bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of vitamin a on bone resorption: Evidence for direct stimulation of isolated chicken osteoclasts by retinol and retinoic acid
Authors: Oreffo Richard O.C. , Teti A. , Triffitt J.T. , Francis M.J.O. , Carano A. , Dr. Zallone Zambonin A. 
Published: February 2010

Abstract
The effects of retinol (vitamin A) and retinoic acid on primary cultures of isolated chicken osteoclasts have been studied. The experiments were performed to establish the direct actions of these two agents on the organization of cytoskeletal structures, on the acid phosphatase contents, and on the bone resorption activities of these cells. The results showed that by treating the cultures with retinol or retinoic acid, from 10−8 to 10−5M, there were dose-related responses of the osteoclasts. Adhesion to the substratum was stimulated by increasing the number of cells exhibiting the specialized dot-like adhesion structures, or podosomes, which represent the active part of the sealing zone. The treatments also induced rearrangement of the microtubular patterns with reversible depolymerization of microtubules. Acid phosphatase activity was significantly higher both in vitamin A-treated osteoclasts and in their media. When [3H]proline-labeled bone particles were added to the retinoid-treated osteoclasts, the release of [3H]proline was increased significantly compared to controls. These results suggest that the two vitamin A metabolites cause several modifications of the metabolic status of isolated osteoclasts that result in augmented rates of bone resorption.
Inhibition by phenytoin ofin vitrosecretion of calcitonin from rat thyroid glands and cultured rat C cells
Authors: Cooper Cary W. , Yi Su-Jin , Seitz Patricia K. 
Published: February 2010

AbstractBaby rat thyroid glands and cultured rat medullary carcinoma C cells were incubated acutely with phenytoin (38–100 μM), and the calcitonin (CT) secreted into the serum-free medium was measured by radioimmunoassay (RIA). Phenytoin did not alter CT release from glands or C cells incubated in 1 mM Ca, but, when Ca was raised to 1.75 or 2.5 mM, a marked inhibitory effect of phenytoin was apparent. The inhibitory effect could be negated by including 10 μM BAY-K-8644 in the medium. Inhibitory effects on CT release also were obtained with 100 μM trifluoperazine or 100 μM nitrendipine, and these inhibitory effects also were counteracted by 10 μM BAY-K-8644. The results show that clinically relevant amounts of phenytoin can inhibit CT release, perhaps by interfering with C-cell Ca channels or by inhibiting calmodulin-dependent processes.
Factor derived from human lung carcinoma associated with hypercalcemia mimics the effects of parathyroid hormone on phosphate transport in cultured renal epithelia
Authors: Pizurki L. , Rizzoli R. , Caverzasio J. , Mundy G. , Bonjour J.-P. 
Published: February 2010

Abstract
A decrease in renal tubular reabsorption of inorganic phosphate (Pi) can be observed in hypercalcemia of malignancy. In the present study we investigated the effect of serum-free conditioned medium (CM) from cells, derived from a lung carcinoma (BEN) of a hypercalcemic patient, and of PTH on cyclic AMP (cAMP) production and sodium-dependent Pi transport (NaPiT) in epithelia of two renal cell lines. In opossum kidney cells (OK), PTH is known to enhance cAMP production and inhibit NaPiT; in contrast, in LLC-PK1 cells, PTH has no effect on NaPiT since this kidney cell line is devoid of PTH receptors. In OK cells, BEN CM induced a three- to fourfold increase of cAMP production, which was blunted by the PTH inhibitors bPTH(3–34) and bPTH(7–34). NaPiT, as assessed by measuring the initial rate of Pi uptake, was inhibited in a dose-dependent manner by BEN CM, with an effect maximal between 1h30 and 6 hr of incubation (40 ± 4% and 47 ± 4%, respectively), corresponding to the effect produced by 1–3 nM bPTH(1–34). The Na-dependent transport of a glucose analog was affected neither by BEN CM nor by PTH. In LLC-PK1 cells, neither BEN CM nor PTH altered cAMP production nor NaPiT after 1h30 of incubation. At 6 hr, BEN CM caused a slight decrease in NaPiT. In conclusion, these results constitute the first evidence of a direct and selective inhibition by tumor-derived factor(s) of NaPiT in cultured renal epithelia. Most of the renal NaPiT inhibitory activity produced by the lung tumor required the presence of a PTH receptor-adenylate cyclase system. This study also indicates that cultured renal epithelia can represent quite valuable tools for characterizing the activity of tumor-derived factors on kidney functions.
Changes in serum levels of type I and III procollagen extension peptides during infusion of human parathyroid hormone fragment (1–34)
Authors: Dr. Simon Lee S. , Slovik David M. , Neer Robert M. , Krane Stephen M. 
Published: February 2010

Abstract
Parathyroid hormone (PTH) inhibits collagen synthesis in vitro, in organ or cell culture and cell-free translation systems. We have designed studies to measure the effects of PTH on collagen synthesis in vivo in humans, utilizing measurements of the serum levels of procollagen extension peptides during and after infusion of synthetic human PTH (hPTH) fragment (1–34). Radioimmunoassays for the carboxy-terminal peptide of type I procollagen (pColl-C) and the amino-terminal peptide of type III procollagen (pColl-III-N) were used to measure acute changes in serum during and after hPTH(1–34). In all six osteoporotic subjects and two normal individuals, serum levels of pColl-I-C were decreased by 16 hr of infusion and returned towards normal 14 hr after the infusion was discontinued; serum levels of pColl-III-N did not change significantly during the infusion, but were increased at 14 hr after the infusion was discontinued. The PTH-induced decrease in levels of pColl-I-C correlated with an increase in blood levels of ionized calcium. In all but two subjects the serum levels of 1,25-dihydroxy vitamin D [1,25(OH)2D] were also increased during the period when serum levels of pColl-I-C were decreased. These results are compatible with the conclusion that infusion of PTH acutely inhibits type I (bone) collagen synthesis, but not type III collagen synthesis. These effects could be direct or indirect, related in part to PTH-induced increased 1-α-hydroxylation of 25-(OH) vitamin D and the resultant increased serum levels of 1,25(OH)2D.
One year's treatment of paget's disease of bone by synthetic salmon calcitonin as a nasal spray
Authors: Dr. Reginster J.Y. , Jeugmans-Huynen A.M. , Albert A. , Denis D. , Franchimont P. 
Published: February 2010

Abstract
The effectiveness of synthetic salmon calcitonin (SCT) administered as a nasal spray was assessed via clinical, biological, and radiological variables in 17 previously untreated Pagetic patients over a 1-year course of therapy. The results showed a highly significant decrease of serum alkaline phosphatase (S-ALP) (p &lt; 0.05 after 1 month of treatment) and of the urinary hydroxyproline/creatinine ratio (OH/Cr) (p &lt; 0.01 after 1 month of treatment). For the whole group, the mean decrease in S-ALP was 37 ± 4% (SEM) after 6 months (p &lt; 0.01) and 31 ± 5% after 1 year (p &lt; 0.01). The mean fall in OH/Cr was 35 ± 6% (SEM) (p &lt; 0.01) and 37 ± 7% (p &lt; 0.01) after 6 and 12 months, respectively. None of the usual side-effects of SCT were reported and local tolerance was excellent throughout the study.
Forearm bone loss in hemiplegia: A model for the study of immobilization osteoporosis
Authors: Dr. Prince R.L. , Price R.I. , Ho S. 
Published: February 2010

Abstract
Hemiplegia is associated with excessive bone loss in the paralyzed arm. The forearm bone mineral content was measured at a proximal cortical site and a distal trabecular site of both the normal and hemiplegic arms in 74 patients with hemiplegia. By comparing the ratios of bone mineral content in the two arms, the effect of immobilization could be quantitated independently of the large population variance in bone mineral content. Bone loss, estimated from this single comparison of bone mineral content in the normal and hemiplegic arms, at the trabecular and cortical sites was positively correlated with the duration of stroke and negatively correlated with reduction in forearm function. At the trabecular site females had a proportionately greater bone loss than males, indicating an interaction between gender and immobilization associated bone loss at this site. The regression line of excess bone loss in the hemiplegic limb against time had a negative slope of 1.3% and 1.5% a year of the starting value for the trabecular and cortical sites, respectively, over the 15 years studied. This study indicates that a reduction in function is associated with significant bone loss occurring over prolonged periods that may account, at least in part, for the significant osteoporosis seen in elderly people and in subjects with conditions resulting in reduced mobility such as arthritis, obstructive airways disease, and neurological disease.
Consistent patterns of changing hormone responsiveness during continuous culture of cloned rat calvaria cells
Authors: Dr. Aubin J.E. , Tertinegg I. , Ber R. , Heersche J.N.M. 
Published: February 2010

Abstract
The loss of responsiveness to hormones in cell populations is a fundamental problem in cell biology and aging. We have studied this process in cloned rat calvaria (RC) bone cell populations maintained in exponential growth in long-term culture in α-minimal essential medium supplemented with fetal bovine serum. At various times after cloning, the populations were tested for their ability to respond to parathyroid hormone (PTH), prostaglandin E2 (PGE2), and L-isoproterenol (IPT) with an increase in intracellular cAMP. Clone RCB 2.2, which was originally responsive to PTH but not PGE2, maintained this characteristic throughout 14 mo of culture, after which PTH responsiveness was gradually lost and a concomitant increase in responsiveness to PGE2 was observed. Subsequently, PGE2 responsiveness was also lost; however, continued response to IPT indicated the presence of a hormone-sensitive adenylate cyclase. A similar pattern of hormone responsiveness was observed when a number of frozen stocks of RCB 2.2 cells were thawed and the cells were again maintained in continuous culture. That this pattern of phenotypic change was not unique to clone RCB 2.2 was verified by assessing the hormone responses in other independently selected clones. Although the precise time sequence for hormone response changes was not constant, in all cases the pattern of hormone response changes was similar: i.e., PTH response was always lost and PGE2 response often first increased and then also was lost, despite the maintenance of response to IPT. These data indicate that clonal hormone-responsive populations can reproducibly give rise to unresponsive populations in an ordered series of phenotypic changes. Changes in response to the hormones tested did not appear to be concomitant with changes in other phenotypic properties, e.g., decrease in alkaline phosphatase activity.
Quantitative bone histomorphometry in nude mice bearing a human squamous cell lung cancer
Authors: Kukreja Subhash C. , Rosol Thomas J. , Shevrin Daniel H. , York Patricia A. 
Published: February 2010

AbstractWe performed quantitative bone histomorphometry on lumbar vertebrae in hypercalcemic tumor-bearing athymic mice carrying a human squamous cell carcinoma. For comparison, studies were also performed in athymic mice that received bovine 1–34 parathyroid hormone (PTH) infusion at the rate of 0.167 μg/hr for 7 days. In both the PTH-infused and tumor-bearing animals, percent cortical and total bone areas were significantly reduced as compared to controls, whereas trabecular bone was significantly reduced only in the tumor-bearing animals. Trabecular perimeter lined by osteoclasts was significantly increased in both tumor-bearing (1.7-fold) and PTH-infused animals (2.8-fold) compared to control mice. Trabecular perimeter lined by active osteoblasts was significantly reduced in the tumor-bearing animals (to 42% of control) and unchanged in the PTH-infused animals (97% of control). Tumor-bearing animals had significantly reduced resorptive as well as formative surfaces as compared to the PTH-infused animals. Dynamic histomorphometry revealed a marked reduction in bone formation rate (23% of control) in the tumor-bearing animals. The studies therefore demonstrate a marked inhibition of bone formation associated with increased bone resorption in this model of hypercalcemia of malignancy. These observations are similar to those seen in the human syndrome.
Effects of oxidation of human parathyroid hormone on its biological activity in continuously infused, thyroparathyroidectomized rats
Authors: Dr. Horiuchi Noboru 
Published: February 2010

Abstract
The effect of oxidation of human parathyroid hormone 1–34 (hPTH 1–34) on the hormone's biological activity was assessed in vivo using a multiparameter, thyroparathyroidectomized (TPTX) rat model. The peptide was oxidized by treatment with hydrogen peroxide, and the oxidized form (8,18-methionine sulfoxide) was isolated by reverse-phase HPLC. Vitamin D-deficienf rats were infused with either intact or oxidized hormone along with a 5 mM calcium chloride solution for 4 or 18 hr. Infusion of nonoxidized hormone (0.1–0.8 nmoles/hr) resulted in dose-dependent increases in serum calcium, decreases in serum phosphate, decreases in urine calcium, increases in urine phosphate and cAMP, and increased renal 1,25-dihydroxyvitamin D3 (1,25 (OH)2D3) production. Oxidized PTH infused at doses up to 0.8 nmole/hr had no effect on any of these parameters. To assess the effect of oxidation on the ability of PTH to inhibit the production of the 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), the infusion protocol was performed in vitamin D-deficient rats repleted with 1,25(OH)2D3 by injection. In these experiments, intact hormone markedly suppressed 24,25(OH)2D3 production, whereas the oxidized form was without effect. We conclude that intact methionine residues at positions 8 and 18 of hPTH 1–34 are necessary for all its major biological actions, including its effect on the renal metabolism of 25-hydroxyvitamin D3(25(OH)D3).
Aluminum intoxication in vitamin D-deficient rats: Studies of bone aluminum localization and histomorphometry before and after vitamin D repletion
Authors: Dr. Hodsman A.B. , Steer B.M. , Arsenault A.L. 
Published: February 2010

Abstract
Aluminum accumulation by both dialysis patients and nonuremic patients, requiring chronic total parenteral nutrition, may be an etiological factor in the development of severe osteomalacia. To study the role of aluminum toxicity in bone, further experiments have been conducted in the nonuremic, vitamin D-deficient rat. Weanling rats were raised on vitamin D-deficient diets, and half received parenteral aluminum (5 mg/wk), for 30 days. In the first experiment low doses of 25-OH cholecalciferol (500 ng/week) were given subcutaneously for a further 30 days. Control rats were maintained on a similar protocol, but were supplemented with cholecalciferol (5 μg/week) from the outset until sacrifice at 60 days. In the second experiment a single bolus of cholecalciferol (5 μ/g) was given to study short-term changes in serum biochemistry and bone histology at 96 hr. Quantitative bone histomorphometric analyses of the proximal tibial metaphysis were made in all experimental groups. In the experimental vitamin D-deficient group, with the highest bone aluminum content (as assessed by extraction of whole bone aluminum), X-ray microanalysis was performed to determine the distribution of aluminum in bone tissue and bone cell organelles. The results showed that control rats treated with prolonged aluminum therapy (30 mg over 60 days) had evidence of both reduced osteoid matrix synthesis and mineralization. However, in vitamin D-deficient rats, there was no evidence that aluminum exacerbated the osteomalacic lesion, even though there was histochemical evidence of aluminum deposition at the bone-osteoid interface. X-ray microanalysis confirmed the presence of aluminum at this site, but did not reveal significant peaks of aluminum either in mineralized bone or within osteoblasts. In both experiments, vitamin D-induced osteomalacia was rapidly reversed by both low-dose 25-OH cholecalciferol and bolus cholecalciferol, suggesting that aluminum accumulation alone does not lead to impaired mineralization if other conditions favoring bone metabolism are present. In these experiments, secondary hyperparathyroidism may have been one such factor in explaining the failure of bone aluminum accumulation to impair bone mineralization in vitamin D-deficient rats when compared to vitamin D-replete controls. Although several animal models of aluminum toxicity have been explored, clearly the experimental conditions, dose, and duration of aluminum administration, and the degree of secondary hyperparathyroidism, are critical factors in determining whether aluminum accumulation in bone results in significant pathology.
Indomethacin inhibition of tenotomy-induced bone resorption in rats
Authors: Dr. Thompson D.D. , Rodan G.A. 
Published: February 2010

Abstract
Loss of biomechanical function results in rapid bone loss. This study assesses the role of arachidonic acid metabolites in immobilization-related osteopenia. A hind limb of the rat was immobilized by knee tenotomy and bone resorption and formation parameters were quantitated by histological methods in indomethacin-treated (0.5 mg/kg per day) and vehicle-treated animals. Control animals sacrificed 30, 72, and 240 hr post-tenotomy revealed a significant increase in osteoclast number (30 hr) and resorption surfaces (72 hr) and a decrease in trabecular bone volume (240 hr) in the tenotomized tibiae. In the indomethacin-treated tibial metaphysis, no significant differences were noted for these parameters by comparison to the nontenotomized leg. Bone formation parameters remained reduced in the tenotomized legs of both the indomethacin and vehicle-treated groups compared to the control legs. Indomethacin inhibited bone resorption, but did not prevent the decrease in bone formation produced by immobilization over the 10 days of these experiments.
Bone status of senescent female rats: Chemical, morphometric, and biomechanical analyses
Authors: Kiebzak Gary M. , Smith Ronald , Howe Juliette C. , Gundberg Caren M. , Dr. Sacktor Bertram 
Published: February 2010

Abstract
The bone status of female rats, 6, 12, and 24 months of age was examined. Femur Ca, Pi, and osteocalcin contents, as well as biomechanical properties, were measured and correlated to physical indices and serum chemistry. Diaphyseal Ca, Pi, and osteocalcin did not change significantly with increasing age. Serum Ca and Pi concentrations were not altered in the aged rat. Immunoreactive parathyroid hormone (PTH) levels increased significantly with age, when analyzed by linear regression. Serum osteocalcin decreased progressively from 6 to 12 months (-21%) and from 12 to 24 months (-23%). Maximum breaking force required to fracture femurs at midshaft did not change with senescence. Hence, the strength of the femurs as an intact organ was not compromised in aging. However, ultimate stress, a parameter that normalizes for differences in bone geometry and size, decreased 14% from 12 to 24 months. Changes in other biomechanical parameters, including yield and ultimate deformation, strain, and modulus of elasticity, were relatively small, but statistically significant, or were negligible. Morphometric measurements indicated a progressive age-related increase in second moment of area and cortical area. Medullary area did not change with age. Therefore, strength of the intact femur was maintained by architectural compensations, although normalized tissue strength decreased in senescence. The bone status and Ca/Pi homeostasis of the female rat were compared to similar findings, reported previously, for the male animal. The results suggest that bone status and mineral metabolism were compromised in the aged female rat, but the magnitude of change was less than that found for the senescent male rat.
Evidence of a probable role for 25-hydroxyvitamin D in the regulation of human calcium metabolism
Authors: Dr. Bell Norman H. , Epstein Sol , Shary Judith , Greene Virginia , Oexmann Mary Joan , Shaw Sheryl 
Published: February 2010

Abstract
1,25-Dihydroxyvitamin D [1,25-(OH)2D] is the principal mediator of the biologic effects of vitamin D. We showed previously that obese white subjects have low serum vitamin D and 25-hydroxyvitamin D (25-OHD) with increased serum-immunoreactive parathyroid hormone (PTH) and 1,25-(OH)2D, low urinary calcium, and increased urinary cyclic adenosine 3′,5′-monophosphate (cyclic AMP) compared with nonobese white individuals. To determine whether 25-OHD modulates calcium metabolism, the effects of 25-OHD3, 40–100 μg/day for 9 days, were compared in seven obese and seven nonobese white subjects who were between the ages of 20 and 34 years. Each of them was hospitalized on a metabolic ward and given a constant daily diet that contained 400 mg calcium, 900 mg phosphate, and 18 mEq magnesium. Whereas 25-OHD3 increased mean serum 25-OHD from 7 ± 1 to 37 ± 5 ng/ml (P &lt; 0.01) and urinary calcium from 102 ± 18 to 146 ± 17 mg/day (P &lt; 0.001) and decreased mean serum 1,25-(OH)2D from 40 ± 2 to 28 ± 2 pg/ml (P &lt; 0.01) and urinary cyclic AMP from 3.23 ± 0.57 to 2.00 ± 0.17 nM/dl GF (P &lt; 0.05), it did not change mean serum calcium, ionized calcium, phosphate, magnesium, immunoreactive PTH or urinary phosphate, or creatinine clearance in the obese subjects. In contrast, 25-OHD3 increased mean serum 25-OHD from 16 ± 1 to 46 ± 4 pg/ml (P &lt; 0.001) but did not alter mean serum 1,25-(OH)2D or urinary calcium or cyclic AMP in the nonobese subjects. Metabolic balance studies carried out in two of the obese subjects showed that 25-OHD3 increased serum 25-OHD and urinary calcium and lowered serum 1,25-(OH)2D. The findings are interpreted to mean that elevated serum 1,25-(OH)2D and urinary cyclic AMP and low urinary calcium in obese subjects result from a deficiency of vitamin D and 25-OHD, that these changes are reversed by 25-OHD3, and that in humans 25-OHD has a modest role in the regulation of calcium metabolism that is independent of the regulation by 1,25-(OH)2D.
The relationship between long bone growth rate and duodenal calcium transport in female rats
Authors: Dr. Thomas Mary L. , Hope William G. , Ibarra Michael J. 
Published: February 2010

Abstract
Studies were carried out to determine the relationship between long bone growth rate and duodenal calcium (Ca) transport in female rats and the regulation of these two parameters by ovarian hormones. Female rats were ovariectomized (ovx) at 6 weeks of age. Some animals were implanted with silastic implants containing either estradiol or progesterone at the time of ovx. Studies were carried out 3 weeks later when the rats were 9 weeks old. Ovx resulted in an increase in long bone growth rate and duodenal Ca transport without any alteration in circulating levels of parathyroid hormone or 1,25-dihydroxyvitamin D [1,25-(OH)2D]. Animals receiving estradiol exhibited decreased long bone growth rate and duodenal Ca transport relative to ovx animals. These animals were mildly hypercalcemic and had lower levels of 1,25-(OH)2D than ovx or intact animals. The results of these studies suggest that the effects of ovarian hormone status on duodenal Ca transport are more closely related to long bone growth rate than to circulating levels of 1,25-(OH)2D. Further studies are required to determine whether the two parameters are coregulated by some as-yet-unidentified factor or whether bone growth is able to emit some signal, directly or indirectly, to increase duodenal Ca transport.