bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of ipriflavone and its metabolites on a clonal osteoblastic cell line
Authors: Benvenuti Susanna , Tanini Annalisa , Frediani Uliana , Bianchi Sandro , Masi Laura , Casano Rosaria , Bufalino Lidia , Serio Mario , Dr. Brandi Maria Luisa 
Published: February 2010

Abstract
Protective effects of ipriflavone, an isoflavone derivative, in osteoporosis are believed to be caused by the inhibitory action on bone resorption. A direct effect of ipriflavone on bone formation is as yet unknown. Ipriflavone and four of its metabolites (I, II, III, and V) were examined for their effects on parathyroid hormone response, collagen synthesis, alkaline phosphatase activity, and cell proliferation in a clonal cell population of rat osteoblastic cells. Pretreatment of osteoblasts with high concentrations of ipriflavone for 48 h significantly inhibited the cAMP response to parathyroid hormone, producing a shift in the dose-response curve; at lower concentrations metabolites II and III potentiated the cAMP accumulation induced by low doses of parathyroid hormone. The 48 h treatment with metabolite V at the 1 nM dose significantly stimulated collagen synthesis in osteoblastic cells. Ipriflavone and metabolite I showed a biphasic stimulatory action on the alkaline phosphatase activity of osteoblasts, with a maximal effect at the 0.1 and 1 nM doses, respectively. A similar biphasic response was observed with ipriflavone and metabolite I on osteoblastic cell growth, with a maximal effect at the 0.1 nM concentration. These results suggest a direct role of ipriflavone in modulating the synthetic and growth properties of osteoblast-like cells.
Effects of potassium peroxydiphosphate on bone resorption
Authors: Gaffar Abdul , Alander Cynthia B. , Head Raisz Lawrence G. 
Published: February 2010

Abstract
Potassium peroxydiphosphate (KPDP) is a slowly hydrolyzed pyrophosphate analog that can release hydrogen peroxide during hydrolysis. We tested its effects on the resorption of cultured fetal rat long bones as measured by the release of previously incorporated 45Ca, both by direct addition of KPDP to the medium and after preincubation of KPDP with large-molecular-weight resorbing factors followed by dialysis to reduce the KPDP concentration. With direct addition, KPDP at a concentration of 1 mM could inhibit the resortive response to bacterial lipopolysaccharide (LPS), parathyroid hormone (PTH), prostaglandin E2 (PGE2), and mouse recombinant interleukin-1 (mrIL-1). The response to LPS was partially inhibited at 0.3 mM KPDP. Control resorption in the absence of stimulators was also inhibited. Potassium pyrophosphate at 1 mM was less effective as an inhibitor of bone resorption. The inhibitory effects of KPDP did not appear to be due entirely to nonspecific toxicity since partial recovery occurred after it was removed. There was no significant decrease in [3H]thymidine or [3H]proline incorporation into bones incubated with KPDP at 1 mM for 5 days, but [3H]proline incorporation was decreased at 24 h, suggesting that KPDP may have a general inhibitory effect on bone cells. When media with and without stimulators of resorption were incubated overnight at 4°C with KPDP at 5.8 mM and then dialyzed to bring the concentration to below 0.3 mM, the bone-resorbing activity of PTH, LPS, and mrIL-1 was completely lost. This may have been due to the slow release of hydrogen peroxide; however, preincubation with equimolar concentrations of H2O3 caused only partial inactivation of PTH and LPS. Finally, 3% KPDP applied topically in hamsters reduced alveolar bone resorption, indicating that it could interact directly with local pathogenetic factors in vivo. These results indicate that KPDP may be a useful inhibitor of bone resorption. High concentrations of KPDP are required, but it is biodegradable to the normal body constituents, K+ and HPO42-.
Inhibition of bone resorption by a monoclonal antibody that reacts with a 150 kD membrane protein in chicken osteoclasts
Authors: Hentunen Teuvo A. , Lakkakorpi Päivi T. , Rautiala Timo , Väänanen H. Kalervo 
Published: February 2010

Abstract
Bone resorption is a multistep process that includes the maturation of osteoclast precursors, the special attachment of fully differentiated osteoclasts to mineralized bone surface, and the dissolution of inorganic mineral, as well as the breakdown of organic matrix. We have produced a large panel of monoclonal antibodies directed against chicken osteoclasts to obtain specific probes for studying the function of osteoclasts. One of our antibodies, K20, inhibited bone resorption of isolated osteoclasts almost completely. Several pieces of evidence suggested that the antigen detected by this antibody was located in the plasma membrane of the osteoclast. In western blot analysis K20 antibody specifically recognized a 150 kD protein in the medullary bone microsome fraction under reducing and nonreducing conditions. In addition to osteoclasts and some bone and bone marrow mononuclear cells, a positive immunoreaction was seen in the kidney tubules. These data suggest that monoclonal antibody K20 reacts with an osteoclast surface antigen that is functionally important in bone resorption.
Gallium nitrate inhibits bone resorption and collagen synthesis in neonatal mouse calvariae
Authors: Lakatos Peter , Mong Seymour , Stern Paula H. 
Published: February 2010

AbstractGallium nitrate (GN) is an agent used in the treatment of hypercalcemia. To more fully characterize the direct actions of GN on bone, we examined its effects on medium calcium, medium β-glucuronidase (β-GLU), and collagen synthesis in control and hormone-stimulated neonatal (4–6 days) mouse calvariae in vitro. GN (10 μg/ml) inhibited parathyroid hormone-stimulated (PTH; 1 nM) calcium release. A 24 h preincubation with 10 μg/ml of GN was required for complete inhibition; partial inhibition was seen with 12 h preincubation; 1, 3, or 6 h was inadequate. A dose-response study showed that with 24 h preincubation, 5, 3, and 1 μg/ml of GN inhibited 81, 62, and 0% of PTH-induced calcium release. The effects of GN on the release of β-GLU generally paralleled those on the release of calcium except that 10 μg/ml of GN stimulated β-GLU release. Collagen synthesis was inhibited 50% by 3 μg/ml of GN, whereas noncollagen protein synthesis was unaffected. With PTH + GN no further decrease was observed. When GN was withdrawn from the medium after 24 h of preincubation, the inhibitory effect on calcium release and β-GLU activity, but not on collagen synthesis, persisted through the 72 h of culture. GN also inhibited the resorption elicited by thyroxine (1 μM) and interleukin-1β (10 nM) but not by 1,25-dihydroxyvitamin D3 (30 pM). Our results indicate that GN is a powerful inhibitor of bone resorption in neonatal mouse calvariae even at low doses. A preexposure time is required to induce the persistent effect, but the continuous presence of GN is not necessary to maintain its effects on bone. Although GN has a primary cellular site of action, the requirement for preculture could suggest that GN could, in addition, make the bone matrix more resistant to resorption.
Salmon stanniocalcin and bovine parathyroid hormone have dissimilar actions on mammalian bone
Authors: Dr. Stern Paula H. , Shankar Geetha , Fargher Robert C. , Copp D. Harold , Milliken Christine E. , Sato Kanji J. , Goltzman David , Herrmann-Erlee M.P.M. 
Published: February 2010

Abstract
Stanniocalcin (STC), a calcium-regulating glycoprotein hormone isolated from the corpuscles of Stannius of salmon, was tested for effects on bone and calcium metabolism in mammalian species (rats and mice). STC generally failed to alter serum calcium of parathyroidectomized rats at concentrations equimolar with effective concentrations of parathyroid hormone (PTH). STC did not increase cAMP in ROS 17/2.8 or UMR-108 osteosarcoma cells, OK kidney cells, fetal rat limb bones, or neonatal mouse calvariae, and similarly failed to increase urinary cAMP in rats. STC did not consistently stimulate resorption in any of the rodent bone culture systems, although variable resorptive responses were elicited in fetal mouse calvariae. The results indicate that this fish hormone has limited, if any, PTH-like activity on calcium metabolism in mammalian systems.
Structural and composition studies on the mineral of newly formed dental enamel: A chemical, X-ray diffraction, and 31p and proton nuclear magnetic resonance study
Authors: Bonar Laurence C. , Shimizu Masaharu , Roberts James E. , Griffin Robert G. , Glimcher Melvin J. 
Published: February 2010

Abstract
The present report describes a study of the development and maturation of the mineral component of dental enamel. We prepared porcine enamel of different stages of maturation, from the very immature enamel of unerupted teeth, with a mineral content of 45%, to fully mature enamel, with a mineral content of ∼99%. We fractionated the less mature enamel by density centrifugation and examined the enamel density fractions and unfractionated enamel by a variety of chemical and physical techniques, including conventional and radial distribution function x-ray diffraction analysis, conventional and Fourier transform infrared spectroscopy, 31P and 1H nuclear magnetic resonance spectroscopy, and chemical analysis. The three most immature preparations, from unerupted teeth, had mineral contents of 45, 67, and 91 and Ca/P molar ratios of 1.41, 1.44, and 1.47. Density distribution histograms of the three fractions show that the early maturation of dental enamel mineral is accompanied by an increase in tissue density, reflecting the increase in mineral content. The density distribution in each sample is relatively narrow, indicating that the maturation process occurs at a fairly homogeneous rate, with all enamel in an anatomically defined zone mineralizing to about the same extent. X-ray diffraction studies indicate that even the least mature, least mineralized of these immature samples is considerably more crystalline than the most mature bone mineral studied and that crystalline perfection of the enamel crystals increases further with maturation. Both the a and c axes of the mineral unit cell expand significantly during early stages of maturation. Solid-state 31P nuclear magnetic resonance spectroscopy studies indicate that dental enamel contains a DCPD-like HPO4 component in an apatitic lattice, similar to the component previously observed in bone and some synthetic calcium phosphates. The proportion of this DCPD-like component decreases with maturation but is readily detectable even in fully mature enamel. The infrared spectroscopic studies indicate that the 3570 cm−1 band ascribed to the OH− group of the hydroxyapatite crystals is absent in the least mature enamel but can be detected and becomes progressively stronger as the enamel becomes more mature. The increase in the content of the OH− groups of the apatite crystals is concomitant with the observed increase in unit cell parameters. Similar studies on very young and very old mature bone of four different species failed to detect the presence of OH− groups.
Preventive effects of clomiphene citrate on estrogen-deficiency osteopenia elicited by LHRH agonist administration in the rat
Authors: Dr. Goulding Ailsa , Fisher Lorryn 
Published: February 2010

Abstract
The estrogen agonist and antagonist clomiphene citrate has been shown to prevent bone loss induced by ovariectomy in the rat. In young women estrogen-deficiency bone loss is a clinical problem associated with the use of luteinizing hormone releasing hormone (LHRH) agonists, such as buserelin, to treat endometriosis. The aim of this study was to determine whether clomiphene citrate (10 mg/kg body weight per week orally) would prevent the osteopenic effect of buserelin (25 μg/kg body weight per day SC) in the rat. Four groups of animals with 45Ca-labeled skeletons were studied for 4 weeks: group A, placebo controls; group B, buserelin; group C, clomiphene; and group D, buserelin + clomiphene. Bone resorption was monitored by measuring the urinary excretion of 45Ca and hydroxyproline. Clomiphene slowed bone breakdown and inhibited the osteopenic effect of buserelin. Total-body calcium values (mean ± SD) were (mg) 2635 ± 181, 2267 ± 85, 2566 ± 126, and 2624 ± 77 in groups A to D, respectively. Osteopenia was present only in group B (P &lt; 0.001). Interestingly buserelin lowered blood 17β-estradiol and uterine weights to a similar extent in the presence and absence of clomiphene. Because clomiphene inhibited estrogen-deficiency bone loss in buserelin-treated rats without depressing the hypoestrogenic action of this LHRH agonist, it is suggested that the use of clomiphene to protect the skeleton during LHRH agonist therapy of endometriosis warrants further study.
X-ray microanalysis of fluoride distribution in microfracture calluses in cancellous iliac bone from osteoporotic patients treated with fluoride and untreated
Authors: Boivin Georges , Grousson Brigitte , Meunier Pierre J. 
Published: February 2010

Abstract
Fluoride is able to augment cancellous bone mass in vertebral osteoporosis but is responsible for osteoarticular side effects in which microfractures are thought to be involved. During healing of these microfractures, a callus is formed all around the cancellous fracture line. Our hypothesis is that in fluoride-treated osteoporotic patients, calluses are bone sites where fluoride is focally deposited at a high concentration, and this could induce a local defect of calcification with a poor healing of microfractures. Our aim was to validate this hypothesis on several calluses following microfractures in undecalcified iliac cancellous bone from six women with osteoporosis (four fluoride treated and two untreated). Histologically normal iliac cancellous bone tissue, taken from a subject having neither fluoride treatment nor microfracture, was also examined. Selected areas, including new woven bone (calluses) and old lamellar bone, were carbon-coated and analyzed using an electron microprobe. Fluoride Kα and calcium Kα radiations were detected with wavelength and energy-dispersive spectrometers, respectively. In old lamellar bone at a distance from microfractures, the fluoride level was similar in normal and untreated osteoporotic patients but was slightly increased in treated osteoporotic patients. In untreated osteoporotic patients, the fluoride level was slightly higher (about 1.2 times) at the site of microfractures (lamellar and woven bone) than in lamellar bone far from such fractures, but fluoride was homogeneously distributed in lamellar and woven bone. In contrast, in treated osteoporotic patients, fluoride content was much higher (about 1.7 times) at the site of microfractures (lamellar and woven bone) than in lamellar bone far from fractures, but fluoride was heterogeneously distributed within the calluses, with the highest level in woven bone and the smallest in adjacent lamellar bone. The present data demonstrate that fluoride is preferentially concentrated in calluses of cancellous microfractures in fluoride-treated osteoporotic patients. It is likely but remains to be proven that this focal increase in fluoride uptake compromises the healing of microfractures.
Modulation of PTH-stimulated osteoclastic resorption by bisphosphonates in fetal mouse bone explants
Authors: Dr. van der Pluijm Gabri , Löwik Clemens W.G.M. , de Groot Henny , Alblas Marcel J. , van der Wee-Pals Lianne J. A. , Bijvoet OLAV L. M. , Papapoulos Socrates E. 
Published: February 2010

Abstract
We examined the effects of the bisphosphonates Cl2MDP, APD, and Me2APD on osteoclastic resorption in the absence and presence of PTH using fetal mouse osteoclast-free bone explants cocultured with fetal liver as a source of osteoclast precursors. Results revealed qualitative and quantitative differencs among the bisphosphonates tested. With Cl2MDP and APD fractional inhibition of resorption (measured as 45Ca release) in the presence of PTH was proportional to that obtained in its absence. In contrast, Me2APD, which is the most potent inhibitor of the three, was found at low concentrations (≤5 × 10−7 M) to enhance the PTH-stimulated osteoclastic resorption. APD as well, at concentrations that could not inhibit resorption, had a similar effect, but Cl2MDP did not. These studies describe a new phenomenon, that low doses of nitrogen-containing bisphosphonates can act synergistically with PTH and enhance osteoclastic resorption. These findings may have clinical implications in the management of patients with increased osteoclastic resorption due to parathyroid overactivity.
Stimulation by parathyroid hormone-related protein and transforming growth factor-α of phosphate transport in osteoblast-like cells
Authors: Pizurki Lara , Rizzoli René , Caverzasio Joseph , Bonjour Jean-Philippe 
Published: February 2010

Abstract
Parathyroid hormone (1–34) [PTH-(1–34)] has been shown to stimulate sodium-dependent phosphate transport (NaPiT) in UMR-106 osteoblast-like cells through a cAMP-dependent mechanism. Whether a synthetic amino-terminal fragment of parathyroid hormone-related protein (PTHrP) or the full-length molecule, which are recognized to interact with the same receptor as PTH, affect NaPiT in the same way is not known. We investigated and compared the effects of bPTH-(1–34), PTHrP-(1–34), and PTHrP-(1–141) on NaPiT and cAMP production in the osteoblastic cell line UMR-106. Each of the three peptides increased cAMP production and exerted a concentration-dependent stimulation of NaPiT after incubation for 4–6 h. We also studied the effect of transforming growth factor-α (TGF-α), which is another tumoral product secreted by certain hypercalcemia-associated tumors, on NaPiT and the TGF-α-induced modulation of the response to PTHrP or PTH. TGF-α caused a 30% stimulation of NaPiT, which remained stable from 6 to 24 h, by a cAMP-independent mechanism. In contrast, TGF-α attenuated cAMP production stimulated by PTH, PTHrP-(1–34), or PTHrP-(1–141). PTHrP or PTH did not further increase NaPiT in TGF-α-treated cells. These results indicate that NaPiT, a possibly important function of osteoblastic cells, was similarly affected by PTH and PTHrP. TGF-α increased NaPiT and modulated in a similar way the effects of both PTH and PTHrP.
1α,25-Dihydroxyvitamin D3 rapidly increases cytosolic calcium in clonal rat osteosarcoma cells lacking the vitamin D Receptor
Authors: Baran Daniel T. , Sorensen Ann Marie , Shalhoub Victoria , Owen Thomas , Oberdorf Annette , Stein Gary , Lian Jane 
Published: February 2010

Abstract
1α,25-Dihydroxyvitamin D3 [1α,25-(OH)2D3] rapidly increases cytosolic calcium in a variety of cell types. Although these rapid effects do not appear to directly involve genome activation, the requirement for the classic vitamin D receptor is unclear. Clonal rat osteosarcoma cells, ROS 17/2.8, respond to 1α,25-(OH)2D3 with an increase in osteocalcin message but ROS 24/1 cells do not. The lack of the receptor for vitamin D in the ROS 24/1 cells has been confirmed by the absence of any detectable vitamin D-receptor complex binding to the vitamin D-responsive element (VDRE) of the osteocalcin gene and the absence of vitamin D receptor mRNA in the cells. Quin-2-loaded ROS 17/2.8 and ROS 24/1 cells were treated with 1α,25-(OH)2D3 in the presence and absence of extracellular calcium and with the inactive epimer, 1β,25-dihydroxyvitamin D3 [1β,25-(OH)2D3]. The 1α,25-(OH)2D3 increased cytosolic calcium in the ROS 17/2.8 and 24/1 cells after 5 minutes in a dose-responsive manner and in the presence and absence of extracellular calcium. Pretreatment of both cell lines with 1β,25-(OH)2D3 for 30 s blocked the hormone-induced rise in cytosolic calcium. The rapid effects of 1α,25-(OH)2D3 on ROS cells with and without the vitamin D receptor and the ability of the inactive epimer to inhibit these effects indicate that the signaling system mediating the hormone's rapid actions is not the classic vitamin D receptor.
Pamidronate Reduces PTH-mediated bone loss in a gene transfer model of hyperparathyroidism in rats
Authors: Mitlak Bruce H. , Rodda Christine P. , von Deck Mercedes D. , Dobrolet Nancy C. , Neer Robert M. , Dr. Nussbaum Samuel R. 
Published: February 2010

Abstract
We Evaluated Spinal And Femoral Bone Mass And Density Utilizing Dual-Energy X-Ray Absorptiometry (Dexa) In Rats In Which Severe Hyperparathyroidism Was Produced By The Expression Of The Gene For Human Pth-(1–84) (Hpth). This Gene Was Incorporated Into A Retroviral Vector That Was Transfected Into Fibroblasts Which Were Subsequently Injected Into Their Peritoneal Cavities. Further, We Examined The Effect Of The Administration Of Pamidronate On Bone Mass And Density In The Presence Of Extremely High Concentrations Of Hpth. Three Groups Of Rats Were Studied. Groups 1 And 2 Receive The Hpth-Secreting Fibroblasts; Group 2 Subsequently Received Pamidronate (2.5 Mg/Kg Iv) 18 And 27 Days After Receiving The Fibroblasts. These Animals Developed Levels Of Hpth &gt; 1.0 μg/Liter And Became Hypercalcemia Within 20 Days. These Animals Became Lethargic And Were Significantly Lower In Weight Than Age-Matched Controls (Group 3, P &lt; 0.05). After Accounting For The Animal Weight There Was A Further Significant Decrease In Bone Mineral Content And Density (Bmc And Bmd) On Day 29 Attributable To Hpth-Mediated Bone Loss. Treatment With Pamidronate Resulted In A Higher Bmc Of The Lumbar Spine Than In The Untreated Animals, With Elevated Concentrations Of Hpth. The Bmd Was Significantly Higher At Both The Lumbar Spine And Femur In The Pamidronate-Treated Animals (P &lt; 0.05). The Cv Of Paired Measurements Of Bmd Was 2.7% At The Spine And 1.5% Of A Femur, Respectively. The Bmc Of The Lumbar Spine And Femur Was Closely Correlated With The Ashed Weight Of The Same Bones (R = 0.92 And 0.85, Respectively).
A new method for measuring cancellous bone erosion depth: Application to the cellular mechanisms of bone loss in postmenopausal osteoporosis
Authors: Cohen-Solal Martine E. , Shih Mei-Shu , Lundy Mark W. , Dr. Parfitt Michael A. 
Published: February 2010

Abstract
We have devised a new method for measurement of final depth of erosion in cancellous bone with an intra-individual precision of 4.3% and applied it to determine the mechanism of continuing reduction in trabecular thickness after menopause. Mean erosion depth (SD) was 40.8 (2.0) μm in 10 healthy postmenopausal women and 41.4 (2.1) μm in 10 age-matched patients with postmenopausal osteoporosis; the difference was not statistically significant. In contrast, wall thickness, using a method based on density differences between new and old bone, was 39.5 (2.0) μm in the normal subjects and 35.3 (2.0) μm in the patients with osteoporosis (p &lt; 0.0001). The balance per remodeling cycle (ΔBMU) was −1.34 (2.49) μm in the normal subjects and −6.11 (1.95) μm in the patients with osteoporosis. This difference was also highly significant (p &lt; 0.001). Indirect estimations of erosion depth and ΔBMU, based on the fall in trabecular thickness from an assumed premenopausal value of 147 μm and the number of remodeling cycles accumulated since menopause, agreed closely with the measured values. Erosion depth measured by the Eriksen method also showed no significant difference between the two groups, but because the values were substantially higher ΔBMU was improbably high in both groups, did not differ significantly between groups, and was inconsistent with the observed difference in trabecular thickness. We conclude that (1) the more rapid continuing loss of cancellous bone in patients with postmenopausal osteoporosis than in age-matched control subjects is due entirely to a difference in wall thickness, not to a difference in erosion depth; and (2) defective recruitment and/or function of osteoblasts is the major cellular mechanism of trabecular thinning in patients with postmenopausal osteoporosis and probably also in normal subjects. We emphasize that these conclusions do not speak to the mechanism of complete removal of trabeculae in the early years after menopause.