bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forskolin has both stimulatory and inhibitory effects on bone resorption in fetal rat long bone cultures
Authors: Dr. Lorenzo Joseph A. , Sousa Sandra , Quinton Joy 
Published: February 2010

AbstractThe diterpene forskolin which increases 3′,5′-cyclic adenosine monophosphate concentrations (cAMP) in intact cells by directly activating the enzyme adenyl cyclase, was examined for its ability to alter bone resorption in fetal rat long bone cultures. After 48 h, forskolin inhibited resorption at 1.0 and 10 μ However, after 120 h, it had a small stimulatory effect at 1.0 μM and no net effect on resorption at 10 μ Isobutylmethylxanthine (IBMX), which elevates cAMP levels in cells by inhibiting the enzyme 3′,5′-cyclic adenosine monophosphate phosphodiesterase, produced a resorptive response which was slightly different from that of forskolin. After both 48 and 120 h, IBMX at 0.1 mM stimulated resorption while at 1.0 mM, it had only inhibitory effects. In bones which were stimulated to resorb with either parathyroid hormone or 1,25(OH)2 vitamin D, forskolin inhibited resorption. The inhibitory effects of forskolin on hormonally stimulated resorption were transient in cultures treated with 1.0 μM but were sustained with 10 μM. Inhibitory responses to forskolin did not appear to result from toxicity since they were completely reversed when forskolin was removed from the media.These results imply that agents which increases 3′,5′-cyclic adenosine monophosphate concentrations in bone activate two resorptive pathways: one which is inhibitory and another which is stimulatory.
Secretion and metabolism of monomeric human calcitonin: Effects of age, sex, and thyroid damage
Authors: Tiegs Robert D. , Body Jean Jacques , Barta Joyce M. , Dr. Heath Hunter 
Published: February 2010

Abstract
Some data suggest that human calcitonin (CT) secretion is lower in women than in men, decreases with age and the menopause, and is absent in thyroidectomized persons. To further explore CT secretory physiology, we have studied basal and calcium-stimulated plasma immunoreactive CT (iCT) and silica-extractable monomeric CT concentrations in 148 healthy volunteers and 33 patients with a history of thyroid damage (total or subtotal thyroidectomy, radioiodine treatment for thyrotoxicosis). Both whole-plasma iCT and extractable CT levels were lower basally and after calcium infusion in women than in men, basal levels being reduced about 50% and calcium-stimulated values about 75% from those of male subjects. There were no significant changes in basal iCT or extractable CT concentrations with age, and CT secretory capacity (CT response to calcium infusion) likewise did not change with age. Infusion of monomeric CT to constant concentration in 27 persons permitted estimates of CT metabolic clearance rates (MCRs) and secretion rates (SRs). Calculated MCRs of about 9 ml/min · kg−1 (persons aged 21–30 yr) and 6 ml/min · kg−1 (persons aged 54–70 yr) were in good agreement with published data, and did not differ between the sexes. SRs were dependent upon the assay method used to estimate basal plasma CT concentrations, being highest when whole-plasma iCT values were used. Based on estimates of plasma monomeric CT from the silica extraction procedure, the SR of CT was 59 ± 6 (SE) ng/d · kg−1 in men, and 22 ± 3 ng/d · kg−1 in women. Thyroid damage reduced, but did not abolish, apparent CT immunoreactivity, even in silica extracts of plasma. However, all subsets of thyroiddamaged patients had absent-to-markedly-impaired CT secretion in response to calcium infusion. We conclude that CT secretion is substantially lower both basally and after stimulation in women than in men, and that this difference in CT immunoreactivity probably reflects differences in circulating CT bioactivity. The sex difference in plasma CT concentrations probably results from lower rates of CT secretion in women, not increased MCR. There is no age-related decrease of plasma CT concentrations (or CT secretory reserve), calling into question the concept that a progressive deficiency of CT is partly resonsible for age-related (“senile”) osteoporosis. Surgical or radiation damage to the thyroid gland commonly abolishes C-cell response to calcium; such CT-deficient patients form a population suitable for determining whether or not reduced CT secretion can impair skeletal homeostasis.
Cytochemical bioassay of circulating concentrations of rat parathyroid hormone: Application to a study of age and sex
Authors: Dr. Peng Tai-Chan , Garner Sanford C. , Hirsch Philip F. , Posillico James T. 
Published: February 2010

Abstract
We have found that the cytochemical bioassay (CBA) method, originally developed to measure circulating levels of biologically active parathyroid hormone (bioPTH) in humans, also can measure endogenous concentrations of PTH in rats. Therefore, we have applied this assay method to examine the relationships between age and sex and the circulating levels of bioPTH, calcium, and phosphorus in Fischer rats. The concentration of bioPTH increased in both males and females from 5 to 15 months of age (p &lt; .001) with no significant sex-related difference. Mean bioPTH values ranged from 2.3 to 3.6 pg (human PTH equivalents)/ml; these values were much lower (1 to 2 orders-of-magnitude) than those reported by others who used radioimmunoassays for PTH that do not discriminate between biologically active and inert PTH fragments. The CBA values for bioPTH were also 1/4–1/5 those obtained in rat serum by newer, more sensitive methods, the N-terminal specific PTH radioimmunoassay and the bioassay based on stimulation of chick renal adenylate cyclase.
Regression analysis did not reveal any significant correlation between serum calcium and age. However, serum inorganic phosphorus decreased significantly (p &lt; .001) from 5 to 15 months of age in both male and female rats and was much lower in females than in males (p &lt; .001). The fall in serum phosphorus was negatively correlated with the rise in bioPTH (p &lt; .001).
This study, the first to our knowledge to use a CBA to detect physiological changes in the circulating levels of bioPTH in rats, demonstrates the usefulness of the assay in experiments in this species.
The effect of oral phosphate administration on major indices of skeletal metabolism in normal subjects
Authors: Silverberg Shonni J. , Shane Elizabeth , Clemens Thomas L. , Dempster David W. , Segre Gino V. , Lindsay Robert , Dr. Bilezikian John P. 
Published: February 2010

Abstract
The effect of brief periods of phosphate administration on indices of human skeletal metabolism was investigated. Thirteen subjects (8 women, 5 men; 19–36 years old) received 2 g of oral phosphate daily for 5 days. Serum phosphorus rose 26% (3.8 ± 0.1 mg/dl to 4.8 ± 0.1 mg/dl; p &lt; .01) while total calcium fell (9.3 ± 0.1 mg/dl to 8.9 ± 0.1 mg/dl; p &lt; .01). Parathyroid hormone levels increased by 50% (14.1 ± 2.0 pg/ml to 21.5 ± 1.7 pg/ml; p &lt; .05) although values remained within the normal range. A persistent phosphaturia (0.64 ± 0.10 g/g Cr to 1.8 ± 0.4 g/g Cr; p &lt; .05) and a 69% fall in urinary calcium (80.8 ± 10.0 mg/g Cr to 24.6 ± 6.0 mg/g Cr; p &lt; .001) were observed. 1,25-dihydroxyvitamin D3 and urinary hydroxyproline concentrations did not change significantly but the bone γ-carboxyglutamic acid protein (BGP) concentration rose 41% by day 2 (9.6 ± 1.3 mg/ml to 13.5 ± 2.2 mg/ml; p &lt; .005) and remained elevated throughout the study period. These results support the possibility that brief periods of phosphate administration may be useful in the therapy of disorders associated with low bone turnover, such as osteoporosis.
The solid, calcium-phosphate mineral phases in embryonic chick bone characterized by high-voltage electron diffraction
Authors: Dr. Lee Dosuk D. , Landis William J. , Glimcher Melvin J. 
Published: February 2010

Abstract
The solid mineral phases of calcium-phosphate (Ca-P) in the long bones from embryonic chicks between the ages of 9 and 13 days have been examined by high voltage (1.0 MV) electron microscopy and electron micro-diffraction. The study was undertaken to identify the chemical and crystallographic nature of the inorganic mineral phase(s) prepared under conditions which significantly reduce artifacts of specimen preparation and microscopic examination of the tissues.
Electron microdiffraction patterns of solid mineral phase particles in the osteoid matrices of the subperiosteal region of tibiae were principally those of poorly crystalline hydroxyapatite. In rare instances (less than 1% of the estimated volume of the mineral phase present in the zone of early mineralization), relatively large single crystals were observed within clusters of hydroxyapatite. From calculations of both interplanar spacings and measurements of angular displacement of diffraction reflections from single crystal microdiffraction patterns, two distinct phases other than hydroxyapatite were identified: brushite and β-tricalcium phosphate. A third phase, resembling an apatite, remains unidentified. The results suggest that very small amounts of nonapatitic phases of Ca-P exist in chicken bone tissue. No temporal relationship could be established between the nonapatitic and apatitic phases. There is at present no evidence from this study to support the concept that nonapatitic phases are precursors of a final apatitic phase in bone.
Production of and response to growth-stimulating activity in isolated bone cells
Authors: Wong Glenda L. , Roberts R. , Miller E. 
Published: February 2010

Abstract
Autologous growth-promoting activity has been shown to be secreted by bone organ cultures. To identify the cellular source of these growth factors, we have studied the activity present in cell extracts prepared from isolated bone cells released early or late from mouse calvariae following collagenase digestion. Previous studies have established that early released cell populations reside on the bone surface and consist of a heterogeneous mixture of cells that are less osteoblastic than late released cells. We find that soluble extracts of the latter cells contain more growth-promoting activity/mg of cellular protein than those of the former. By this criterion late released cells appear to be the major source of endogenous growth factors. On the other hand, upon exposure to bone cell-derived cell extracts, early released cells express a greater-fold increase in [3H]-thymidine incorporation into acid insoluble radioactivity than late released osteoblasts because of the high basal mitogenic activity of the latter which may be related to their production of autologous growth factor. These data suggest that both early and later released cells may be major targets for bone growth factors produced in situ by late released osteoblasts.
Chicken osteoclasts do not possess calcitonin receptors
Authors: Nicholson G.C. , Moseley J.M. , Sexton P.M. , Prof. Martin T.J. 
Published: February 2010

Abstract
Osteoclasts freshly isolated from embryonic chicks have been examined for calcitonin receptors using radio-iodine-labeled salmon calcitonin. Calcitonin binding to chick osteoclasts could not be shown by either autoradiography or biochemical binding studies. Furthermore, calcitonin did not stimulate cyclic AMP production. By contrast, rat osteoclasts have abundant calcitonin receptors, and a sensitive cyclic AMP response to calcitonin has been shown previously. It is concluded that chick osteoclasts do not possess calcitonin receptors, a finding which could explain the lack of calcitonin responsiveness observed in other avian osteoclast culture systems.
Demonstration that ethanol inhibits bone matrix synthesis and mineralization in the rat
Authors: Turner Russell T. , Greene Virginia S. , Bell Norman H. 
Published: February 2010

AbstractThe effects of ethanol on bone and mineral metabolism were investigated in 3 groups of male rats. The first group received ethanol administered as 36% of caloric content in a liquid diet for 3 weeks. A second group of pair-fed animals was given the same liquid diet, except that sucrose was substituted isocalorically for ethanol. A third group of rats was fed standard laboratory chow. The ethanol-treated rats gained significantly less weight than laboratory chow-fed controls but gained the same weight as the pair-fed animals. Ethanol-treated rats had a modest but significant decrease in mean serum calcium compared to pair-fed controls (10.3 ± 0.1 vs. 10.6 ± 0.1 mg/dl, p &lt; .001). Mean serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone were the same in the 3 groups. The ethanol-treated animals showed significant decreases in mean tibial length (1.88 ± 0.01 vs. 1.98 ± 0.02 cm, p &lt; .01), mean endosteal bone formation rate (0.0006 ± 0.0001 vs. 0.0026 ± 0.0003 mm3/day, p &lt; .001) and mean periosteal bone formation rate (0.022 ± 0.001 vs. 0.026 ± 0.001 mm3/day, p &lt; .01) compared to the pair-fed controls. The ethanol-treated rats demonstrated significant decreases in mean periosteal mineralization rate (7.5 ± 0.3 vs. 10.3 ± 0.6 μm/day, p &lt; .01) and mean periosteal apposition rate (8.5 ± 0.5 vs. 11.0 ± 0.8 μm/day, p &lt; .05) and a significant increase in mean periosteal osteoid thickness (15.5 ± 1.4 vs. 10.4 ± 0.8 μm, p &lt; .01) compared to pair-fed controls. The laboratory chow-fed controls had higher mean endosteal bone formation rate (0.0040 ± 0.0004 mm3/day, p &lt; .01), mean periosteal bone formation rate (0.034 ± 0.001 mm3/day, p &lt; .01), mean periosteal mineralization rate (12.5 ± 0.7 μm/day, p &lt; .01) and mean periosteal apposition rate (13.0 ± 0.7 μm/day, p &lt; .01) than the pair-fed control animals. The results are interpreted to mean that in the rat ethanol alters mineral homeostasis and diminishes formation of bone matrix and mineralization of osseous tissue. These effects cannot be accounted for by alterations in the metabolism of vitamin D. Further, caloric restriction and inhibition of growth themselves diminish formation of bone matrix and mineralization of osseous tissue.
Effect of bisphosphonates on proliferation and viability of mouse bone marrow-derived macrophages
Authors: Dr. Cecchini Marco G. , Felix Rolf , Fleisch Herbert , Cooper Philip H. 
Published: February 2010

Abstract
Bisphosphonates (BP) are powerful inhibitors of bone resorption. Their mechanism of action, although still unclear, is now believed to be at the cellular level. In this study we investigated the effects of these compounds on proliferation, induced either by L-cell conditioned medium (CSF-1) or 4-phorbol 12-myristate 13-acetate (PMA) of bone marrow cells (BMC) and on CSF-1-induced proliferation and viability of bone marrow derived macrophages (BMDMΦ). BMC proliferation, measured by [3H]-TdR incorporation or by clonal assay in soft agar, was significantly inhibited by 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP) and 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP) at 2.5 × 10−7M and by dichloromethylenebisphosphonate (Cl2MBP) at 2.5 × 10−6M. This inhibitory effect was also confirmed on the proliferation, measured by [3H]-TdR incorporation, of BMDMΦ. In the absence of CSF-1, the viability of this latter cell population, estimated by DNA content per well and lactate dehydrogenase (LDH) released into the medium, was affected in the following order of concentrations: Cl2MBP, 1.0 × 10−4M; AHBuBP, 5.0 × 10−5M; and AHPrBP, 2.5 × 10−5M. Since osteoclasts and macrophages might share a common early progenitor cell, probably under the control of CSF-1, the effect exerted by BP on the proliferation of the macrophage precursors may also be extended to the osteoclast precursors.
1α,25-Dihydroxyvitamin D3 receptors in human thymic and tonsillar lymphocytes
Authors: Provvedini Diego M. , Rulot Christine M. , Sobol Robert E. , Tsoukas Constantine D. , Dr. Manolagas Stavros C. 
Published: February 2010

Abstract
In vitro activated human peripheral blood lymphocytes possess the receptor protein for 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study we have examined whether activated lymphocytes that occur in vivo in human thymuses and tonsils also possess receptors for 1,25(OH)2D3. Freshly isolated lymphocyte preparations, from five separate surgical specimens of thymus and tonsil, were depleted of monocytes and examined, before and after fractionation on a density gradient of Percoll, for [3H] 1,25(OH)2D3 binding by means of sucrose density gradient sedimentation, by saturation analysis of the binding, and by DNA-cellulose chromatography. The state of activation of the lymphocyte preparations was determined using [3H] thymidine incorporation, DNA and RNA quantitation (using acridine orange), and by determining the presence or absence of markers of activation (interleukin-2 receptor, transferrin receptor, and HLA-DR molecules). In both the thymic and the tonsillar lymphocyte preparations we detected a 1,25(OH)2D3-binding molecule possessing sedimentation coefficient of 3.3 S and dissociation constant of 10−10M as well as DNA binding capability. In thymic lymphocytes, the 1,25(OH)2D3 receptor concentration correlated positively with the number of lymphocytes expressing the transferrin receptor (r = 0.84; p &lt; 0.05). In addition, in both thymic and tonsillar lymphocytes the concentration of 1,25(OH)2D3 receptors correlated positively with the number of cells in the G1a phase of the cell cycle (r = 0.79, p &lt; 0.01, and r = 0.88, p &lt; 0.001 for thymic and tonsillar lymphocytes, respectively). In contrast, the 1,25(OH)2D3 receptor concentration in these preparations did not correlate with the rate of cell proliferation. These results indicate that thymic and tonsillar lymphocytes in the early stages of activation possess in vivo the 1,25(OH)2D3 receptor protein, and suggest that 1,25(OH)2D3 may act in vivo on these cells.
Aminohexane diphosphonate in the treatment of paget' s disease of bone
Authors: Atkins Roger M. , Yates Ashley J.P. , Gray Richard E.S. , Urwin Graeme H. , Hamdy Neveen A.T. , Beneton Monique N.C. , Rosini Sergio , Dr. Kanis John A. 
Published: February 2010

Abstract
We studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long-term control of Paget's disease.
Osteoclast-like cell formation in fetal and newborn long-term baboon marrow cultures is more sensitive to 1,25-dihydroxyvitamin D3 than adult long-term marrow cultures
Authors: Takahashi N. , Mundy G.R. , Kuehl T.J. , Roodman G.David 
Published: February 2010

Abstract
It is unknown if osteoclasts derived from animals at different developmental stages differ. To study this question, we used a long-term baboon marrow culture system in which osteoclast-like multinucleated cells (MNC) are formed. Fetal, newborn, or adult baboon marrow cultures were tested to determine if they differ in their responsiveness to osteotropic hormones. In fetal and newborn marrow cultures 1,25-dihydroxyvitamin D3 (1,25D3) at 10−10M significantly increased MNC formation with a maximal effect seen at 10−9M. Higher concentrations of 1,25D3 progressively decreased MNC formation. In contrast, in adult baboon marrow cultures, 10−9M 1,25D3 was required to significantly increase MNC formation, with a maximal affect at 10−8M 1,25D3. Calcitonin (25–200 ng/ml) inhibited MNC formation in fetal, newborn, or adult baboon marrow cultures treated with 1,25D3 in an identical manner. The effects of 1,25D3 on granulocyte-macrophage progenitor cells (CFU-GM), the probable precursors of MNC, were identical in fetal and adult baboon marrow cultures, with a significant inhibition of CFU-GM colony formation at 10−8M 1,25D3. These results suggest that 1) osteoclast precursors are more sensitive to some osteotropic hormones during the fetal and newborn periods, and 2) differences in the 1,25D3 sensitivity of osteoclast-like MNC formation in fetal, newborn, and adult baboon marrow cultures are not due to effects on early proliferating precursors but may result from effects of 1,25D3 on fusion of later precursors for MNC.
Relaxation of rat gastrointestinal smooth muscle by parathyroid hormone
Authors: Mok Lester L.S. , Cooper Cary W. , Thompson James C. 
Published: February 2010

AbstractIn this study we investigated whether parathyroid hormone (PTH) can produce relaxation of gastrointestinal (GI) smooth muscle as it has been reported to do for vascular and uterine smooth muscle. Muscle tissue preparations from rat stomach, duodenum, ileum, or colon were mounted in a 37°C tissue bath and perfused with oxygenated medium. Changes in isometric tension were recorded with a force-displacement transducer connected to a polygraph. Decreases in either resting tension or agonist-induced tension (0.5–1.0 μ M acetylcholine or carbachol) were observed within 1–2 min of PTH addition and were reversible upon removal of the peptide. All GI regions tested were responsive to PTH. Synthetic rPTH-(1–34) (0.1–100 nM) produced a dose-dependent relaxation of both fundic (ED50 = 5.2 nM) and colonic (ED50 = 2.5 nM) muscle strips. At 100 nM, a 90% decrease in fundic tension and a 70% decrease in colonic tension were seen. At 100 nM, bPTH-(1–34), but not bPTH-(7–34) or rat calcitonin gene-related peptide, also was effective in relaxing fundic or colonic muscle. Similarly, in the fundic muscle, 500 nM bPTH-(3–34) alone was ineffective, but it inhibited the effect of 5 nM rPTH-(1–34) when both peptides were tested in combination. Likewise, 100 nM bPTH-(3–34) also inhibited the relaxation induced by 5, 10, or 100 nM bPTH-(1–34). The results show PTH to be highly effective in nanomolar concentrations in causing relaxation of GI smooth muscle. The findings suggests that rat GI smooth muscle possesses receptors for PTH and indicate a potential role for PTH or PTH-related peptides in GI motility.
Evidence that pulsed electromagnetic fields inhibit coupling of adenylate cyclase by parathyroid hormone in bone cells
Authors: Cain Christopher D. , Adey W. Ross , Luben Richard A. 
Published: February 2010

Abstract
To investigate the biochemical effects of pulsed electromagnetic fields (PEMF) on bone in particular and on cell membrane-associated activity in general, we have studied the modification by PEMF of cAMP metabolism in primary calvarial bone cells. We report that PEMF inhibited cAMP accumulation stimulated by bovine PTH(1–34) peptide. After a 1-hr PEMF exposure, the cAMP response to PTH (2–7 min) was decreased in exposed cells to 48–70% (p &lt; 0.05) of the response of unexposed cells; furthermore, this inhibition disappeared after 10–20 min with PTH. This inhibition occurred at submaximal PTH doses (2.4–7.3 nM) and no effect was observed at maximal PTH doses (24 nM). Thus with PEMF, the dose response curve for PTH became 0.5 log unit less sensitive. PEMF did not affect the cAMP response to cholera toxin and forskolin. However, when submaximal doses of both forskolin (0.5–1.0 μM) and PTH (0.24–2.4 nM) were used, forskolin prevented inhibition of cAMP production by PEMF in the range of fields and stimulus epochs which normally inhibit cAMP production.
It is proposed that PEMF inhibits PTH-stimulated coupling of the adenylate cyclase system and that this inhibition does not affect the intrinsic activity of the G-protein and the catalytic subunit.