bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anomalies in the Measurement of Changes in Total-Body Bone Mineral by Dual-Energy X-Ray Absorptiometry During Weight Change
Authors: Tothill P. , Hannan W. J. , Cowen S. , Freeman C. P. 
Published: April 2006

Abstract
For an eating disorder study over a period of 1 year, we measured total-body bone mineral using a Hologic QDR 1000W in a total of 157 subjects and observed anomalies that questioned the accuracy of such measurements. Using the recommended Enhanced software, a change in total bone mineral content (ΔBMC) correlated positively with a change in weight (ΔW; r = 0.66), but a loss of weight was associated with an increase in bone mineral areal density (BMD; r = 0.58), arising from a reduction in bone area (AREA). Both regressions were highly significant. The dominant factor in this relationship was a strong correlation between ΔAREA and ΔBMC, for all parts of the skeleton, r &gt; 0.9, with a slope close to 1. This is implausible because bone area would not be expected to change. When Standard software was used, the slope of the ΔBMC/ΔW correlation was steeper, but the ΔBMD/ΔW regression became positive. An artefact of dual-energy X-ray absorptiometry processing was suspected, and phantom measurements were made. The phantom consisted of tissue-equivalent hardboard cut and stacked to form cylinders corresponding to the head, trunk, arms, and legs of a standard man. The skeleton was constructed from layers of aluminium sheet as an approximation of the average shape, BMD, BMC, and AREA in each region. When aluminium thickness was varied, BMD thresholds were found, approximately 0.4 g/cm2 for the legs and 0.2 g/cm2 for the arms. Above these, bone area rose fairly rapidly toward a plateau. At higher skeletal densities, the relationships between measured and true BMDs were close to linear, but slopes were less than unity, so that changes would be underestimated by 10–30%. Increases of thickness of the soft tissue of the phantom lowered AREA slightly. Uniform fat proportion increases led to decreases in BMC and AREA, but lard wrapped in an annulus around the limbs led to spurious increases in BMC and AREA of a similar magnitude to those observed in vivo, while BMD fell slightly, although there had been no true change of bone variables. Similar results were obtained with lard around the limbs of a volunteer. Reanalysis of phantom scans using Standard software confirmed the software differences noted in vivo. The phantom measurements offer an explanation of the anomaly in vivo and demonstrate that, under different circumstances, change in both BMC and BMD can be wrongly recorded. We believe that no valid conclusions can be drawn from measurements by the Holgic QDR 1000W of bone changes during weight change.
Bone Mass and Hip Axis Length in Healthy Asian, Black, Hispanic, and White American Youths
Authors: Wang May-Choo , Aguirre Melissa , Bhudhikanok Grace S. , Kendall Carmen G. , Kirsch Susannah , Marcus Robert , Bachrach Laura K. 
Published: April 2006

Abstract
The primary objective of this study was to examine the associations of ethnicity, diet (calcium, protein, energy), and weight-bearing activity with dual-energy X-ray absorptiometry (DXA)-measured bone mass and hip axis length (HAL) in 423 Asians, blacks, Hispanics, and non-Hispanic Caucasians, aged 9–25 years. Bone mass was expressed as bone mineral content (BMC), bone mineral density (BMD), and bone mineral apparent density (BMAD). The data were analyzed using multiple linear regression, after stratifying for gender and pubertal stage and adjusting for height and weight. With few exceptions, Asians and Hispanics had comparable bone mass to whites at all pubertal stages. Greater femoral neck BMAD in black than white females was observed at all pubertal stages. Black males displayed greater BMD and BMAD than white males at all sites in early puberty and at the femoral neck in maturity. Calcium was positively and protein negatively related to BMAD at the femoral neck in early pubertal females. Among males, calcium was negatively associated with whole body BMC and BMD and spine BMD and BMAD in midpuberty. Weight-bearing activity was not associated with bone mass in females; in males, it was positively related only to femoral neck BMC in early puberty. There was an absence of evidence for ethnic differences in HAL among females. In males, we observed shorter HAL in mature Asians and blacks than whites. Neither diet nor activity was associated with HAL.
Pharmacological and Biochemical Evidence for the Regulation of Osteocalcin Secretion by Potassium Channels in Human Osteoblast-like MG–63 Cells
Authors: Moreau R. , Aubin R. , Lapointe J. Y. , Lajeunesse D. 
Published: April 2006

Abstract
Previous reports have suggested the involvement of voltage-activated calcium (Ca2+) channels in bone metabolism and in particular on the secretion of osteocalcin by osteoblast-like cells. 1 We now report that potassium (K+) channels can also modulate the secretion of osteocalcin by MG–63 cells, a human osteosarcoma cell line. When 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-treated MG–63 cells were depolarized by step increases of the extracellular K+ concentration ([K+]out) from 5–30 mM, osteocalcin (OC) secretion increased from a control value of 218 ± 13 to 369 ± 18 ng/mg of protein/48 h (p &lt; 0.005 by analysis of variance). In contrast, in the absence of 1,25(OH)2D3, there is no osteocalcin secretion nor any effect of cell depolarization on this activity. The depolarization-induced increase in 1,25(OH)2D3-dependent osteocalcin secretion was totally inhibited in the presence of 10 μM Nitrendipine (a Ca2+ channel blocker, p &lt; 0.005) without affecting cellular alkaline phosphatase nor cell growth. Charybdotoxin, a selective blocker of Ca2+-dependent K+ channels (maxi-K) present in MG–63 cells, 2 stimulated 1,25(OH)2D3-induced osteocalcin synthesis about 2-fold (p &lt; 0.005) after either 30, 60, or 120 minutes of treatment. However, Charybdotoxin was without effect on basal release of osteocalcin in the absence of 1,25(OH)2D3 pretreatment. Using patch clamp technique, we occasionally observed the presence of a small conductance K+ channel, compatible with an ATP-dependent K+ channel (GKATP) in nonstimulated cells, whereas multiple channel openings were observed when cells were treated with Diazoxide, a sulfonamide derivative which opens GKATP. Western blot analysis revealed the presence of the N-terminal peptide of GKATP in MG–63 cells, and its expression was regulated with the proliferation rate of these cells, maximal detection by Western blots being observed during the logarithmic phase of the cycle. Glipizide and Glybenclamide, selective sulfonylureas which can block GKATP, dose-dependently enhanced 1,25(OH)2D3-induced OC secretion (p &lt; 0.005). Reducing the extracellular calcium concentration with EGTA (μM range) totally inhibited the effect of Glipizide and Glybenclamide on osteocalcin secretion (p &lt; 0.005), which remained at the same levels as controls. Diazoxide totally prevented the effect of these sulfonylureas. These results suggest that voltage-activated Ca2+ channels triggered via cell depolarization can enhance 1,25(OH)2D3-induced OC release by MG–63 cells. In addition, OC secretion is increased by blocking two types of K+ channels: maxi-K channels, which normally hyperpolarize cells and close Ca2+ channels, and GKATP channels. The role of these channels is closely linked to the extracellular Ca2+ concentration.
Trabecular Bone Formation in the Healing of the Rodent Molar Tooth Extraction Socket
Authors: DeVlin H. , Hoyland J. , Newall J. F. , Ayad S. 
Published: April 2006

Abstract
The aim of this study was to investigate the nature of the template structure on which trabecular bone formation occurs during healing of the rodent tooth extraction socket, a well studied bone healing system. The presence of collagen type II mRNA has previously been described in the healing socket, although the formation of the protein or cartilage has not been observed. However, recent evidence from developmental and other bone healing studies indicates that collagen type III may be important in forming the preliminary scaffold on which bone trabeculae are formed. The maxillary right molar teeth were removed from rats under general anaesthesia and the animals killed at various times afterward. The tissues were examined using histological, in situ hybridization, and immunohistochemical staining techniques. It was concluded that collagen type IIA mRNA was produced by osteoblast cells of the socket, but that collagen type II, if present, would account for less than 0.01% of the total proteins extracted. During bone formation, Sharpey's fibers were seen radiating from the peripheral bone toward the center of the socket. These optically active collagen fibers were inserted into the forming bone trabeculae and were recognized by antibodies raised against collagen type III. The arrangement and composition of these fibers therefore suggest that they form a preliminary framework on which deposition of woven bone trabeculae occurs.
Effects of Thyroid Hormone Administration and Estrogen Deficiency on Bone Mass of Female Rats
Authors: Gouveia Cecilia H. A. , Jorgetti Vanda , Bianco Antonio C. 
Published: April 2006

Abstract
To investigate the effects of thyroxine (T4) administration on bone mass, five 81-day-old female rats were treated with T4 (25 μg of T4/100 g of body weight [bw]/day), and bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) 28 days later. The BMD values for the total skeleton, femoral, and tibial subsegments were lower than in controls (p ≤ 0.05). The lumbar spine (L2–L5) was not significantly affected by T4 treatment. Next, thirty-seven 211 ± 1.5 (mean ± SEM)-day-old female rats were divided into six groups as follows: (1) control; (2) ovariectomized (OVX); (3) 1xT4 (∼1.0 μg of T4/100 g of bw/day; approximately physiological replacement dose); (4) OVX+1xT4; (5) 2xT4 (∼2.0 μg of T4/100 g of bw/day); (6) OVX+2xT4. DXA scans were performed at days 0 and 85. Control rats showed a generalized BMD increase, as opposed to a decrease in OVX rats. The trabecular bone volume of the fifth lumbar vertebra was also lower in OVX rats than in controls (p &lt; 0.05). The 1xT4 treatment had no effect on BMD of intact rats, while treatment with 2xT4 impaired the expected BMD increase. Unexpectedly, the OVX+1xT4 group presented a generalized BMD increase that was significant for the total skeleton, L2–L5, and femoral subsegments (p &lt; 0.05), comparable to controls. Treating OVX animals with 2xT4 did not potentiate the osteopenic effects of estrogen deficiency, nor did it reverse the osteopenic effects of OVX. In conclusion, treatment with high doses of T4 caused BMD to decrease substantially, particularly at the femur, whereas near physiological doses of T4 prevented bone loss associated with OVX, and regardless of bone type (trabecular or cortical), the skeleton site seems to be a more important determinant of the effects of thyroid hormone on bone mass.
Bilateral Tibial Marrow Ablation in Rats Induces a Rapid Hypercalcemia Arising from Extratibial Bone Resorption Inhibitable by Methylprednisolone or Deflazacort
Authors: Magnuson Scott K. , Booth Randal , Porter Susan , Dr. Gorski Jeffrey P. 
Published: April 2006

Abstract
The goals of this study were to quantitate biochemical markers of bone metabolism on days 1–15 after bilateral tibial marrow ablation surgery in young adult rats and to determine the effect of a single dose of methylprednisolone (2 mg/kg) or deflazacort (2.5 mg/kg) given at the time of ablation. Unexpectedly, serum calcium levels rose to a maximum of 15.9 mg/dl on day 7 after marrow ablation and remained above normal through day 15. This increase was blocked by a single intramedullary injection of methylprednisolone or deflazacort immediately following ablation; however, the fact that both drugs produced a characteristic rapid 3- to 10-fold increase in the serum α2-macroglobulin level demonstrates that the drugs rapidly reached the circulation. Both methylprednisolone and deflazacort also inhibited intramedullary deposition of collagen by 40–60% on day 7, a time near which operated control animals achieved maximal accumulation of new bone in this model. Histological comparisons among the three experimental groups were largely consistent with biochemical results. The urinary hydroxyproline/creatinine ratio for the operated control group doubled on day 3 and then returned to presurgical levels on day 7 and later. The timing and size of the hydroxyproline/creatinine peak, as well as the fact that the intratibial osteoclastic response peaks on days 8–10 after ablation, suggests it results from extratibial bone resorption induced by marrow ablation. Consistent with this rationale, urinary calcium excretion in operated controls rose 9-fold from day 0 to day 3 and appeared to plateau over the period from day 3 to day 9, before returning to a near presurgical level on day 15. Elevated excretion of calcium noted on days 9–15 in deflazacort-treated animals, which occurs in the absence of a detectable increase in resorption marker hydroxyproline, may however be due to the known action of glucocorticoids in increasing kidney filtration of calcium. In summary, this is the first report to show that bilateral tibial marrow ablation in rats causes a rapid hypercalcemia and calciuria which is accompanied initially by a peak of bone resorption marker urinary hydroxyproline. We speculate that the source of calcium and hydroxyproline is extratibial osteoclastic bone resorption induced by circulating cytokines whose release from ablated tibias or osteoclastogenic action is inhibitable by methylprednisolone and deflazacort.
Different Responses of Bone Alkaline Phosphatase Isoforms During Recombinant Insulin-like Growth Factor-I (IGF-I) and During Growth Hormone Therapy in Adults with Growth Hormone Deficiency
Authors: Magnusson Per , Degerblad Marie , Sääf Maria , Larsson Lasse , Thorén Marja 
Published: April 2006

Abstract
We studied serum bone alkaline phosphatase (ALP) isoforms and other markers of bone turnover in growth hormone–deficient (GHD) adults (n = 22). The patients were followed during 1 week of insulin-like growth factor-I (IGF-I) administration, 40 μg/kg of body weight/day (n = 6), and during 24 months of growth hormone (GH) therapy, 0.125 IU/kg of body weight/week for the first month, and then 0.250 IU/kg of body weight/week (n = 20). Six ALP isoforms were separated and quantified by high-performance liquid chromatography: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. At baseline, the mean levels of B1, B2, and osteocalcin were higher in GHD adults than in healthy adults. After 1 week of IGF-I administration and 1 month of GH therapy, only B1 was decreased. We suggest that the initial decrease of B1 during GH therapy could be an effect of endocrine IGF-I action mediated by GH. After 3 months of GH therapy, both B1 and B2 increased as compared with placebo. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary pyridinoline cross-links/creatinine ratio increased during GH therapy. PICP increased significantly before bone ALP and osteocalcin, indicating an early stimulation of type I collagen synthesis as previously demonstrated by in vitro models. Different responses of the bone ALP isoforms during IGF-I and during GH therapy suggest different regulations in vivo.
Protein Interactions During Assembly of the Enamel Organic Extracellular Matrix
Authors: Paine Michael L. , Snead Malcolm L. 
Published: April 2006

Abstract
Enamel is the outermost covering of teeth and contains the largest hydroxyapatite crystallites formed in the vertebrate body. Enamel forms extracellularly through the ordered assembly of a protein scaffolding that regulates crystallite dimensions. The two most studied proteins of the enamel extracellular matrix (ECM) are amelogenin and tuftelin. The underlying mechanism for assembly of the proteins within the enamel extracellular matrix and the regulatory role of crystallite-protein interactions have proven elusive. We used the two-hybrid system to identify and define minimal protein domains responsible for supra molecular assembly of the enamel ECM. We show that amelogenin proteins self-assemble, and this self-assembly depends on the amino-terminal 42 residues interacting either directly or indirectly with a 17-residue domain in the carboxyl region. Amelogenin and tuftelin fail to interact with each other. Based upon this data, and advances in the field, a model for amelogenin assemblies that direct enamel biomineralization is presented.
Degradable Bisphosphonate-Alkaline Phosphatase-Complexed Hydroxyapatite Implants In Vitro
Authors: Dr. Denissen Harry , Van Beek Ermond , Van Den Bos Theo , De Blieck Jolanda , Klein Christel , Van Den Hooff Arnold 
Published: April 2006

Abstract
Degradable hydroxyapatite (HA) implants complexed with the resorption inhibiting agent bisphosphonate (PCP) and the mineralizing agent alkaline phosphatase (ALP) can theoretically maintain alveolar bone mass directly after extraction of teeth. The present in vitro study investigated the surface properties of PCP–ALP-complexed HA implants in relation to the requirements of implant behavior and action. Adsorbed PCP (pH 3.49) resulted in a flattening and broadening of the phosphate peaks and the formation of carbonate peaks in the HA pattern of the implant indicating a chemical alteration of the HA surface. Adsorption of ALP onto PCP-altered HA surfaces was 26% lower than onto HA implant blank surfaces. PCP–ALP-complexed HA implants released the PCP and ALP steadily and continuously over observation periods of, respectively, 75 and 14 days. During these observation periods, the ceramic grains of the HA implant became smaller and intergrain boundaries became broader. These morphologic characteristics suggested preconditioning of the HA implant surface for future bonding and degradation in vivo. Individual grains were no longer bonded to other grains and detached from the implant which had become rounded in shape. From in vitro mice experiments we found that PCP concentrations between 10−4 and 10−3 M resulted in45Ca-release from the bone HA. Our calculations showed, however, that only a total concentration of 1.4 × 10−4 M PCP was gradually released over the whole observation period. In another experiment, it appeared that a PCP concentration in solution &lt;10−3 M did not reduce ALP activity. It is concluded that release of PCP by the PCP–ALP-complexed implants is maintained at levels in the range to impair osteoclast bone resorption but not high enough to block osteoblast activity. The amount of ALP released can lead to induction of bone formation onto implant surfaces. pH-induced alterations in the microstructure and chemistry of the HA surface allow for controlled degradation of the HA implants in vitro. A PCP–ALP-complexed HA implant acting as temporary scaffolding for alveolar bone growth enhancement, mineralization, and maintenance seems to be a reasonable concept for preservation of the edentulous alveolus.
Secretory Products of Breast Cancer Cells Specifically Affect Human Osteoblastic Cells: Partial Characterization of Active Factors
Authors: Siwek Brigitte , Lacroix Marc , De Pollak Cindy , Marie Pierre , Body Jean-Jacques 
Published: April 2006

Abstract
The pathogenesis of tumor-induced osteolysis (TIO) following breast cancer metastases in bone remains unclear. We postulated that osteoblasts could be target cells for the secretory products of breast cancer cells. We previously showed that serum-free conditioned medium (CM) of the breast cancer cell line MCF-7 inhibits DNA synthesis by 75% of control values in osteoblast-like cells SaOS-2 and that this effect is only in a minor part due to transforming growth factor β secretion. To establish the specificity of our observations and to look for other biologically active factors, we have tested the effects of medium conditioned by several cancer and noncancer cell lines (breast, colon, placenta, or fibrosarcoma) on the proliferation of osteoblast-like cells (SaOS-2, MG-63), normal human osteoblasts, human fibrosarcoma cells, and normal human fibroblasts. Culture medium (1:2) of the breast cancer cell lines MCF-7, T-47D, MDA-MB-231, and SK-BR-3 inhibited by 25–50% the proliferation of osteoblast-like cells SaOS-2, MG-63, and normal osteoblasts as evaluated by the MTT survival test or [3H]thymidine incorporation. MCF-7 cells completely inhibited the proliferation of normal human osteoblasts in coculture. This inhibitory effect was reversible and not due to cytotoxicity. Moreover, the cyclic adenosine monophosphate (cAMP) response to parathyroid hormone (PTH) of osteoblast-like cells SaOS-2 was also increased by 100–240% by the same CM. Such activities were, however, not detected in medium from the breast noncancer cell line HBL-100 or in the medium conditioned by non–breast cancer cell lines (COLO 320DM, HT-29, JAR, or HT-1080). Medium from the breast cancer cells had no effect on normal human fibroblasts or fibrosarcoma cells (HT-1080), suggesting the specificity of their action on human osteoblasts. After partial purification by ultrafiltration and size-exclusion chromatography, we found that medium of T-47D cells contained at least three nonprostanoid factors of low molecular weights (apparent MW of 700, 1500, and 4000 D) which affected human osteoblast-like cells. These factors were heat stable and could be peptides without disulfide bonds. In summary, our data show that human breast cancer cells release soluble factors that inhibit osteoblast proliferation and increase their cAMP response to PTH, indicating that osteoblasts could be important target cells for breast cancer cells and could be involved in the process of TIO.
Role of Protein Kinase A in Collagenase-1 Gene Regulation by Prostaglandin E1: Studies in a Rabbit Synoviocyte Cell Line, HIG-82
Authors: Suzuki Koji , Rapuano Bruce E. , Bockman Richard S. 
Published: April 2006

Abstract
Gene expression of the matrix-degrading enzyme collagenase-1 in rabbit synoviocytes and human fibroblasts is down-regulated by prostaglandin E1 (PGE1) through a cyclic adenosine monophosphate (cAMP)–dependent pathway. In the current study, we examined the role of protein kinase A (PKA) in the PGE1-mediated effect on collagenase-1 gene expression. Collagenase-1 gene expression was rapidly induced several-fold above control both by a phorbol ester, 12-o-tetradecanoyl phorbol 13 acetate, and interleukin-1β (IL-1β) in HIG-82 synoviocytes. Treatment with PGE1 and forskolin increased PKA activity in the HIG-82 cells within 15 minutes of adding the stimulating agents. Two inhibitors of PKA, the isoquinoline-sulfonamide derivative, H-89 and a cAMP analog, RpcAMP, blocked the ability of PGE1 to down-regulate collagenase-1 gene expression. However, if PGE1 was added from 6 h to 30 minutes before the PKA inhibitor H-89, collagenase-1 gene expression was inhibited. Constitutive PKA activity was increased in HIG-82 synoviocytes stably transfected with an expression vector pCMV.Cα that caused the HIG-82 cells to overexpress an active catalytic subunit of PKA. Cells stably transfected with an inactive, mutated C-α-variant showed no change in PKA activity. Collagenase-1 mRNA levels in TPA-stimulated cells were reduced to baseline levels in the pCMV.Cα but not in the mutated C-α–transfected cells. These data show the importance of PKA in regulating collagenase-1 gene expression in a synoviocyte cell line.