bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of podosomes in osteoclasts cultured on bone laminae: Effect of retinol
Authors: Zambonin-Zallone Alberta , Teti Anna , Carano Aldo , Marchisio Pier Carlo 
Published: February 2010

Abstract
Osteoclasts, isolated and purified from the medullary bone of calcium-deficient egg-laying hens, adhere to glass coverslips in vitro by means of specialized protrusions of the ventral membrane, denoted podosomes. These structures represent dotlike close-contact adhesion sites in which most cytoskeletal proteins involved in linking the plasma membrane to microfilaments are organized according to a specific and previously described pattern also shared by many oncogene-transformed cells. We show now that podosomes are not only a feature of osteoclasts adhering to artificial glass surfaces but are also present in the ventral membrane of osteoclasts adhering to bone laminae. Moreover, the quantity and the topography of podosomes may be modulated by retinol, which increases bone-resorbing activity of osteoclasts both in vivo and in vitro. A comparative transmission electron microscopy study of osteoclasts adhering on bone laminae in vitro or in vivo indicates that podosomes with identical features are present in the clear zone of the osteoclasts in either condition. Since podosomes are the sealing structures of the clear zone, podosome formation may represent one of the modifications involved in the reorganization process of the osteoclast that precedes bone resorption.
Effects of cisplatin on parathyroid hormone- and human lung tumor-induced bone resorption
Authors: Abramson Edith C. , Chang Jeffry , Mayer Marjorie , Kukla Lawrence J. , Shevrin Daniel H. , Lad Thomas E. , Buschman Robert , Kukreja Subhash C. 
Published: February 2010

Abstract
We have previously shown that dichlorodiamine platinum (DDP), or cisplatin, a cancer chemotherapeutic agent, is effective in the treatment of malignancy-associated hypercalcemia. In the present studies, we evaluated its effects on bovine parathyroid hormone (PTH)- or tumor-induced bone resorption in vitro in the neonatal mouse calvarial bone resorption assay. PTH alone or tumor extract (TE) of a human squamous cell lung cancer alone caused a significant increase in the bone resorption and in the number of osteoclasts in the calvaria. The addition of 3 and 10 μg/ml DDP inhibited the PTH- or TE-induced bone resorption. Lower doses of 1 and 2 μg/ml DDP, although not effective in inhibiting the PTH-induced bone resorption, were effective in lowering the TE-induced bone resorption. The number of osteoclasts was also reduced by DDP treatment. We therefore conclude that DDP is effective in the treatment of malignancy-associated hypercalcemia by virtue of its inhibitory effects on osteoclast numbers and on bone resorption.
Skeletal contribution of cyclic adenosine monophosphate in response to parathyroid hormone and calcitonin in vivo in the rat
Authors: Dr. Morrison Nancy E. , Ramanathan Subramanyam , Suh Se Mo 
Published: February 2010

Abstract
Cyclic adenosine monophosphate (cAMP) is thought to be a second messenger for the actions of both parathyroid hormone (PTH) and calcitonin (CT). We examined the release of cAMP from rat bone in vivo after administration of synthetic rat PTH-(1–34) (rPTH), synthetic human PTH-(1–34) (hPTH), or synthetic human CT (hCT). Blood from the venous effluent of the femoral bone of rats (bone blood) was drawn at 5 and 10 minutes after the administration of hormones. The cAMP content of the bone blood was then compared to the cAMP content of arterial blood. In both kidney-clamped and non-kidney-clamped rats, hCT led to a significantly greater concentration of cAMP in the bone blood than in the arterial blood. We interpret this to be due to bone production and release of cAMP. Neither hPTH nor rPTH produced a significantly greater amount of cAMP in the bone blood than in arterial blood. These data do not preclude the possibility that there was a production of cAMP within the bone tissue itself after PTH but suggest that there was no release of cAMP from the bone into the bone blood.
Direct transformation from quiescence to bone formation in the adult periosteum following a single brief period of bone loading
Authors: Pead Matthew J. , Skerry Timothy M. , Dr. Lanyon Lance E. 
Published: February 2010

Abstract
The concept of resorption preceding formation in a coupled response is well established as the normal sequence of remodeling in adult bone. So prevalent is this concept, however, that the idea of the direct activation of osteogenic modeling in normal adult bone is often ignored. This experiment documents the direct transformation of the normal, quiescent, adult periosteum to active bone formation. The osteogenic stimulus was provided by a single short period of dynamic loading. Periosteal activation and the production of new bone within 5 days of loading was unaccompanied by resorption or the presence of osteoclasts. We therefore conclude that an adult resting periosteum can become directly converted to formation as a physiologic response to an appropriate osteogenic stimulus without the need for resorption. To distinguish this process from remodeling we suggest it be called renewed modeling. It is notable that a single short exposure to an “osteogenic” loading regime can influence the full cascade of cellular events between quiescence and active bone formation.
Elevated calcium, phosphorus, and magnesium retention in pregnant rats prior to the onset of fetal skeletal mineralization
Authors: Brommage Robert , Baxter Daniel C. 
Published: February 2010

Abstract
Intestinal absorption and renal excretion rates of Ca, P, and Mg were compared in pregnant and control virgin rats fed a purified diet containing 0.55% Ca, 0.54% P, and 0.067% Mg. Four consecutive balance intervals of 5 days each were examined, beginning on day 1 of gestation. During days 6–10 of gestation, pregnant rats had elevated fractional intestinal absorptions of Ca (29.6 ± 1.7 versus 20.6 ± 1.5%), P (65.4 ± 2.0 versus 59.9 ± 0.9%), and Mg (54.3 ± 1.5 versus 42.4 ± 2.6%). Since urinary excretions of these elements did not change, the pregnant rats retained more Ca, P, and Mg than virgin rats. Fractional intestinal absorptions of these elements during pregnancy were similar to control values during days 1–5 and 11–15 of gestation and then rose for each element during days 16–20 of gestation. Presumably because of an increase in glomerular filtration rate, urinary excretions of Ca and Mg were elevated by 40 and 26% during days 16–20 of gestation. In contrast, urinary P excretion was decreased by 30% during days 11–20 of gestation. Analyses of uterine mineral contents indicated the increased maternal Ca and Mg retentions during pregnancy were balanced by the transfers of these elements to the fetuses. In contrast, pregnancy was associated with a net maternal retention of P. These data are consistent with previous observations of increased maternal skeletal mineralization during early pregnancy before the onset of fetal osteogenesis and subsequent enhanced maternal Ca intestinal absorption concurrent with fetal skeletal mineralization.
Determinants of peak trabecular bone density in women: The role of androgens, estrogen, and exercise
Authors: Buchanan James R. , Myers Cathleen , Lloyd Tom , Leuenberger Paula , Demers Laurence M. 
Published: February 2010

Abstract
To elucidate determinants of peak trabecular bone density, we studied the role of androgens, estrogen, and aerobic exercise in 30 women from 18 to 22 years old. The women were divided into three groups: Sedentary, 11 normal women who did not exercise regularly; eumenorrheic, 10 athletes with normal menstrual function; and oligomenorrheic, 9 athletes with exercise-induced oligomenorrhea. All athletes participated in aerobic sports that did not involve selective resistance loading of the back. Serum free and albumin-bound testosterone (fab T), androstenedione (A), and estradiol (E2) were measured on four separate occasions at consecutive 7 day intervals and averaged. Trabecular density was measured by quantitative computed tomography of the lumbar spine.
Peak trabecular bone density was related to fab T (r = 0.48, p = 0.007), A (r = 0.40, p = 0.03), and E2 (r = 0.40, p = 0.04). When taken in combination, androgens and estrogen each accounted independently for significant portions of the variance in bone density [fab T and E2 (R2 = 0.38, p = 0.002) and A and E2 (R2 = 0.27, p = 0.01)]. Bone density (mg/ml, mean ± standard error of the mean, SEM) in the sedentary group (174 ± 6) was not significantly different from that in the eumenorrheic (183 ± 12, p = 0.47) or oligomenorrheic (161 ± 11, p = 0.32) subjects.
We conclude that androgens and estrogen function as independent and additive determinants of peak trabecular bone density in young women. The quantitative impact of aerobic exercise (without resistance loading) and exercise-induced menstrual dysfunction appears to be less important than that of the hormones.
Tetrapyrroles as inhibitors of normal cartilage metabolism: Relative potency of different compounds
Authors: Vassilopoulou-Sellin Rena , Oyedeji Caroline O. 
Published: February 2010

AbstractThe present study was designed to explore the role of different tetrapyrroles as inhibitors of cartilage metabolism. We studied the effects of tetrapyrroles on the incorporation of [35S]sulfate into proteoglycans, [14C]-leucine into protein, and [3H]uridine into the RNA of normal cartilage from two different vertebrate classes using the embryonic chicken pelvic rudiment bioassy and the hypophysectomized rat costal cartilage bioassay, both very sensitive to cartilage growth factors and growth inhibitors. We compared the relative potencies of the following compounds: both metalloporphyrins (heme and chlorophyllin), linear tetrapyrroles (bilirubin), and heme proteins (hemoglobin, myoglobin, and cytochrome c). Hemoglobin and heme were the most potent inhibitors of rat cartilage metabolism, and bilirubin was a far more potent inhibitor of embryonic chick cartilage metabolism. Chlorophyllin had moderate inhibitory activity, especially on chick cartilage, whereas cytochrome c was inactive in these bioassays. Surprisingly, myoglobin was relatively ineffective despite its close similarity to heme and hemoglobin. The bilirubin-induced inhibition of sulfate incorporation into chick cartilage was partially prevented when glutathione was included in the incubation medium, suggesting that a free-radical mechanism may be involved. There were significant differences in the sensitivity of the two cartilages studied, indicating there may be species-dependent sensitivity to different tetrapyrroles.
Glucocorticoids increase parathyroid hormone receptors in rat osteoblastic osteosarcoma cells (ROS 17/2)
Authors: Yamamoto Itsuo , Potts John T. , Segre Gino V. 
Published: February 2010

Abstract
The effects of glucocorticoids on parathyroid hormone (PTH) receptors was studied using rat osteosarcoma-derived cells (ROS 17/2), which have an osteoblastic phenotype, and [125I][Nle8, Nle18, Tyr34]bovine(b)PTH-(1–34)amide as the radioligand. Treatment of cells with physiologic concentrations of hydrocortisone resulted in a time and dose-dependent increase in PTH binding. The increase in PTH binding could be observed by 10 h of exposure to hydrocortisone (2 × 10−7 M), was maximally enhanced by 48 h, and was maintained for the subsequent 7 days of continuous exposure to the steroid. With removal of hydrocortisone, PTH receptor binding promptly returned toward control levels. The increase in PTH binding was attributed to an increase in the availability of receptor binding sites, not to altered receptor binding affinity, and was blocked by cycloheximide. PTH-stimulated adenylate cyclase was also enhanced by glucocorticoids, and a close correlation was observed between PTH binding and PTH-stimulated adenylate cyclase. However, hydrocortisone not only increased PTH binding but also enhanced the efficiency of postreceptor signaling: 5′-guanylimidodiphosphate [Gpp(NH)p]- and forskolin-stimulated adenylate cyclase activities were also increased. Thus, enhanced PTH stimulation of adenylate cyclase by glucocorticoids resulted from at least two effects—increased receptor availability and enhanced postreceptor efficiency of transmembranous signaling.
Characterization of insulin binding in the UMR-106 rat osteoblastic osteosarcoma cell
Authors: Ituarte Eloy A. , Ituarte Hector G. , Iida-Klein Akiko , Hahn Theodore J. 
Published: February 2010

Abstract
The correlation of insulin receptor occupancy with classic insulin effects, such as stimulation of glucose uptake, have not been examined in osteoblastlike cells. Accordingly, we characterized insulin binding and examined its relationship to stimulation of glucose analog transport in the UMR-106 rat osteoblastic osteosarcoma cell line. Insulin binding in UMR-106 cells was found to be pH sensitive, temperature dependent, saturable, and specific. Proinsulin was 100-fold less effective than insulin in displacing specific [125I]insulin binding in these cells, whereas IGF-I at concentrations between 0.1 and 10 nM produced no displacement of [125I]insulin but did produce significant displacement of insulin binding at 100 and 1000 nM. Insulin receptor downregulation was observed after exposure to 100 nM insulin for 6 h at 37°C and was temperature dependent. Insulin binding was reversible after 24 h at 4°C. Insulin binding correlated directly with stimulation of 2-deoxyglucose uptake at insulin concentrations between 0.1 and 100 nM, with a half-maximal concentration (ED50) of 0.9 nM for both [125I]insulin binding displacement and stimulation of 2-deoxyglucose uptake. Hence, there was no evidence for spare insulin receptors with regard to stimulation of glucose analog transport. Scatchard analysis of insulin binding kinetics yielded a curvilinear plot, suggesting negative cooperativity. Analysis of insulin binding kinetics using a two-site model yielded a KD of 0.9 nM for the apparent high-affinity binding site and an estimated 80,000 high-affinity binding sites per cell. These findings demonstrate that osteoblastlike cells exhibit a relationship between insulin binding and glucose transport stimulation that is similar to that in liver cells and other insulin-sensitive tissues. The UMR-106 cell line therefore appears to represent a useful system for studies of the regulation of insulin binding and action in an osteoblastic cell.
Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro
Authors: Pfeilschifter Johannes , Chenu Chantal , Bird Andrew , Mundy Gregory R. , Roodman David G. 
Published: February 2010

Abstract
Interleukin-1 (IL-1) α and β and tumor necrosis factor (TNF) α and β are potent stimulators of bone resorption in vitro and in vivo. However, the mechanisms underlying this increased bone resorption have not been clearly defined. Increased bone resorption can result from increased activity of individual osteoclasts, increased numbers of osteoclasts, or both. Therefore, we have used a long-term human marrow culture system that forms multinucleated cells (MNC) with the characteristics of osteoclasts to examine the effects of IL-1 and TNF on osteoclast formation. Human recombinant IL-1α and IL-1β and human recombinant TNF-α and TNF-β stimulated MNC formation from 4- to 60-fold. IL-1α, IL-1β, TNF-α, and TNF-β significantly increased MNC formation at very low concentrations: 2.5 × 10−13 M for IL-1α and IL-1β, 10−11 M for TNF-α, and 10−10 M for TNF-β In addition, these cytokines enhanced MNC formation in the presence of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], a potent osteotropic factor that stimulates MNC formation by stimulating fusion of mononuclear precursor cells. Simultaneous addition of IL-1 and TNF to the cultures resulted in a synergistic stimulation of MNC formation. These results suggest that: (1) IL-1 and TNF stimulate bone resorption in part by increasing osteoclast formation and (2) an extremely low concentration of these factors can synergistically increase osteoclast formation in the absence of other factors, such as 1,25-(OH)2D3. These data suggest that synergistic interactions among cytokines play an important role in maintaining bone cell activity in normal and pathologic states.
Cyclic therapy of osteoporosis with neutral phosphate and brief, high-dose pulses of etidronate
Authors: Mallette Lawrence E. , Leblanc Adrian D. , Pool James L. , Mechanick Jeffrey I. 
Published: February 2010

Abstract
We have designed a cyclic regimen for the treatment of osteoporosis based on the activate, depress, free, and repeat (ADFR) concept. Osteoclastic bone resorption is activated by 7 days of oral neutral phosphate and inhibited with a brief pulse (5 days) of etidronate disodium at a high dose (20 mg/kg body weight). Patients next take calcium supplements for 48 days before resuming phosphate to enter the next cycle. Osteoporotic women increased the bone mineral density of the lumbar spine at 6 months by 7.2 ± 5.2% (mean ± SD, N = 14) and at 12 months by 8.2 ± 4.0% (N = 8). Control observations in regularly exercising postmenopausal women (N = 30) showed no significant change in spine mineral density after 20 months (0.5 ± 3.2%), confirming the stability of the measurement technique. The two patients who responded poorly to the cyclic regimen each showed a blunted rise in serum PTH during oral phosphate administration, suggesting that the rise in PTH induced by oral phosphate may be an important component of this cyclic regimen. This preliminary study does not identify which component or components of the regimen are responsible for the increase in bone mass but provides positive encouragement for randomized studies designed to determine the optimum dosage, duration, and timing of each component of the regimen.
Transforming growth factor β modulates proliferation of osteoblastic cells: Relation to its effect on receptor levels for epidermal growth factor
Authors: Uneno Susumu , Dr. Yamamoto Itsuo , Yamamuro Takao , Okumura Hideo , Ohta Shuichi , Lee Kaechoong , Kasai Ryuichi , Konishi Junji 
Published: February 2010

Abstract
The effect of transforming growth factor β (TGF-β) on cellular proliferation of osteoblastic MC3T3-E1 cells was studied with particular emphasis on its effect on modulation of epidermal growth factor (EGF) receptors. In other cells, TGF-β has been reported to augment EGF receptors. Exposure of MC3T3-E1 cells to TGF-β initially increased cell surface EGF receptor levels and decreased the rate of DNA synthesis. The initial elevation of EGF receptor levels was due to increased receptor number per cell, not to changes in binding affinity. On the contrary, prolonged exposure (longer than 40 h) resulted in a decrease in EGF receptor and an increase in the rate of DNA synthesis. Thus, the effects of TGF-β on these cells appears to be biphasic, reflecting complex mechanisms of action; the early effects of TGF-β may be consistent with cellular differentiation to the osteoblastic phenotype with decreased cellular proliferation, whereas chronic exposure of these cells to TGF-β stimulated cellular proliferation and inhibited osteoblastic phenotype expression. It is not likely that stimulation of cellular proliferation was through elevation of EGF receptor levels, because TGF-β did not enhance the stimulatory effect of EGF on cellular proliferation. Thus, we conclude that TGF-β possesses a stimulatory effect on the cellular proliferation of osteoblastic MC3T3-E1 cells independent of its modulative effect on EGF receptor level.
Quantification of bone mineral content using dual-photon absorptiometry in a normal Japanese population
Authors: Hagiwara Satoshi , Miki Takami , Nishizawa Yoshiki , Ochi Hironobu , Onoyama Yasuto , Morii Hirotoshi 
Published: February 2010

Abstract
The bone mineral content of lumbar spine and/or total body were quantified in 217 healthy Japanese (86 males and 131 females) using a Dichromatic Bone Densitometer (Norland Corp., Model 2600). The bone mineral density of the third lumbar vertebra (L3 BMD) decreased significantly after age 20 in males (r = -0.417, p &lt; 0.0002), with acceleration of the decrease after age 50 (r = -0.621, p &lt; 0.00002). A significant correlation was found between L3 BMD and age after age 40 (r = -0.747, p &lt; 0.00001) in females. L3 BMD correlated with both the body height (r = 0.335, p &lt; 0.0001) and the body weight (r = 0.340, p &lt; 0.0001). Total bone mineral content from the second to fourth lumbar vertebrae correlated significantly with total body bone mineral (r = 0.880, p &lt; 0.00001) in these normal subjects. Lumbar spine bone mineral as measured by dual-photon absorptiometry is lower in Japan than the bone mass in the United States, although not lower than in other parts of the world.
Plasma carriers influence the uptake of cholecalciferol by human hepatoma-derived cells
Authors: Haddad John G. , Aden David P. , Aw T. Choon 
Published: February 2010

Abstract
The uptake of [3H]cholecalciferol by the human hepatoma-derived cell lines Hep G2 and Hep 3B was examined as a function of the sterol's presentation on various plasma proteins at their native concentrations. Control cultures utilized devitalized cells cross-linked with glutaraldehyde and estimated nonspecific sterol adherence to cells. With both cell lines, neither albumin nor plasma vitamin D binding protein permitted cholecalciferol uptake above control values. With Hep G2 cells, only low-density lipoprotein presentation of the sterol resulted in significant cellular uptake that had features resembling a receptor-mediated process. With Hep 3B, only high-density lipoprotein presentation of the sterol resulted in a significant uptake that was cell, carrier, and time dependent. These results support the hypothesis that lipoprotein carriers could account for the efficient hepatic accumulation of cholecalciferol in vivo.
Bone resorption by isolated human osteoclasts in vitro: Effects of calcitonin
Authors: Murrills Richard J. , Shane Elizabeth , Lindsay Robert , Dr. Dempster David W. 
Published: February 2010

Abstract
Human osteoclasts were isolated from 12- to 17-week-old fetal tissue and from transiliac crest bone biopsies for an in vitro study of their biology. A hypodermic needle was used to flush either the fetal long bones or the trabeculae of the iliac crest bone biopsy with tissue culture medium and the resulting cell suspension sedimented briefly either onto the surface of plastic tissue culture dishes, for time-lapse microcinematography, or onto slices of devitalized bovine cortical bone for quantitative assay of bone resorption. The osteoclasts were motile, tartrate-resistant acid phosphatase positive and capable of excavating pits in slices of devitalized bovine cortical bone. Human calcitonin, at doses of 1 ng/ml and 1 μg/ml, caused a 70% inhibition of bone resorption by human fetal osteoclasts over a 24 h period but had no apparent effect on the morphology or motility of either fetal or adult osteoclasts.
Effects of calcitonin gene-related peptide on cyclic AMP formation in chicken, rat, and mouse bone cells
Authors: Michelangeli V. P. , Fletcher A. E. , Allan E. H. , Nicholson G. C. , Martin T. J. 
Published: February 2010

Abstract
Mixed bone cell cultures obtained by sequential collagenase-trypsin digestion of newborn chick, rat, and mouse calvaria responded to calcitonin gene-related peptide (CGRP) with a dose-dependent increase in cyclic AMP formation. The amplitude of response to CGRP in each species was less than that to parathyroid hormone (PTH). The CGRP effect was not the result of an action as a weak calcitonin agonist, since in most instances a calcitonin effect was not observed. Only in early digests of mouse calvarial cells were consistent stimulatory effects of calcitonin on cyclic AMP noted, and these were always considerably less in amplitude than those to CGRP. It is concluded that chick, rat, and mouse bones contain cells in osteoblast-rich populations that respond specifically to CGRP with a rise in cyclic AMP.