. IGF-1 levels were 98.8 +/- 43.5 ng/ml for osteoporotic women and 169.8 +/- 50.3 ng/ml for the women with normal BMD (p < 0.05). GH levels were 1.3 +/- 1.1 ng/ml and 1.3 +/- 1.0 ng/ml, respectively. When compared with normal postmenopausal women, IGF-1 levels were found to be lower in women with osteoporosis. IGF-1 seems to play an important role in the development of low bone mass and the present results suggest that IGF-1 is a useful predictor of the presence of osteoporosis.
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PMID:Comparison of serum insulin-like growth factor-1 and growth hormone levels in osteoporotic and non-osteoporotic postmenopausal women. 1106 88

Osteoarthritis is a degenerative joint disease characterized by destruction of the articular cartilage in aging and senescence. The aim of this study was to study the possible treatment of this disease by intraarticular injection of growth factors to osteoarthritic joints of aged animals. 20-month-old female ICR mice were injected with insulin-like growth factor (IGF-1), transforming growth factor-beta (TGF-beta) or TGF-beta+IGF-1 on days 1, 4, and 7. On day 9 the joints were dissected and cultured in the presence of 35S-sulfate and 3H-thymidine. Combined treatment of TGF-beta and IGF-1 resulted in elevated 3H-thymidine incorporation and DNA and protein contents, reduction of 35S-sulfate incorporation and alkaline phosphatase activity, with no significant change in the activity of acid phosphatase. Following injections of TGF-beta, contents of DNA and protein, and incorporations of 3H-thymidine were induced, and 35S-sulfate and alkaline phosphatase activity were reduced. Treatment with IGF-1 resulted in reduced incorporation of 3H-thymidine with no significant changes in the activity of acid phosphatase. Atypically hypertrophic chondrocytes were observed along the articular surface and the endogenous production of TGF-beta and of IGF-1, as revealed by immunohistochemistry, was reduced. It is concluded that although 3H-thymidine incorporation and alkaline phosphatase activity appeared to be induced by TGF-beta and IGF-1, the overall responsiveness of cartilage from aged mice to these growth factors appeared to be inhibitory. Moreover, their effects appeared to be limited to specific cell populations in the cartilage itself.
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PMID:Differential metabolic responses to local administration of TGF-beta and IGF-1 in temporomandibular joint cartilage of aged mice. 1109 Sep 10

In the present study, we test the hypothesis that the stimulation of osteoprogenitor differentiation by the glucocorticoid dexamethasone (Dex) is mediated, at least in part, through components of the insulin-like growth factor (IGF) system. Because it has been suggested that osteoprogenitors and adipocyte progenitors originate from the same precursor cells, and that their differentiation in many systems is reciprocally regulated, the effects of Dex and IGF on adipocyte formation were also evaluated in the same cultures. In view of the presence of IGFs and their binding proteins in serum, we also evaluated to what degree the effects of IGF-1 and IGF-2 on differentiation of osteoblasts and adipocytes were affected by the serum concentration of the culture media. Bone cell populations were isolated from vertebrae of 3-month-old female Wistar rats using an explant culture technique. Osteoprogenitor differentiation was evaluated by a colony assay: Bone-forming osteoblastic colonies (bone nodules) derived from single osteoprogenitors were identified by alkaline phosphatase (ALP) staining and/or staining for mineralized matrix according to the von Kossa technique. Unmineralized nodules and osteoblastic colonies were subsequently identified by their distinctive color and morphology after methylene blue counterstaining. Differentiated adipocytes were identified by Sudan IV staining. IGF-1 and IGF-2 stimulated both osteoprogenitor and adipocyte progenitor differentiation in a dose-dependent pattern. The stimulation of osteoprogenitor differentiation by IGF was not dependent on Dex, but differentiation of adipocytes was. The stimulatory effects of IGF-1 and IGF-2 on osteoprogenitor differentiation were greater in media containing 2.5% fetal bovine serum (FBS) than in media containing 5% or 10% FBS, whereas stimulation of adipocyte formation was greater in media containing 10% FBS. Neutralizing antibody against the type 1 IGF receptor (IGF-1R) partially blocked IGF- and Dex-induced osteoprogenitor differentiation, but did not affect IGF-induced adipocyte formation. This suggests that IGF-stimulated osteoprogenitor differentiation is mediated through IGF-1R, that the stimulation of adipocyte formation by IGF is not, that the stimulatory effects of Dex on osteoprogenitor differentiation are partially mediated through IGF-1R, and that the effects on adipocyte differentiation appear to be mediated through signaling pathways other than the IGF-1R.
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PMID:Insulin-like growth factor-1 and -2 stimulate osteoprogenitor proliferation and differentiation and adipocyte formation in cell populations derived from adult rat bone. 1111 89

This study examines the influence of circulating insulin-like growth factor-1 (IGF-1) and serum leptin on bone mass as well as modulation of bone mass during skeletal development. Moreover, an inverse relationship between IGF-1 and leptin is reported. To evaluate the effects of serum IGF-1 and serum leptin on bone mass in healthy postmenopausal women, and the possible role of IGF-1 in leptin production, we studied a population of 123 women, aged 39-82 years. Bone mineral density (BMD) was determined by whole-body dual-energy X ray absorptiometry, which also enables measurement of body composition. Bone metabolism was assessed by measuring serum total alkaline phosphatase (TAP) and urinary hydroxyproline/creatinine (HP/Cr) excretion. IGF-1 correlated significantly with age (r = -0.28, p < 0.01) and years since menopause (r = -0.24, p < 0.01). A negative correlation was also found with weight and body mass index (r = -0.15, p < 0.05 and r = -0.19, p < 0.05, respectively). Leptin values were strongly correlated with weight (r = 0.7, p < 0.01), BMI (r = 0.7, p < 0.01), fat mass (r = 0.77, p < 0.01), and lean mass (r = 0.39, p < 0.01); a significant correlation was found with total body BMD (r = 0.29, p < 0.01), TAP (r = 0.15, p < 0.05), and HP/Cr (r = 0.18, p < 0.05). After adjustment for BMI, the significance of these relationships disappeared, demonstrating the lack of effect of serum leptin on BMD and bone turnover independent of body weight. On the other hand, the relationship between BMD and fat mass remained statistically significant after adjusting for serum leptin (r = 0.15, p < 0.05). Controlling for BMI eliminated the significant inverse correlation between IGF-1 and leptin; significant differences in leptin levels were found among women in the lower and higher quartile of IGF-1, suggesting that leptin production may be inhibited only at high values of serum IGF-1. We conclude that serum IGF-1 and serum leptin have no direct effect on bone mass and bone turnover.
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PMID:Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women. 1116 51


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