摘要:

AbstractInositol‐containing phospholipids are believed to be intimately involved in the first steps of cellular signalling by certain hormones and neurotransmitters. We examined whether parathyroid hormone (PTH) and calcitonin (CT), two hormones that affect bone physiology, would elicit changes in inositol‐phospholipid metabolism in cultured bone. [3H]inositol readily entered into the tissue phospholipid pool in fetal rat limb bones, and incorporated into phosphatidylinositol (92.9%), phosphatidylinositol‐4‐P (4.5%), and phosphatidylinositol‐4,5‐P2(2.6%). PTH enhanced the incorporation of inositol into PtdIns in limb bones following 2‐ or 24‐h hormone treatments. The effect of PTH was dose dependent (EC50of 0.3–0.4 nM) and occurred in a concentration range similar to that for hormone‐stimulated bone resorption. In contrast, 24‐h treatment with CT‐inhibited inositol incorporation, also in a dose‐dependent manner. Two‐hour CT treatment had variable effects on labeling. CT inhibited the stimulatory effect of PTH at both 2 and 24 h. The effects induced by PTH and CT were specific for PtdIns and were independent of the [3H]inositol pool size. These results indicate that inositol‐phospholipid turnover can be modified during the action of these hormones on bone tissue. Although the time course of hormone‐stimulated inositol incorporation observed here is slower than that found in other tissues, the change in phosphatidylinositol metabolism could mediate delayed effects of PTH or CT. Alternatively, alterations induced by PTH and CT in bone cell membranes, cell populations, or in the mineralized matrix could conceivably result in secondary changes in

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010202

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractAs compared to nonobese white men and women, age‐matched nonobese black subjects and obese white individuals show alterations in the vitamin D–endocrine system that are characterized by increases in mean serum immunoreactive parathyroid hormone (PTH), serum 1,25‐dihydroxyvitamin D [1,25‐(OH)2D], and urinary cyclic adenosine 3,5‐monophosphate (cAMP) and by decreases in mean serum 25‐hydroxyvitamin D (25 OHD) and in urinary calcium. Thus, both groups show secondary hyperparathyroidism which is associated with increased renal tubular reabsorption of calcium and increased renal synthesis of 1,25‐(OH)2D. In view of these findings, studies were conducted in 10 obese black subjects (3 men and 7 women) and in 12 nonobese black individuals (7 men and 5 women), ranging in age from 20 to 35 yr, to determine whether obesity influences the vitamin D–endocrine system in blacks. Body weight averaged 99 ± 4 kg in the obese and 73 ± 3 kg in the nonobese subjects (p<.001). All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, 110 meq of sodium, 65 meq of potassium, and 18 meq of magnesium. Whereas mean serum Gla protein was significantly higher in the obese than in the nonobese black subjects (23 ± 4 vs. 14 ± 2 ng/ml,p<.05), mean serum total calcium, ionized calcium, phosphorus, magnesium, immunoreactive PTH by two different radioimmunoassays (399 ± 23 vs. 312 ± 26 pg/ml and 357 ± 26 vs. 392 ± 27 pg/ml), 25 OHD (5 ± 1 vs. 6 ± 1 ng/ml) and 1,25(OH)2D (43 ± 3 vs. 41 ± 3 pg/ml) were the same in the two groups. Also, mean urinary calcium (105 ± 13 vs. 101 ± 14 mg/d), phosphorus, sodium, potassium, magnesium and cAMP (3.12 ± 0.24 vs. 3.11 ± 0.47 nM/dl GF) and creatinine clearance were the same in the obese and nonobese black men and women. The results indicate that obesity does not produce alterations in the vitamin D–endocrine system that are over and above the changes presen

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010203

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractIn order to differentiate the relative effects of age and estrogen on rates of calcium absorption and serum levels of parathyroid hormone and calcitonin, the effect of oophorectomy with and without estrogen replacement (2 weeks) was studied in rats for 30‐ or 120‐day periods. Whereas oophorectomy for 30 days resulted in a significant decrease in serum calcium and an increase in serum phosphate, no change in either calcium or phosphate was observed in the 120‐day oophorectomized animals. iPTH decreased in both the 30‐ and 120‐day oophorectomized animals although these changes were not significant at the .05 level. Whereas no significant change in basal circulating calcitonin occurred in the 30‐day oophorectomized rats, it decreased significantly in the older animals following the ablative procedure. Forty‐five days following estrogen deprivation, calcitonin release to a calcium secretagogue was significantly blunted. Intestinal calcium absorption decreased with age, and unlike the increments in calcium absorption observed in the younger estrogen‐repleted, 30‐day oophorectomized rat, no change in calcium absorption was observed when estrogens were administered to the older, 120‐day oophorectomized rat. The accumulated data suggest that the effects of estrogen loss on the hormonal control of bone metabolism and calcium absorption are age dependent, and that estrogen contributes significantly to changes in calcium homeostasis observed

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010204

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractUnweighting the hindlimbs of a rat by tail suspension leads to a decrease in bone in the unweighted hindlimbs, but not in the normally weighted forelimbs. We evaluated whether increments in dietary calcium could prevent this. Growing rats were fed diets ranging in calcium content from 0.1% to 2.4%. After the rats were suspended for two weeks, we found no differences between suspended and control animals fed the same diet with respect to calcium transport or serum levels of calcium, phosphorus, 1,25‐dihydroxyvitamin D, and parathyroid hormone. In both groups, increasing dietary calcium reduced active intestinal calcium transport and serum 1,25‐dihydroxyvitamin D levels. The calcium content of the tibia and lumbar vertebra (but not the humerus) was reduced in suspended rats compared to control rats fed the same diet. However, increasing dietary calcium increased the calcium content of all bones in both suspended and control animals. The bone formation rate at the tibiofibular junction (measured by double‐label tetracycline) was reduced in the suspended animals compared to controls and was not altered by dietary calcium. However, the marrow area of the tibia, an indication of bone resorption, did not differ between suspended and control animals and was equally reduced in both groups when dietary calcium was increased. Our data suggest that the deleterious effects of skeletal unweighting on bone formation cannot be explained by changes in the calciotropic hormones and are not reversed by increments in dietary calcium. However, increasing dietary calcium can increase bone calcium, even in unweighted limbs, by decreasing bone resor

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010205

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractCalcitonin deficiency was produced in lactating and age‐matched nonmated rats by thyroidectomy (TX) after transplantation of the parathyroid glands to a thigh muscle. At the end of lactation and a comparable period in the nonlactating rats, this condition resulted in femurs, vertebrae, and tibiae that weighed less than those in the thyroid‐intact controls. Furthermore, the femurs of the CT‐deficient rats were narrower at midshaft and shorter, indicating reduced bone growth. The reduction in bone mass in CT‐deficient rats, although highly significant, was much smaller than that caused by lactation.Adequate thyroid hormone replacement therapy was provided by giving all the TX rats L‐thyroxine (T4) sc or in the drinking water. The body weights of the lactating rats were heavier than those of their nonmated controls but TX had no significant effect on the mean body weight of either group. The previously observed lower concentration of serum calcium in lactating rats than in nonlactating thyroid‐intact rats was also seen in TX rats, indicating that CT is not responsible for the relatively low serum calcium during lactation.Our results showing that the bones of TX rats (with T4replacement) were smaller and lighter than those from thyroid‐intact controls whether lactating or not do not support the concept that CT has a special physiological function to protect the skeleton dur

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010206

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractThe fetal long bone culture system developed by Raisz for the assessment of bone resorption was modified to improve the sensitivity, by using radii and ulnae separately, based on the observation of the consistently higher release of45Ca from the radii than ulnae. Effects of ipriflavone (TC‐80), an isoflavonoid derivative currently under clinical trial for its effect on osteoporosis, on bone resorption were examined in this new system. Ipriflavone and its metabolites (5 out of 6) at 10 μg/ml or more inhibited basal45Ca release from bones. The inhibitory effects were still demonstrated in the presence of submaximal concentration of parathyroid hormone (12.5 ng/ml). The effect of ipriflavone on bone resorption was apparently not due to its toxicity on bone cells, since the inhibition was reversib

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010207

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractThis study compares the metabolism of [14C]‐arachidonic acid between PGE2synthesizing (ROS 17/2.8) and nonsynthesizing (ROS 25/1) osteosarcoma cell lines. In both cell lines: (a) 90% of [14C]‐arachidonic acid was taken up at 24 h. (b) More than 90% of the label was associated with phospholipids. (c) [14C]‐arachidonic acid was rapidly taken up by phosphatidylcholine which reached the highest specific activity around 5 h while the labeling of other phospholipids was still increasing at 24 h. (d) Twenty‐four hours after addition of [14C]‐arachidonic acid only 4% of the label was associated with triacylglycerols in ROS 25/1 and 0.3% in ROS 17/2.8 cells. The calcium ionophore A23187 enhanced the release of [14C]‐arachidonic acid from phospholipids in the PGE synthesizing osteoblastic cells (ROS 17/2.8 and 2/3) but had no effect in nonosteoblastic cells (ROS 24/1 and 25/1). ROS 17/2.8 and 2/3 cells converted the released arachidonic acid as well as exogeneously added arachidonic acid into PGE2. PGE2synthesis depended on arachidonic acid concentration.Among bone resorbing agents, parathyroid hormone and 1,25(OH)2D3had no effect on PGE synthesis, whereas thrombin and rabbit serum stimulated PGE2production. The effect of rabbit serum was abolished by heat inactivation.The findings of this study indicate that the difference in PGE production between the osteoblastic and nonosteoblastic osteosarcoma cells are due mainly to differences in arachidonic acid convers

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010208

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractA 35‐year‐old white male with rheumatoid arthritis who had developed hypercalcemia, hypercalciuria, and nephrolithiasis was found to be abnormally sensitive to vitamin D as a result of lack of regulation of circulating 1,25‐dihydroxyvitamin D (1,25‐(OH)2D). An increase in daily intake of vitamin D from 10 μg (400 units) per day to 50 μg (2000 units) per day produced an abnormal elevation in serum 1,25‐(OH)2D, hypercalcemia, and hypercalciuria which were corrected by prednisone. Serum 25‐hydroxyvitamin D initially was abnormally low, and increased with vitamin D to values which were in the low normal range. There were significant positive correlations between serum 1,25‐(OH)2D (p<.05) and serum calcium and between serum 1,25‐(OH)2D and urinary calcium (p<.05). Serum immunoreactive parathyroid hormone, initially in the lower range of normal, decreased further during hypercalcemia. A radiograph of the chest, gallium scan, and serum angiotensin‐converting enzyme activity were normal. No granulomas or evidence of lymphoma were found in biopsies of the liver and of several lymph nodes. It is concluded that the abnormal calcium metabolism in this patient resulted from increased circulating 1,25‐(OH)2D and that the defect in vitamin D metabolism was not related to sarcoidosis, other granulomatous disease, Hodgkin's disease, or lymphoma. The relationship, if any, of the abnormal metabolism of vitamin D and calcium to rheumatoid arthritis rema

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010209

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractSeveral studies have suggested that the osteoclast is derived from a mononuclear precursor which is found in bone marrow. We have developed a system for studying the formation of osteoclast‐like multinucleated cells in long‐term bone marrow culture of baboon cells. Recombinant human CSF‐GM and highly purified CSF‐1, both of which stimulate the proliferation of monocyte/macrophage precursors, were found to increase the number of osteoclast‐like cells formed in long‐term bone marrow culture. CSF‐GM stimulated multinucleated cell formation more consistently than CSF‐1. The subsequent addition of 1,25‐dihydroxyvitamin D3(1,25‐(OH)2D3) to cultures initially treated with CSF‐GM or CSF‐1 further increased multinucleated cell formation. Autoradiographic studies indicate that CSF stimulated multinucleated cell formation by increasing the proliferation of the precursor cell, and that the potentiating effect of 1,25‐(OH)2D3was caused by fusion of the increased numbers of precursors. These studies suggest that the interaction of locally produced colony‐stimulating factors with circulating calcium regulating hormones may be important in the control of osteoclast fo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010210

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY

摘要:

AbstractWe have reported that 1‐α,25‐dihydroxyvitamin D3[1‐α,25‐(OH)2D3] directly induces fusion of mouse alveolar macrophages at a very high rate (circa 70–80%) by a mechanism involving protein synthesis (Proc. Natl. Acad. Sci. USA 80:5583, 1983; FEBS Letters 174:61, 1984). While examining further the mechanism of the 1‐α,25‐(OH)2D3‐induced fusion of macrophages, we found that polyamines are involved in this mechanism. Mouse alveolar macrophages incubated with 12 nM1‐α,25‐(OH)2D3began to fuse at 36 h and the fusion rate increased linearly up to 60 h. Addition of as much as 0.05–5 mMα‐difluoromethylornithine (α‐DFMO), a specific inhibitor of ornithine decarboxylase, did not inhibit fusion appreciably, but addition of 0.05–5μMmethylglyoxal bis(guanylhydrazone) (MGBG), an inhibitor of S‐adenosylmethionine decarboxylase, strikingly inhibited fusion. When macrophages were treated with both 12 nM1‐α,25‐(OH)2D3and 5μMMGBG for the first 12 h and incubated further for 60 h in fresh medium containing 1‐α,25‐(OH)2D3, fusion was significantly inhibited, suggesting that the 1‐α,25‐(OH)2D3‐induced synthesis of polyamines precedes fusion. The inhibition by MGBG of the 1‐α,25‐(OH)2D3‐induced fusion was restored completely by adding 1μMspermidine or spermine or 100μMputrescine. None of the polyamines alone induced fusion. MGBG suppressed the 1‐α,25‐(OH)2D3‐induced incorporation of [3H]‐leucine into the trichloroacetic acid‐insoluble fraction in macrophages, but its inhibitory effect was restored completely by adding 1μMspermidine. When macrophages were incubated with [14C]‐ornithine, the polyamine that accumulated most was [14C]‐spermidine. 1‐α,25‐(OH)2D3further enhanced the accumulation of [14C]‐spermidine. The accumulation of [14C]‐putrescine and spermine was not appreciably altered by the 1‐α,25‐(OH)2D3treatment. Adding MGBG almost completely suppressed the accumulation of [14C]‐spermidine and spermine, but it enhanced the accumulation of [14C]‐putrescine considerably. These results indicate that spermidine or spermine is an important intracellular mediator of the 1‐α,25‐(OH

ISSN:0884-0431    

DOI:10.1002/jbmr.5650010211

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1986

数据来源: WILEY