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1.
Socorro Vargas Roger Bouillon Hugo Van Baelen Dr. Lawrence G. Raisz 《Calcified tissue international》1990,47(3):164-168
Summary Vitamin D and its metabolites are tightly bound to the serum vitamin D-binding protein (DBP) and only the free hormone is
considered to be physiologically active. On the other hand, DBP could interact with cell membranes and even favor its intracellular
entry. The present study was undertaken to examine the effects of DBP on bone resorption stimulated by 1,25-dihydroxyvitamin
D3 [1,25(OH)2D3]. Forelimb bones from 19-day-old fetal rats were cultured for 5 days in the presence of purified human or rat serum albumin
(hSAP or rSAP) and 1,25(OH)2D3, with or without human or rat DBP (hDBP or rDBP). Bone resorption was assessed by measuring the release of previously incorporated45Ca. We found that the resorptive response to 1,25(OH)2D3 was minimally altered by hDBP (5 μM). The minimal effects of hDBP on 1,25(OH)2D3 activity on rat bones might be explained by a 6-fold lower affinity of hDBP (1.1×107 M−1) than rDBP (5.9×107 M−1) for 1,25(OH)2D3 or by species differences in cellular recognition of DBP. In a homologous rat system, however, rDBP at low (0.5 μM) or physiological
(5 μM) concentration significantly decreased 1,25(OH)2D3-induced bone resorption. These data therefore support the hypothesis that free rather than DBP-bound 1,25(OH)2D3 is physiologically important. 相似文献
2.
Sol Epstein M.D. Mark Schlosberg Michael Fallon Steven Thomas Colin Movsowitz Firhaad Ismail 《Calcified tissue international》1990,47(3):152-157
Summary We have previously shown that cyclosporin A (CsA) produces high bone remodeling with resorption exceeding formation and loss
of bone volume in the rat. This may have important clinical implications where CsA is widely used in organ transplantation.
1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is a bone mineralizing hormone which also has immune modifying properties. Consequently, we studied the effect of combined
CsA and 1,25(OH)2D3 administration over 28 days in four groups of rats. Group A received vehicle (n=10), group B CsA (15 mg/kg) (n=10) alone,
group C 1,25(OH)2D3 plus CsA (n=15), and group D 1,25(OH)2D3 alone (20 ng/100 g) (n=15). Rats were bled periodically at day 0, 7, 14, and 28 and Ca, parathyroid hormone (PTH), 1,25(OH)2D, osteocalcin (bone Gla-protein, BGP), BUN, and creatinine were measured. Rats were sacrificed on day 28 and bones were examined
histomorphometrically. Compared to controls, CsA resulted in significant elevation of BGP and a transient increase in 1,25(OH)2D with excess bone remodeling and loss of bone volume. 1,25(OH)2D3 administration produced hypercalcemia, a significant rise in BGP, with suppression of PTH and increased osteoid volume. Combined
therapy prevented the loss of bone volume probably due to increased osteoid tissue and enhanced osteoblast activity. Renal
dysfunction, a side-affect of CsA, was not a factor. In conclusion, 1,25(OH)2D3 combined with CsA restores bone volume which is accompanied by increases in serum calcium and BGP. 相似文献
3.
Dr. M. Gunness-Hey I. Gera J. Fonseca L. G. Raisz J. M. Hock 《Calcified tissue international》1988,43(5):284-288
Summary Parathyroid hormone (PTH) alone is known to increase bone mass, but clinical studies of osteoporotic men suggest that when
1,25 dihydroxyvitamin D3 (1,25(OH)2D3) is given in combination with PTH, the effect on bone growth is enhanced. To determine if 1,25(OH)2D3 alone would stimulate bone growth, young male rats were given daily subcutaneous injections of either vehicle or 2.5, 5,
10, or 20 ng 1,25(OH)2D3 per 100 g body weight for 30 days. To determine if 1,25(OH)2D3 would augment the PTH anabolic response, rats were given daily subcutaneous injections of either vehicle for 12 days; or
4 μg/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)2D3; or 8 μg/100 g hPTH alone or in combination with 5 ng/100 g 1,25(OH)2D3. Calcium (Ca), dry weight (DW), and hydroxyproline (Hyp) of the distal femur; the rate of mineralization in the metaphysis
of the proximal tibia; and serum calcium and phosphate were measured. Low normocalcemic doses of 1,25(OH)2D3 did not significantly stimulate bone growth. 1,25(OH)2D3 did not augment the PTH-stimulated anabolic effect in young male rats. Low doses (2.5 and 5 ng) of 1,25(OH)2D3 were not hypercalcemic, and there was no increase in total bone calcium or dry weight although the 5 ng dose increased trabecular
bone calcium. 1,25(OH)2D3 at 10 and 20 ng increased trabecular bone DW and Hyp, but mineralization was impaired and rats were hypercalcemic. 1,25(OH)2D3 in combination with PTH did not augment the PTH stimulation of bone growth as trabecular and cortical bone Ca, DW, and HYP
were not increased in rats given both hPTH and 1,25(OH)2D3 compared with values for rats treated with hPTH alone. 相似文献
4.
The effects of retinoic acid (RA), and calcitriol are mediated by specific nuclear receptors (RARs and VDR, respectively). Induction of RAR and VDR responsive elements in target genes requires a cofactor, the retinoid-X-receptor (RXR), with its ligand 9-cis RA. We have previously demonstrated the expression of RARs and RXRs in osteoblasts, and herein investigated the effects of the retinoids all-trans RA and 9-cis RA alone and combined with calcitriol on bone resorption in vitro, measured by 45Ca-release from prelabeled neonatal mouse calvarial bones. All-trans RA and 9-cis RA were powerful stimulators of bone resorption and essentially equipotent. At threshold concentrations (1 nM) both 9-cis RA and at-RA markedly inhibited the resorption induced by calcitriol (1 pM). The findings are compatible with a physiological role for retinoids in bone metabolism. 相似文献
5.
Dr. Pierre J. Marie Monique Hott Marie-Thérèse Garba 《Calcified tissue international》1985,37(3):268-275
Summary The purpose of this study was to evaluate whether the 1,25(OH)2D3-induced increased bone mineralization in the mouse occurs in response to stimulation of bone resorption. In order to inhibit
bone resorption, 35-day-old mice were given 16 μmol/kg/day of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (AHPrBP) for
10 days, the first injection occurring 3 days prior to the continuous infusion of 0.06, 0.13, or 0.20 μg/kg/day of 1,25(OH)2D3 for 7 days. Two groups of mice were treated with AHPrBP or 1,25(OH)2D3 alone. The skeletal changes were assessed by histomorphometric study of caudal vertebrae after double3H-proline and double tetracycline labelings for evaluation of the matrix apposition rate (MaAR) and mineral apposition rate
(MiAR), respectively. Treatment with AHPrBP alone or combined to 1,25(OH)2D3 decreased the number of acid phosphatase-stained osteoclasts and reduced the endosteal MaAR and MiAR and the amount of osteoid.
When given alone, 1,25(OH)2D3 increased serum calcium above normal, enhanced the number of histochemically active osteoclasts, and stimulated the endosteal
MiAR. Pretreatment with AHPrBP blocked both the increase in serum calcium and the stimulation of the MiAR induced by 1,25(OH)2D3 infusion though serum 1,25(OH)2D3 levels rose according to the dose given. The results show that 1) the serum calcium and the bone resorbing responses to 1,25(OH)2D3 infusion are prevented by pretreatment with AHPrBP, and 2) the stimulatory effect of 1,25(OH)2D3 on the mineralization rate is blocked when bone resorption is inhibited. The data indicate that 1,25(OH)2D3 promotes bone mineralization in the mouse mainly in response to stimulation of bone resorption. 相似文献
6.
Summary 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) (2.0 μg) was given intramuscularly to 6 healthy adult males. Twenty-four circadian patterns of blood-ionized calcium (Ca2+), serum phosphate (Pi), and total calcium (CaT) were assessed pre- and posthormone administration. Correlations of mean mineral rhythms with normative models were significant
for each mineral pattern on both study days. Mean Ca2+ and CaT rhythms became weakly correlated after hormone treatment (r=.39). A small but statistically significant increment in the
24 h grand mean Ca2+ concentration was observed on the treatment day compared with the baseline day. However, this increment is less than the
year-to-year variability in the grand mean mineral concentrations derived from the same subjects studied under baseline conditions
previously. These data indicate that acute parenteral administration of near-physiological (2.0 μg) doses of 1,25(OH)2D3 appears to have no major effect on circadian mineral pattern shape or mean mineral concentrations. 相似文献
7.
Tony J. Hall William Higgins Chantal Tardif Timothy J. Chambers 《Calcified tissue international》1991,49(5):328-332
Summary We have assessed the effects of five sulfonamides with widely varying inhibitory activity for carbonic anhydrase (CA) in the
bone slice assay using disaggregated rat osteoclasts (OCs), and in the Maren assay where the catalytic activity of purified
CA isozyme II (CA II) was measured. There was an excellent correlation between the relative potencies of the compounds in
the two assays: ethoxzolamide (ETH)>acetazolamide (AZ)>M&B 21659>M&B 9811>M&B 7973. In the bone slice assay, ETH and AZ were
found to be the most potent inhibitors of OC bone resorption, with IC50 values of 0.09 and 0.8 μM, respectively (from plan surface area of bone resorbed). These results support previous observations
showing that OCs use CA II to generate protons during bone resorption and that CA II activity is essential for OCs to be able
to resorb bone. 相似文献
8.
Summary Calvarial bones from hypophosphatemic (Hyp) mice and normal littermates were cultured in a chemically defined medium to determine:
(a) the effect of medium phosphate (Pi) concentration (1, 2, and 3 mM) on collagen synthesis; (b) the effect of 1,25-dihydroxycholecalciferol
[1,25(OH)2D3] (10−12M–10−7M) on collagen synthesis; and (c) whether bone responsiveness to 1,25(OH)2D3 was affected by changes in medium Pi concentration. Bone collagen synthesis was evaluated by measuring [3H]hydroxyproline formation. The distribution of labeled hydroxyproline between bone explant and culture medium (total and
dialyzable fraction) was studied. These experiments confirm that 1,25(OH)2D3 inhibits specifically bone collagen synthesis in vitro. We did not detect any effect of medium Pi concentration on basal
collagen synthesis but were able to demonstrate that lowering medium Pi concentration increased the 1,25(OH)2D3-induced inhibition of collagen synthesis. Bones from both genotypes responded to 1,25(OH)2D3, but modulation of this response by changes in Pi concentration was altered in Hyp bone as, in contrast to normal bone, its
response to 1,25(OH)2D3 was unaffected when medium Pi concentration was decreased from 3 to 2 mM. These findings support the hypothesis of an altered
response of bone to 1,25(OH)2D3 in the Hyp mouse. 相似文献
9.
Summary The effects of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) administration on serum osteocalcin (Oc) concentrations were determined. 2.0 μg doses of 1,25(OH)2D3 were administered orally and intravenously to four healthy adult males. Blood was sampled hourly for 24 hours on four occasions:
once prior to the two treatment days (i.v. and p.o.), on each of the treatment days, and during a second nontreatment day
2 years later. Mean circadian Oc rythms of the four subjects on each study day were compared with each other and with a previously
derived mathematical representation of the normative Oc rhythm, the circadian Oc rhythm model. We found overall conservation
of the mean Oc pattern across time and 1,25(OH)2D3 treatment. However, 1,25(OH)2D3 administration resulted in a rapid rise (within 6 hours) in Oc concentrations that blunted or eliminated the morning fall
in Oc levels. The increased Oc levels were sustained for the remainder of the 24 hour period though pattern shapes converged
with those of the nontreatment days and the model. We conclude that serum Oc levels are rapidly responsive to near physiological
doses of 1,25(OH)2D3 in healthy adult males and that the effects are maintained for at least 24 hours. 相似文献
10.
Summary The direct effect of 1,25(OH)2D3 upon osteoclast formation from precursor cells is still unknown. In the present experiments we have tested the effects of
1,25(OH)2D3 on the generation of osteoclastlike cells in cat bone marrow cultures. These cultures contain proliferating nonattached mononuclear
cells and precursor cells that subsequently attach to the culture flask surface and then fuse to form multinucleated osteoclastlike
cells. After 7 days of culture we separated the nonattached precursor cells from the attached cells and studied the effects
of 1,25(OH)2D3 (10−10 M–10−8 M) on multinucleated cell formation in these two cell populations. In cultures derived from the non-attached precursor cells,
7 days of treatment with 1,25(OH)2D3 (10−8 M) resulted in a 180% increase in the number of attached mononuclear cells and a 90% increase in the number of nuclei contained
within multinucleated cells. These effects were dose-dependent. 1,25(OH)2D3 did not have a consistent effect on the number of nonattached precursor cells. In cultures derived from attached cells, 7
days of treatment with 1,25(OH)2D3 (10−8 M) induced a 50% increase in the number of mononuclear attached cells and a 40% increase in the number of nuclei within polykaryons.
The most likely explanation for these results is that 1,25(OH)2D3 promotes the differentiation and subsequent adhesion of nonattached precursor cells, stimulates proliferation of attached
mononuclear precursor cells, and possibly stimulates fusion of these attached precursor cells. 相似文献
11.
Human parathyroid hormone (1–34) and salmon calcitonin do not reverse impaired mineralization produced by high doses of 1,25 dihydroxyvitamin D3 总被引:2,自引:0,他引:2
M. Gunness-Hey Dr. J. M. Hock I. Gera J. Fonseca J. Poser J. Bevan L. G. Raisz 《Calcified tissue international》1986,38(4):234-238
Summary We have reported recently that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25(OH)2D3) stimulated bone matrix formation but impaired mineralization. The objective of this study was to determine if parathyroid
hormone (hPTH 1-34) or calcitonin (sCT) would mineralize the osteoid induced by 1,25(OH)2D3 in rat long bones. In one experiment, male Sprague-Dawley rats were given daily subcutaneous injections of vehicle: 8 μg
hPTH(1-34); 125 ng 1,25(OH)2D3; or both 8 μg hPTH and 125 ng 1,25(OH)2D3 per 100 g body weight for 12 days. In a second experiment, rats received daily injections of vehicle: 2 U sCT; 125 ng 1,25(OH)2D3; or both 2 U sCT and 125 ng 1,25(OH)2D3 per 100 g body weight for 18 days. Calcium (Ca), hydroxyproline (Hyp), and dry weight (DW) of the distal femur and serum
calcium, phosphate, and serum bone Gla protein (BGP) were measured. In rats given both 1,25(OH)2D3 and hPTH, total bone DW and Hyp increased (P<.01) without a corresponding increase in bone Ca so that Ca/Hyp decreased 47% (P<.01) from control and remained comparable to values for rats treated with 1,25(OH)2D3 alone. In rats treated with both 1,25(OH)2D3 and sCT, total bone DW and Hyp increased while Ca decreased so that Ca/Hyp decreased 38% from control (P<.05), and remained comparable to values for rats treated with 1,25(OH)2D3 alone. These results indicate that hPTH or sCT, given by intermittent injection to rats for 12 or 18 days respectively, failed
to mineralize the osteoid induced by high doses of 1,25(OH)2D3. 相似文献
12.
Dr. Michael Silbermann Klaus von der Mark Nitza Mirsky Marion van Menxel Dina Lewinson 《Calcified tissue international》1987,41(2):95-104
Summary Thein vivo effects of high doses of 1,25(OH)2D3 were studied in condylar cartilage of suckling mice. Seven-day-old animals were treated with 20 ng of the hormone for 7 consecutive
days. Biochemical assays on collagen content and synthesis were complemented by structural studies using light and electron
microscopy. Indirect immunofluorescent methods were used for the localization of type I and II collagens and for fibronectin.
This study revealed that the protein content of the condyle decreased substantially following the administration of the hormone.
Protein synthesis increased in hormone-treated animals during the first 4 days but was significantly inhibited theeafter.
Collagen synthesis, however, was inhibited instantaneously, followed by a decrease in the percentage of cold hydroxyproline
of the total protein. Hormone-treated condyles showed a marked decrease in the distribution of type I collagen, no apparent
change in the distribution of type II collagen, but an enhanced reactivity for fibronectin especially around hypertrophic
chondrocytes. SDS-gel electrophoresis of collagen chains suggested that the hormone did not induce a significant change in
the ratios of type I and II collagen chains, yet additional peaks became evident in 1,25(OH)2D3-treated specimens. The decrease in collagen synthesis was accompanied by ultrastructural changes in the appearance of the
extracellular collagen bundles. They later appeared as a dense meshwork of collagen fibrils, a feature that was lacking in
control tissues. The changes in collagen fibrillogenesis could be explained by ourin vitro studies indicating a marked depression of35S-sulfate incorporation secondary to treatment with 1,25(OH)2D3. The hormone was also found to suppress the incorporation of3H-thymidine, hence it may be concluded that 1,25(OH)2D3, when used in high concentrations, possesses an inhibitory effect upon both the proliferative activity of the cartilage progenitor
cells as well as upon the metabolic activity of the condylar cells as related to collagen and glycosaminoglycans synthesis. 相似文献
13.
Summary To determine the relationship between alkaline phosphatase (AP), 1,25(OD)2D3 and bone formationin vivo, we have examined the effects of levamisole, a stereospecific inhibitor of AP on bone formation and on 1,25(OH)2D3-stimulated bone mineralization in the mouse. Normal mice were injected daily with levamisole at doses of 40 and 80 mg/kg/b.w.
The compound was given alone or in combination with 1,25(OH)2D3 infusion (0.05 μg/kg/d) for 7 days. Treatment with levamisole alone inhibited the serum AP activity (mainly of skeletal origin
in mice) by 18.4 and 61.3% for the low and high dose respectively. No deleterious effect on body growth, tibia length, and
bone cells population was detected. The moderate inhibition of AP activity produced by the lower dose of levamisole alone
(18.4%) or in combination with 1,25(OH)2D3 (37.9%) was associated with a reduced endosteal matrix apposition rate (MaAR) determined by double3H-proline labeling method. This effect was related to a levamisole-induced fall in serum phosphate. Despite the moderate inhibition
of AP activity, the mineral apposition rate (MiAR) determined by the double tetracycline labeling method remained normal.
Moreover, 1,25(OH)2D3 infusion still resulted in increased MiAR which was stimulated to the same extent as in the absence of levamisole. By contrast,
the more severe inhibition of AP activity induced by 80 mg/kg of levamisole alone (61.3%) or in combination with 1,25(OH)2D3 (45.8%) inhibited both the MaAR and the MiAR and prevented the stimulatory effect of 1,25(OH)2D3 on bone mineralization. The data show that AP activity affects the bone matrix and mineral apposition ratesin vivo and that severe inhibition of AP activity inhibits the 1,25(OH)2D3-induced stimulation of bone mineralization in the mouse. 相似文献
14.
J. M. Hock M. Gunness-Hey J. Poser H. Olson N. H. Bell L. G. Raisz 《Calcified tissue international》1986,38(2):79-86
Summary We previously reported that pharmacologic doses of 1,25 dihydroxyvitamin D3 (1,25-(OH)2D3) given for 2–3 days, inhibited osteoblastic collagen synthesis in young rats. In this study, we tested the effects of 5,
25, and 125 ng of 1,25(OH)2D3 injected subcutaneously into 6-week-old rats for 12 or 18 days. In rats given 125 ng, cortical bone of distal half femurs
exhibited decreased calcium (Ca) content but dry weight and hydroxyproline (Hyp) content were no different from control. Trabecular
bone Ca was not different from control but dry weight and Hyp were increased. When cortical and trabecular bone were combined,
there was a decrease in Ca, an increase in Hyp, and a 50% decrease in Ca:Hyp. Fluorescent labels given after 8 days of treatment
were either diffuse or absent in calcified sections from rats given 125 ng, indicating impaired mineralization. The 25 and
125 ng doses produced hypercalcemia with normal serum phosphate. There was a dose-related increase in serum immunoreactive
bone gla protein (BGP) and serum 1,25(OH)2D3 and a decrease in serum 25 (OH)D3. At the 5 ng dose, no adverse effects were seen on body growth. With 25 ng and 125 ng, growth was inhibited. Increased serum
urea nitrogen and histologic evidence of nephrocalcinosis occurred at the 125 ng dose. When 125 ng was given for 12 days and
then withdrawn for 6 days, systemic toxicity decreased and bone Hyp and Ca increased so that Ca:Hyp remained low and comparable
to that of rats treated with 1,25(OH)2D3 continuously We conclude that pharmacologic doses of 1,25(OH)2D3 stimulate trabecular bone matrix formation but produce impairment of mineralization, despite a high Ca×Pi product. 相似文献
15.
Summary Vitamin D-deficient, second generation, rachitic rats showed significant decrease in bone Gla protein (BGP) levels in circulation
and in the skeleton. 1,25 dehydroxyvitamin D3 (1,25 (OH)2D3) exhibited the most potent influence on serum BGP levels in a dose-dependent manner. At a dose 25 ng/100 g body weight 1,25
(OH)2D3 showed a cumulative effect, i.e., the longer the treatment, the more circulating BGP was detected 24,25 dehydroxyvitamin
D3 (24,25(OH)2D3) at the same doses did not show similar effect on the serum BGP levels, regardless of the serum calcium levels. Bone BGP
levels assayed at various sites representing endochondral and intramenbranous ossification demonstrated an opposite pattern.
1,25(OH)2D3 administration was not sufficient to restore bone BGP levels to normalcy, whereas in animals treated with 24,25(OH)2D3 bone BGP and calcium levels were significantly higher than control (Vitamin D3-repleted) levels. The present results can be explained by the dual action of 1,25 (OH)2D3 on both synthesis and release of BGP by bone turnover, whereas 24,25 (OH)2D3 stimulates synthesis and accumulation of BGP in bone. These observations imply that caution is required in the interpretation
of clinical data based solely on serum BGP determination. 相似文献
16.
Summary 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) was recently shown to promote maturation of 5-fluorouracil (5FU)-treated bone marrow cells by up-regulating macrophage-colony stimulating factor (M-CSF) receptors in the presence of interleukin la (IL-1). In order to reveal how 1,25(OH)2D3 interacts with colony-stimulating factors and regulates the differentiation of bone marrow progenitor cell populations, in the present study, natural bone marrow cells were isolated from untreated mice and used in a-minimum essential medium supplemented with 20% heat-inactivated horse serum without added appropriate cytokines. Under the conditions, cells spontaneously differentiated gradually with days of culture, as assessed by expression of macrophage differentiation antigens such as Mac-1 (CD11b) and F4/80. Both M-CSF and granulocyte macrophage-colony stimulating factor (GM-CSF) induced only Mac-1 antigen expression. Simultaneous treatment with M-CSF and 1,25(OH)2D3 enhanced the M-CSF's effect on expression of both antigens, although (1,25(OH)2D3) per se has no effect on the expression for up to 11 days. In addition, successive treatment with 1,25(OH)2D3 and M-CSF or GM-CSF dramatically enhanced expression of both antigens or Mac-1 antigen, respectively. Similarly, both simultaneous and successive treatment with 1,25(OH)2D3 and M-CSF significantly enhanced phagocytic activity and H2O2 production, whereas successive treatment with (1,25(OH)2D3) and GM-CSF significantly enhanced only phagocytic activity. Enzymehistochemical study demonstrated that cells treated simultaneously or successively with 1,25(OH)2D3 and M-CSF were strongly positive for nonspecific esterase (NSE), a macrophage-specific marker, and that simultaneous or successive treatment with 1,25(OH)2D3 and GM-CSF yielded cells strongly positive for NSE or for chloroacetate esterase (ChAE), a granulocyte-specific marker, respectively. These findings suggest that 1,25(OH)2D3 primes bone marrow progenitor cell populations not only to M-CSF but also to GM-CSF and thereby accelerates the CSFs-dependent differentiation of the cells to the macrophage or granulocyte. 相似文献
17.
Norman H. Bell Judith Shary Sheryl Shaw Russell T. Turner 《Calcified tissue international》1985,37(6):588-591
Summary Studies are described in a 53-year-old man with far-advanced pulmonary tuberculosis who developed transient increases in circulating
1,25 dihydroxyvitamin D (1,25(OH)2D) and hypercalcemia while on antituberculous treatment. Serial dilution of an extract of the patient's serum obtained while
he was hypercalcemic displaced [3H]-1,25(OH)2D3 from chick intestinal receptor in a manner identical to authentic 1,25(OH)2D3. Serum 25-hydroxyvitamin D (25OHD) was suppressed during the abnormal elevation of serum 1,25(OH)2D. It is concluded that tuberculosis is another chronic granulomatous disease in which hypercalcemia may result from abnormal
metabolism of vitamin D. 相似文献
18.
Summary Cultured mouse kidney cells grown in serum-free medium were used to assess the metabolism of 25-hydroxyvitamin D3 in the presence of simulated metabolic acidosis. Kidney epithelial cells isolated from 4–6 week old mice were grown to confluence
in a defined serum-free medium at pH 7.4. The confluent monolayers were incubated with tritiated 25-hydroxyvitamin D3 for 6 hours, the samples were extracted, and vitamin D metabolites were separated and quantitated by high pressure liquid
chromatography (HPLC). The pH of the incubation medium was set at 6.9, 7.1, 7.4, or 7.7 by adjusting the bicarbonate concentration,
using chloride as the balancing anion at constant Pco2. When pH was altered at the beginning of the 6 hour assay, production of 1,25-dihydroxyvitamin D3 was the same at each pH. More prolonged pH perturbation for a total of 30 hours likewise had no influence on 1,25-dihydroxyvitamin
D3 production. These results confirm that intact mammalian kidney cells in serum-free culture possess an active 25-hydroxyvitamin
D3-1-hydroxylase and that the activity of the enzyme is unaffected by pH over the range 6.8–7.7. In experiments where acidosis
has been shown to alter 1,25-dihydroxyvitamin D3 production, the mechanism was probably indirect. 相似文献
19.
Y. Seino K. Yamaoka M. Ishida H. Yabuuchi M. Ichikawa H. Ishige H. Yoshino L. V. Avioli 《Calcified tissue international》1982,34(1):265-269
Summary This study presents measurements of serum vitamin D metabolites, calcium and phosphorus as well as measurements of the equilibrium
dissociation constant for duodenal 1,25(OH)2D3 receptor in 15-, 18-, 19-, and 20-day chick embryos in comparison to that in 1- and 118-day-old chicks and to vitamin D-deficient
chicks. The present results showed that: (a) serum 1,25(OH)2D and 24,25(OH)2D levels rise from 15 and 18 to days 19 and 20 of embryonic development while serum phosphate levels are stable; (b) serum
calcium levels rise at hatching to adult levels; (c) the duodenal 1,25(OH)2D3 receptor is detectable in 15-day-old embryo and has a Kd similar to that of 118-day-old vitamin D-replete chicks; and (d)
the activity of 1,25(OH)2D3 receptor in chick duodenal cytosol is maximal at hatching. 相似文献
20.
I. Holt M. W. J. Davie I. P. Braidman M. J. Marshall 《Calcified tissue international》1994,55(2):114-119
The cytokine interleukin-6 (IL-6) was produced by neonatal mouse parietal bones during a 6- or 48-hour culture period in response to prostaglandin E2 (PGE2) and bovine parathyroid hormone (PTH) 1-34 fragment but not 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. At the same time there was an increase in tartrate-resistant, acid phosphatasepositive osteoclasts (TRAP+OC) with all three osteotropic effectors over 6 hours, and an increase in 45Ca release over 48 hours. TRAP+OC numbers on PGE2-stimulated bones were positively correlated with IL-6 concentration. Our aim was to determine if IL-6 mediated this response. Recombinant human IL-6 (rhIL-6) was added to parietal bones in culture at concentrations within the range that PGE2 or PTH would produce during incubation. However, over 6 or 48 hours, rhIL-6 did not stimulate TRAP+OC to increase in number nor did it cause an increase in calcium release over 48 hours. Adding an antibody against mouse IL-6 to bone cultures stimulated with PTH or PGE2 neutralized the resulting IL-6 bioactivity by up to 92% but did not inhibit TRAP+OC formation. We conclude that although IL-6 is produced in response to two important stimulators of bone resorption, it does not mediate osteoclast differentiation or bone resorption in this model.Part of this work has been presented as an abstract to the Bone and Tooth Society Winter Meeting on 6/12/93 at The Royal College of Obstetricians and Gynaecologists, London. 相似文献