bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence for a toxic effect of aluminum on osteoblasts: A histomorphometric study in hemodialysis patients with aplastic bone disease
Authors: Parisien M. , Charhon S.A. , Arlot M. , Mainetti E. , Chavassieux P. , Chapuy M.C. , Meunier P.J. 
Published: February 2010

Abstract
To evaluate the potential role of aluminum (Al) in a subset of dialysis patients with aplastic bone disease, we have studied tetracycline-labeled bone biopsies of 32 patients (22 males and 10 females, 45–73 years) on maintenance hemodialysis. Selection criteria included normal resorption surfaces (RS) and osteoid thickness. Eleven patients (Group I) had no stainable bone Al (Al -; 61.7 ± 7.2 years) and 21 (Group II) had stainable bone Al (Al +; 57.7 ± 6.8 years). Serum Al was normal to slightly elevated in Group I, but significantly higher in Group II (p &lt; 0.01). Al surfaces (AlS), undetectable in Group I, were 67.8 ± 17.9% in Group II. Bone Al content (BAC) was much lower in Group I than in Group II (14.8 ± 3.7 vs. 113.8 ± 100.2 μg/g, p &lt; 0.01), but higher in Group I than in controls (p &lt; 0.05). Extensive thin osteoid seams were present in Group II. AlS was correlated with OS (r = 0.56, p &lt; 0.001) and OV (r = 0.48, p &lt; 0.01). Labeled surfaces were decreased in both groups. Labeled osteoid surfaces (TLS/OS) were below 2 SD of the mean control values in 96% of patients and calcification rate (CR) was depressed below 0.20 μm/day in 44% of patients. Bone formation rate (BFR) was strikingly depressed, values being below one SD of the mean control value in 92–100% of patients at both levels and below 2 SD of the mean in 82% of patients at BMU levels. Mineralization lag time (OMP) was markedly prolonged above 2 SD of controls in 89% of patients. A major observation was in the extent of osteoblast osteoid surfaces (OblS/OS) which was found significantly different in Group I (34.2%) than in Group II (15%) (p &lt; 0.001); these differences were consistently found in osteoid surfaces covered by different morphological types of osteoblasts (plump, intermediate, and flat). Negative correlations were found between AlS and OblS/OS (r = −0.57, p &lt; 0.001), intermediate OblS/OS (r = −0.38, p &lt; 0.05) and flat OblS/OS (r = −0.56, p &lt; 0.01). These findings indicate an impairment of osteoblastic function, with depression of bone formation at all levels, and strongly suggest a toxic effect of Al on osteoblasts.
Effects of transforming growth factor type beta upon bone cell populations grown either in monolayer or semisolid medium
Authors: Dr. Guenther Harald L. , Cecchini Marco G. , Elford Peter R. , Fleisch Herbert 
Published: February 2010

Abstract
Bone has been shown to store large amounts of transforming growth factor type beta (TGFβ) and this has recently been found to be synthesized by bone-forming cells. We report on studies undertaken to examine the effects of platelet-derived TGFβ on different bone cell populations, isolated from 1-day postnatal rat calvaria by sequential enzymatic digestion. In addition, we tried to determine which of these cell populations synthesize TGFβ. In this regard, evidence was collected to indicate that cell populations which were shown to be enriched with osteoblast-like cells synthesize TGFβ. Although the production of the factor appeared to be limited to a particular cell type, its action was found to be of a more general character, as all cell populations were found to respond to TGFβ. Contrary to earlier reports, TGFβ was shown to be inhibitory upon cell proliferation. In this context, growth of cells released during early digestions was reduced considerably more than growth of those released during late digestions. Studies on the effect upon protein synthesis revealed that TGFβ specifically inhibited collagen but not the synthesis of noncollagenous proteins. The synthesis of collagen was altered to a greater extent in cells isolated during late digestions than in cells of the early populations. Further information on the TGFβ-mediated effects on bone cell biology was provided by data showing that both alkaline phosphatase and cAMP production in response to PTH was greatly reduced by TGFβ. Finally, experiments performed to determine whether TGFβ induces any of the bone cell populations to acquire the transformed phenotype revealed that only populations previously shown to be enriched with osteoblast-like cells formed colonies in soft agarose. In summary, differential action of TGFβ on various bone cell populations observed in these studies and its abundance in bone suggests that this polypeptide factor may constitute an important element in events that balance the function of bone cells according to the physiological requirements of bone.
Glucose transport in osteoblast-enriched bone explants: Characterization and insulin regulation
Authors: Dr. Hahn Theodore J. , Westbrook Scott L. , Sullivan Theresa L. , Goodman William G. , Halstead Linda R. 
Published: February 2010

Abstract
Insulin has potent effects on osteoblast function both in vivo and in vitro. In various insulin-sensitive tissues, stimulation of glucose transport and metabolism are hallmarks of insulin action, and have been postulated to play a role in insulin regulation of cellular function. However, insulin effects on glucose metabolism in osteoblast-like cells have not been demonstrated. Therefore we examined the in vitro effects of insulin on hexose uptake in an osteoblast-enriched rat bone explant preparation. Uniform 5-mm-diameter punch sections were obtained from the cartilage-free frontal portions of the calvaria of 3-day-old rats, and the periosteum was removed. The resulting sections contained a highly enriched population of osteoblast-like cells as determined by histologic criteria, elimination of calcitonin-stimulatable cAMP generation, and enhancement of PTH-stimulatable cAMP generation per microgram of DNA. Sections were incubated for 24 hr at 37°C in BGJb medium and then transferred to modified glucose-free Krebs-Ringer bicarbonate buffer for 2-deoxy-D-glucose (2-DG) uptake studies. 3H-2-DG uptake was linear with time over 60 min, temperature sensitive, and inhibited by 5 mA/phloridzin. Kinetic analysis of 2-DG uptake at 25°C demonstrated a saturable transport mechanism with a Km of 2.2 mM, similar to that observed for 2-DG transport in other tissues. Studies of competitive inhibition by other sugars demonstrated a transport specificity for 2-DG that was comparable to that previously observed in fat and muscle cells. 2-DG uptake was rapidly stimulated by insulin (0.5 nM-1 μM), with maximal insulin effect observed at 50 nM. Concanavalin A (10–50 μg/ml) produced a similar stimulation of 2-DG transport. Both basal and insulin-stimulated uptake were inhibited reversibly by cytochalasin B (50 μM). Insulin stimulation of 2-DG uptake was the result of increased transport Vmax, with Km remaining constant. These studies provide the first demonstration that the cell population of osteoblast-enriched bone explants possesses an insulin-stimulatable glucose transport system with characteristics similar to those found in other insuln-sensitive tissues.
Transfusion of carbonic anhydrase-replete erythrocytes fails to correct the acidification defect in the syndrome of osteopetrosis, renal tubular acidosis, and cerebral calcification (Carbonic Anhydrase-II Deficiency)
Authors: Dr. Whyte Michael P. , Lee Hamm Lotuce , Sly William S. 
Published: February 2010

Abstract
We explored the effects of transfusion of carbonic anhydrase II (CA-II)-replete erythrocytes on systemic pH, serum electrolytes, and urinary acidification of a patient with CA-II deficiency. Pretransfusion studies documented hyperchloremic acidosis, increased urinary pH with decreased titratable acidity, and profound CA-II deficiency in erythrocytes. During transfusion, CA-II in circulating erythrocytes increased to above the half-normal levels seen in asymptomatic heterozygote carriers of CA-II deficiency. However, no significant change occurred in venous, arterial or urinary pH, serum electrolytes, and urinary acid excretion during the transfusion or during the subsequent 60 hr of observation. These studies argue that the renal acidification defect in CA-II deficiency results from deficiency of CA-II in the renal parenchyma, and is not secondary to deficiency of CA-II in erythrocytes. Bone marrow transplantation is not a promising approach to correct the renal manifestations of CA-II deficiency.
Further biochemical and molecular characterization of primary rat parietal bone cell cultures
Authors: Dr. McCarthy Thomas L. , Centrella Michael , Canalis Ernesto 
Published: February 2010

Abstract
Primary bone cell cultures are used widely to examine the regulation of bone metabolism by growth factors and hormones. Characterization of this model system is now being conducted at the molecular level to define modulation of gene expression. Cells were obtained from rat parietal bone by sequential collagenase digestions. Cell populations were evaluated for bone-related products, including collagen isoform expression and mRNA levels, alkaline phosphatase activity, and osteocalcin production. Serum-deprived, confluent cultures of the first and second collagenase-released populations produced a lower percentage of total protein as collagen than the third, fourth, and fifth populations, while co-culturing the third through fifth populations resulted in the highest level. Collagen typing on SDS-polyacrylamide gels revealed an abundance of mature type I collagen in all cell populations; type III collagen synthesis was undetectable by this method. This is in contrast to the presence of cytoplasmic mRNA for both type I and type III collagen in all cell populations, suggesting post-transcriptional modulation of type III collagen synthesis. The expression of alkaline phosphatase and osteocalcin was highest in cultures of later released cells, indicating that these cell populations display phenotypic characteristics associated with cells of the osteoblast lineage.
The effects of phenytoin on calcium uptake in osteoblastic cells
Authors: Dr. Dziak R. , Vernillo A. , Rifkin B. 
Published: February 2010

AbstractThe effects of Phenytoin (diphenylhydantoin, DPH) on calcium uptake in osteoblastic cells were studied to elucidate the potential mechanism of action of this antiepileptic drug on bone metabolism. Preincubation of the human osteoblastic osteosarcoma) cell line, SaOS-2, and normal rat osteoblastic cells with DPH decreased basal calcium uptake. This inhibition occurred at DPH doses from 0.1 to 50 μg/ml. Parathyroid hormone (PTH) and prostaglandin E2 (PGE2) increased calcium uptake in the SaOS-2 cell line. Following preincubation with DPH, calcium uptake in cells treated with PTH or PGE2 did not exceed control levels. However, significant increases in the PTH- or PGE2-treated + DPH-pretreated cells compared to DPH pretreatment alone were still observed. These studies indicate that DPH induces decreases in osteoblastic calcium influx and they add further information on the possible mode of action of this drug on bone.
The effects of forskolin and calcium ionophore A23187 on secretion and cytoplasmic RNA levels of Chromogranin-A and calcitonin
Authors: Murray Samuel S. , Burton Douglas W. , Dr. Deftos Leonard J. 
Published: February 2010

Abstract
We have studied the regulation of the secretion and cytoplasmic RNA levels of calcitonin (CT) and Chromogranin-A (CgA) to determine if the biosynthesis and secretion of these two substances are controlled in a coordinated fashion. The studies were conducted in two cell lines, a medullary thryoid carcinoma (MTC) cell line and a lung tumor (BEN) cell line. Both cell types secrete CT and CgA. Forskolin treatment resulted in a significant increase in the secretion of CT and CgA in each cell line and in CT-specific cytoplasmic RNA in the MTC cell line. Treatment with calcium ionophore A23187 resulted in significantly increased secretion of both substances in the lung tumor cells but not in the medullary thyroid carcinoma cells. A significant increase in CT-specific or CgA-specific cytoplasmic RNA was not seen in either cell line. We conclude that the secretion of CT and CgA are regulated in a coordinated fashion in these cell lines through processes that are calcium-mediated and processes that involve cyclic AMP-dependent protein kinase A. However, each of these regulatory pathways is not always operative in a given tissue. The coordinate regulation of the secretion of CT and CgA supports the hypothesis that CgA participates in the secretory process of its associated hormones.
Parathyroid hormone receptors in human dermal fibroblasts: Structural and functional characterization
Authors: Pun K.K. , Arnaud Claude D. , Dr. Nissenson Robert A. 
Published: February 2010

Abstract
Previous studies have established the presence of parathyroid hormone (PTH)-sensitive adenylate cyclase activity in cultured human skin fibroblasts. The present study was undertaken to identify and quantitate PTH receptors directly in such cells. Human dermal fibroblast cell line CRL 1564 was found to possess specific binding sites for [125I]PTH(1–34). These sites bound PTH selectively; bovine and human PTH(1–34) and PTH(1–84) competed for [125I]PTH(1-34) binding sites, whereas the unrelated peptides calcitonin, insulin, AVP, angiotensin II, and ACTH(1–24) were inactive even at micromolar concentrations. Competitive binding experiments demonstrated the presence of binding site heterogeneity. These data fit a “two-site” model (p &lt; 0.001) in which one binding component has high affinity (Kd = 2.5 ng/ml = 0.6 nM) and low capacity (104 sites/cell) while the other has low affinity (Kd = 5.9 μg/ml = 1.5 μM) and high capacity (&gt;107 sites/cell). Similar high- and low-affinity [125I]bPTH(1–34) binding sites were seen also in CRL 1564 membranes containing a PTH-responsive adenylate cyclase. The Kd of the high-affinity sites was identical to the concentration of unlabeled bPTH(1–34) (4.2 ng/ml = 1.0 nM) required to half-maximally elevated cyclic AMP in CRL 1564 cells. Affinity labeling of specific PTH binding sites revealed the presence of multiple components with Mrs of 85, 70, 40, 33, and 23 kD on SDS-PAGE. Competition experiments did not disclose structurally discrete high- and low-affinity sites. Thus, structurally homologous PTH receptors in human skin fibroblasts apparently can assume two affinity states: (i) a high-affinity state coupled to adenylate cyclase and (ii) a low-affinity state that may represent uncoupled receptors.
Malignant osteoporosis and defective immunoregulation
Authors: Rubin Karen R. , Ballow Mark , Baron Roland , Greenstein Robert M. , Raisz Lawrence G. , Rowe David W. 
Published: February 2010

Abstract
The linkage between immune cells and the osteoclast has become partially understood in the laboratory, but the full spectrum of clinical disorders of this relationship remain to be elucidated. We report a 29-month-old girl with recurrent infections and multiple fractures. Immune evaluation showed normal quantitative serum immunoglobulins but absent antibodies to the respiratory viruses and tetanus toxoid and decreased in vitro polyclonal-induced immunoglobulin production. Further analysis in vitro with separated lymphocyte populations showed normal B cell function but markedly increased suppressor T cell activity. The bone evaluation showed diffuse osteopenia on x-ray. Serum calcium, phosphorus, PTH, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were normal for age. Urinary calcium excretion (24 h) was, however, two times normal. An iliac crest biopsy confirmed the presence of extreme osteopenia with normal mineralization and numerous small atypical osteoclasts resorbing the bone. No circulating plasma resorptive activity was demonstrated. Calcitonin therapy markedly diminished the patient's hypercalciuria. We speculate that this patient's increased bone resorption, decreased bone formation, and suppressor activity may be linked by a common pathway involving the abnormal function of immune cells. Since no similar constellation of findings has been previously reported, this case may represent a new congenital disorder: severe osteopenia associated with increased osteoclast activity in association with a defect in T cell immunoregulation.
Differences in the kinetics of the mineralization process in endochondral and intramembranous osteogenesis in human fetal development
Authors: Dr. Dziedzic-Goclawska A. , Emerich J. , Grzesik W. , Stachowicz W. , Michalik J. , Ostrowski K. 
Published: February 2010

Abstract
About 300 samples of bone tissue from femoral diaphyses and from parietal bones of calvaria were collected from human fetuses aged from 6–8 to 40–41 weeks in order to compare the kinetics of the mineralization process in endochondral and intramembranous bone formation. The crystallinity of bone mineral was evaluated by the method based on electron spin resonance (ESR) spectrometry, and mineral content was measured after ashing of the samples.
Highly significant differences in the kinetics of deposition of mineral (ash content) and maturation of deposited mineral (crystallinity coefficient) were found between parietal bones and femoral diaphyses in the course of fetal development. In the early stages of development (6–8 to 10–12 weeks), the content of mineral and its crystallinity in parietal bones were significantly lower than in femoral diaphyses. In the parietal bones a gradual increase in both values was observed until they reached a plateau at the age of 30 weeks. On the other hand, in femoral diaphyses of 6–8-week-old fetuses mineral content was high and deposited mineral showed a high degree of crystallinity. Both these values did not change significantly until birth. The differences in kinetics of the mineralization process between the weight-bearing bones and bones that are not exposed to the influence of strong external forces are most probably genetically conditioned. The collected data supply embryological information and might be used in the future for evaluation of pathologic changes in skeletal development.
Early vertebral trabecular bone loss in normal premenopausal women
Authors: Buchanan James R. , Myers Cathleen , Lloyd Tom , Greer Robert B. 
Published: February 2010

Abstract
The precise timing for the onset of trabecular bone loss in women is a matter of controversy. To address this issue, we studied the relationship between age and vertebral trabecular bone density (measured by computed tomography) in 74 healthy premenopausal women from 18 to 48 years old. We also measured radial cortical bone density (by single photon absorptiometry) in 28 of these subjects.
Trabecular bone density levels (milligrams per milliliter, mean ± standard error of the mean, SEM) were significantly (p &lt; 0.05) higher in the second (178 ± 8) and third (171 ± 6) decades than in the fourth (158 ± 4) or fifth (140 ± 12) decades, and were inversely correlated with age (r = -0.39, p = 0.0006), diminishing at a rate of 1.3 mg/ml (0.73%) per year. Radial cortical bone density levels (grams per square centimeter) were similar in the third (0.711 ± 0.021), fourth (0.721 ± 0.012), and fifth (0.736 ± 0.012) decades and were not related to age (r = 0.17, p = 0.39).
We conclude that vertebral trabecular bone loss in women commences during or prior to the third decade. In contrast, radial cortical bone density does not decline during the premenopausal years.
Bone mineral density in australia compared with the united states
Authors: Pocock Nicholas A. , Dr. Eisman John A. , Mazess Richard B. , Sambrook Philip N. , Yeates Michael G. , Freund Judith 
Published: February 2010

Abstract
Bone density measurements are currently being performed throughout the world in the diagnosis and management of osteoporosis as well as in research into this major health problem. However, it is not clear to what extent bone mineral density (BMD) values determined by dual-photon absorptiometry at one center can be applied to another. This is particularly relevant for the quantitative comparison of results from studies carried out in different laboratories. Furthermore, many centers now acquiring densitometers may not have the resources to determine their own normal range, relying instead on a “normal” range provided by the manufacturer. The question of the comparability of BMD data obtained in different centers was examined by comparing the normal range for the lumbar spine and proximal femur in 203 normal white Australian women and 892 normal white U.S. women, obtained using the same model densitometer.
The two populations were compared according to decade. From superimposition of the Australian individual values on the North American normal ranges, only minor differences between the two populations were seen at any of the sites measured at any decade. None of these minor differences were statistically significant.
This study shows a close similarity between BMD values in both the proximal femur and lumbar spine in normal white women in Australia and North America, provided the same model densitometer is used. Thus data obtained from different centers in populations with similar ethnic composition may be compared directly. These findings provide for the first time a sound basis for the quantitative comparison of the at times conflicting studies carried out in widely differing settings around the world.
Bone-resorbing agents promote and interferon-γ inhibits bone cell collagenase production
Authors: Shen Victor , Kohler Gail , Jeffrey John J. , Peck William A. 
Published: February 2010

Abstract
Parathyroid hormone, prostaglandin E2, 1α,25-dihydroxyvitamin D3, interleukin-1, tumor necrosis factor α, and epidermal growth factor, all known stimulators of bone resorption, markedly enhanced collagenase secretion by rat fetus osteoblastlike cells in primary culture as judged by enzyme-linked immunosorbent assay. Untreated cells contained no immunostainable or extractable collagenase. Collagenase was detected in the treated cells and media only after 1–3 h of treatment, and there was no increment in collagenase activity when cells were treated in the presence of actinomycin D or cycloheximide. Cells secreted collagenase in a latent form and also elaborated collagenase inhibitor; chromatographic separation of collagenase from collagenase inhibitor and subsequent activation of the collagenase with trypsin yielded the active species in stimulated but not in unstimulated cells. The ability of individual prostanoids, among seven tested, to promote collagenase production correlated positively with their reported capacity to promote bone resorption. Interferon-γ (IFN-γ), a known resorption inhibitor, blocked the increment in collagenase production caused by all agents tested. These results indicate a close linkage between stimulation of bone resorption and collagenase production by osteoblastlike cells. Various resorption stimulators, including some not previously tested for effects on collagenase, augment the de novo synthesis and secretion of collagenase and act by an IFN-γ-inhibitable mechanism.