bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of an Avian Bone Sialoprotein (BSP) cDNA: Comparisons to Mammalian BSP and Identification of Conserved Structural Domains
Authors: Yang Renji , Gotoh Yozo , Moore Mark A. , Rafidi Krishna , Gerstenfeld Louis C. 
Published: February 2010

Abstract
Bone sialoprotein (BSP) is one of the major noncollagenous proteins found in mineralized vertebrate tissue. It is an acidic glycoprotein containing a high sialic acid content and is phosphorylated on several of its Ser and Thr residues. While it has been extensively characterized from various mammalian species, little is known about its sequence or expression in lower vertebrates. The cloning and characterization of several cDNAs encoding the chicken bone sialoprotein are reported here. A partial cDNA clone encoding the carboxyl terminus of the protein was initially isolated from a λGT11 expression library using a polyclonal antibody against BSP purified from chicken bone matrix. Subsequently, several additional clones were obtained by further screening and by reverse transcription polymerase chain reaction (RT-PCR). Three overlapping clones encompassing about 1 kb, which included the complete coding sequence for BSP, were analyzed. The deduced amino acid sequence revealed that chicken BSP contains 276 amino acid residues. Although the overall identity between chicken and mammalian BSP is only ∼39%, the diversity in amino acid sequence occurs mostly between the major functional domains of this molecule. These domains include: (1) three acidic poly-Glu regions; (2) two tyrosine-rich domains, which may be sites for protein sulfation; (3) several casein kinase II phosphorylation sites; (4) an Asn glycosylation site; and (5) an RGD cell-binding motif. Of interest in the chicken BSP is the identification of two additional RGD motifs within the avian sequence, unlike the mammalian forms of BSP which has only one. The existence of several consecutive gly-x-y triplets in the molecule suggest that it may bind to collagen, which is consistent with the fact that BSP protein is tightly associated with the matrix. Northern blot analysis demonstrated that chicken BSP was expressed specifically in bone tissue, and its expression was detected as early as Day 12 during chicken embryogenesis. BSP expression preceded osteopontin (OPN) expression, reaching maximal levels during embryogenesis in contrast to that of OPN, which only reaches its highest level of expression several weeks after hatching.
Low bioavailable testosterone levels predict future height loss in postmenopausal women
Authors: Jassal Simerjot K. , Barrett-Connor Elizabeth , Edelstein Sharon L. 
Published: February 2010

Abstract
The objective of this study was to examine the relation of endogenous sex hormones to subsequent height loss in postmenopausal women, in whom height loss is usually a surrogate for osteoporotic vertebral fractures. This was a prospective, community-based study. The site chosen was Rancho Bernardo, an upper middle class community in Southern California. A total of 170 postmenopausal women participated, aged 55–80 years. None of them were taking exogenous estrogen between 1972 and 1974. Plasma was obtained for sex hormone and sex hormone-binding globulin (SHBG) assays. Estradiol/SHBG and testosterone/SHBG ratios were used to estimate biologically available hormone levels; bioavailable (non-SHBG-bound) testosterone was measured directly in 60 women. Height loss was based on height measurements taken 16 years apart. Height loss was strongly correlated with age (p = 0.001). These women lost an average 0.22 cm/year in height. Neither estrone nor estradiol levels were significantly and independently related to height loss. Both estimated bioavailable testosterone (testosterone/SHBG ratio) and measured bioavailable testosterone levels predicted future height loss (p = 0.02 and 0.08, respectively) independent of age, obesity, cigarette smoking, alcohol intake, and use of thiazides and estrogen. We conclude that bioavailable testosterone is an independent predictor of height loss in elderly postmenopausal women. The reduced height loss is compatible with a direct effect of testosterone on bone mineral density or bone remodeling.
Prevention of hypercalciuria and stone-forming propensity during prolonged bedrest by alendronate
Authors: Ruml Lisa A. , Dubois Susan K. , Roberts Marsha L. , Pak Charles Y.C. 
Published: February 2010

AbstractThe bone loss and hypercalciuria induced by immobilization or the decreased gravitational forces of space are well described. Using a model of bedrest immobilization, the ability of a potent aminobisphosphonate, alendronate, to avert hypercalciuria and stone-forming propensity was tested. Sixteen male subjects participated in a randomized, placebo-controlled trial in which they received either 20 mg of alendronate or placebo 2 weeks prior to and during 3 weeks of strict bedrest. Parameters of bone and calcium metabolism and urinary crystallization of stone-forming salts were measured before and at the end of bedrest. In the placebo group, bedrest increased urinary calcium (209 ± 47 to 267 ± 60 mg/day, p &lt; 0.01) and the saturation of calcium phosphate. Before bedrest, the alendronate group had a significantly lower serum calcium (8.8 ± 0.4 vs. 9.6 ± 0.5 mg/dl, p ≥ 0.01) and higher serum PTH (62.4 ± 33.1 vs. 23.1 ± 7.5 pg/ml, p &gt; 0.01) compared with the placebo group. Moreover, the alendronate group had a lower urinary calcium (75 ± 41 mg/day) and saturation of calcium oxalate and calcium phosphate. These effects of alendronate were sustained during bedrest. Following bedrest in the alendronate group, urinary calcium rose to 121 ± 50 mg/day, a value less than that in the placebo group before or during bedrest. Similarly, urinary saturation of calcium oxalate and calcium phosphate rose with bedrest in the alendronate-treated patients but remained lower than values obtained in placebo-treated patients before or during bedrest. Alendronate inhibits bone mineral loss and averts the hypercalciuria and increased propensity for the crystallization of stone-forming calcium salts which occurs during 3 weeks of strict bedrest.
Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents
Authors: Ruiz J.C. , Mandel C. , Dr. Garabedian M. 
Published: February 2010

Abstract
Peak bone mass is determined mainly by genetic-ethnic factors, but environmental factors such as calcium intake and physical activity during childhood and adolescence could play a role. We have measured the bone mineral density (BMD) of 151 healthy children and adolescents, ages 7–153 years. Density was measured by dual X-ray absorptiometry (DXA) at two sites (lumbar verterbrae L1–L4 and the upper femur), and the data were analyzed in terms of the height, weight, sexual maturation, spontaneous calcium intake, and physical activity. Of the children, 57–71% had calcium intakes below 1000 mg/day. BMD increased with pubertal maturation from 0.68 ± 0.08 to 0.92 ± 0.09 g/cm2 (vertebral bone density, VBD) and from 0.87 ± 0.10 to 1.03 ± 0.09 g/cm2 (femoral bone density, FBD) between Tanner stage 1 and 5. Multiple regression analysis showed that body weight and Tanner stage were main determinants of bone density when expressed as g/cm2. The weekly duration of sports activity also influenced both the vertebral (p &lt; 0.001) and femoral (p = 0.01) sites, especially in girls and during puberty. Dietary calcium appeared to be another independent determinant of BMD, especially before puberty, at the vertebral (p = 0.02) site. Most important, dietary calcium was found to be the main determinant of vertebral mineral density, when expressed as z score, in both sexes. Moreover, 93% of the 28 children with low vertebral z score values (below –1) and 84% of the 31 children with low femoral z score values (below –1) had dietary calcium intakes below 1000 mg/day.
Inhibitors of ER Ca2+-ATPase activity deplete the ATP- and thrombin-sensitive Ca2+ pool in UMR 106–01 osteosarcoma cells
Authors: Meszaros Gary J. , Dr. Karin Norman J. 
Published: February 2010

Abstract
While calcium release from intracellular stores is a signaling mechanism used universally by cells responding to hormones and growth factors, the compartmentalization and regulated release of calcium is cell type-specific. We employed thapsigargin and 2,5,-di-(tert-butyl)-1,4-benzohydroquinone (tBuHQ), two inhibitors of endoplasmic reticulum (ER) Ca2+-ATPase activity which block the transport of Ca2+ into intracellular stores, to characterize free Ca2+ compartmentalization in UMR 106–01 osteoblastic osteosarcoma cells. Each drug elicited transient increases in cytosolic free Ca2+ ([Ca2+]i), followed by a stable plateau phase which was elevated above the control [Ca2+]i. The release of Ca2+ from intracellular stores was coupled to an increased plasma membrane Ca2+ permeability which was not due to L-type Ca2+ channels. Thapsigargin and tBuHQ emptied the intracellular calcium pool which was released in response to either ATP or thrombin, identifying it as the inositol 1,4,5-trisphosphate-sensitive calcium store. The results of sequential and simultaneous additions of thapsigargin and tBuHQ indicate that both drugs depleted the same Ca2+ store and inhibited the same Ca2+-ATPase activity.
Peak bone mass in young women
Authors: Teegarden Dorothy , Proulx William R. , Martin Berdine R. , Zhao Jian , Mccabe George P. , Lyle Roseann M. , Peacock Munro , Slemenda Charles , Johnston Conrad C. , Weaver Connie M. 
Published: February 2010

Abstract
Increasing peak bone mineral density (BMD) or content (BMC) in young women may help to reduce the incidence of osteoporosis. Identifying the age when peak bone content or density is attained is essential to develop strategies aimed at optimizing peak BMD and BMC. Total body bone mineral density (TBBMD) and content (TBBMC) were measured by a dual X-ray absorptiometer in healthy females (n = 247, aged 11–32 years). TBBMD and TBBMC were modeled separately as a nonlinear function of age. By age 22.1 ± 2.5 years, 99% of peak BMD is attained, and by age 26.2 ± 3.7 years, 99% of peak BMC is attained. Nonlinear relationships between weight and TBBMD or TBBMC were also modeled. In this model, the influence of several parameters, including age, weight, and height, on BMC and BMD were simultaneously assessed. A model with age and weight described the best fit for TBBMD, whereas age, weight, and height described the best fit for total body TBBMC.
Thapsigargin stimulates intracellular calcium mobilization and inhibits parathyroid hormone release
Authors: Dr. Shoback Dolores , Chen Tsui-Hua , Pratt Stacy , Lattyak Bruce 
Published: February 2010

Abstract
Ca2+ and other divalent cations like Sr2+, Ba2+, and Mg2+ stimulate rapid and sustained increases in intracellular Ca2+ ([Ca2+]i) and 1,4,5-inositol trisphosphate (1,4,5-InsP3) presumably by interacting with recently identified parathyroid cell membrane Ca2+ receptors. We used thapsigargin (THAPS), an inhibitor of the microsomal Ca2+-ATPase, to deplete InsP3-sensitive intracellular Ca2+ stores to determine whether sustained increases in [Ca2+]i due to divalent cations require intact cytosolic Ca2+ pools. In Fura 2-loaded parathyroid cells, THAPS produced a gradual increase in [Ca2+]i which reached a steady-state level by 2–3 minutes. The effect of THAPS (3 × 10−6 M) was substantial with [Ca2+]i, rising from 281 ± 27 nM at 0.5 mM Ca2+ to a peak value of 684 ± 30 nM (p &lt; 0.0001). The addition of Sr2+ to cells at 0.5 mM extracellular Ca2+ induced an immediate 2-to 3-fold increase in [Ca2+]i which stabilized at a [Ca2+]i above baseline for ≥10 minutes. THAPS (3 × 10−6 M) pretreatment for ≥5 minutes blocked this sustained-phase increment in [Ca2+]i due to Sr2+. In the absence of extracellular Ca2+, there was a slight but nonsignificant effect of THAPS on [Ca2+]i. Incubation of cells with THAPS did not change the levels of 3H-inositol phosphates (InsP3, InsP2, and InsP1) or alter Sr2+-induced accumulation of InsP3, InsP2, and InsP1. THAPS substantially reduced parathyroid hormone secretion at 1.0 mM Ca2+ by 20 ± 16, 57 ± 8, 75 ± 10, and 83 ± 9% at 10−7, 3 × 10−7, 10−6, and 3 × 10−6 M THAPS, respectively. We conclude that depletion of intracellular Ca2+ stores by THAPS stimulates Ca2+ mobilization, presumably from extracellular sources, and that this agent and divalent cations such as Sr2+ activate the same pathway for sustained Ca2+ mobilization. The inhibition of secretion by THAPS supports the idea that increases in [Ca2+]i play a suppressive role in the control of hormone release in the parathyroid.
Generation and characterization of a human osteosarcoma cell line stably transfected with the human estrogen receptor gene
Authors: Huo Bin , Dossing Debra A. , Dimuzio Michael T. 
Published: February 2010

Abstract
Although 17β-estradiol (E2) replacement therapy has been shown to be effective in treating postmenopausal osteoporosis, the underlying mechanism remains unclear. The presence of low levels of functional endogenous estrogen receptor (ER) in some osteoblastic cells has been demonstrated, and the suggestion that the abundance of ER may be rate-limiting in the action of E2 on these cells has been made. To study the mechanism of ER in regard to E2-mediated effects, we stably transfected a human osteosarcoma cell line, SaOS-2, with an expression vector, pMV-7-ER, containing the human ER gene. We characterized six of the stably transfected clones. One of the stable clones, SaOS-2-ER, expressed extra copies of ER genes integrated into the genome as detected by Southern blot analysis, showed a significantly increased level of ER mRNA by RT-PCR, and contained an increased level of ER cytosolic protein as detected by an ER-specific EIA. The overexpressed ER was functional and sensitive to E2 in a dose-dependent fashion after transient transfection with a vector containing an estrogen response element (ERE) linked to a chloramphenicol acetyltransferase (CAT) reporter gene. Scatchard analysis revealed a single high-affinity binding site with a Kd similar to values obtained for the ER in MCF-7 breast cancer cells. These SaOS-2-ER cells had altered osteoblast phenotypic features including growth inhibition, decreased basal alkaline phosphatase activity, and decreased IL-6 expression and secretion. In response to E2, a greater than 2-fold increase in TGF-β1 mRNA was quantitatively measured in these ER-overexpressing osteoblasts. These cells may provide a sensitive and unique model for understanding the mechanism of E2 and ER in overall bone metabolism.
Physical exercise during remobilization restores a normal bone trabecular network after tail suspension-induced osteopenia in young rats
Authors: Dr. Bourrin Sandrine , Palle Sabine , Genty Christian , Alexandre Christian 
Published: February 2010

Abstract
To determine how bone recovers from immobilization-induced bone loss and to specify whether its recovering capacity is improved by physical exercise, 5-week-old male Wistar rats (287.07 g ± 10.65 SD) were tail suspended for 14 days, then returned to either normal weight-bearing (R) or controlled physical exercise for 28 days (R + E). Bone mineral density (BMD) was measured in three parts of the femur. Using histomorphometric analysis, bone mass and architecture were estimated in the primary (1°sp) and secondary spongiosa (2°sp) of the proximal tibial metaphysis. Bone cellular parameters were measured in the 2°sp of the tibia. Tail suspension induced a significant decrease in BMD, 2°sp bone mass, mineral apposition rate, and bone formation rate and marked alterations of the trabecular network. In R rats, BMD was still significantly decreased, except in the distal part of the femur. Long-bone lengthening was significantly altered. The 2°sp bone mass returned to the age-matched control values; however, the trabeculae were still significantly thinner and bone resorption was significantly higher. R + E rats had a normal long bone lengthening and a significant increase in 2°sp bone mass and trabecular thickness when compared with R rats. Bone resorption was significantly depressed, and osteoid surfaces and thickness were significantly increased. Thus, although bone mass returns to normal values in the R group, trabecular alterations persist. Physical exercise during recovery helps restore a normal trabecular network, and the depressed bone resorption associated with an increased bone formation leads to an increased bone volume.
The skeletal effects of spaceflight in growing rats: Tissue-specific alterations in mrna levels for TGF-β
Authors: Dr. Westerlind Kim C. , Turner Russell T. 
Published: February 2010

Abstract
Dynamic weight bearing is important for normal growth and maintenance of the skeleton in humans and laboratory animals. Transforming growth factor-beta (TGF-β) has been implicated as having autocrine and paracrine actions in bone. The purpose of this study was to examine mRNA levels of TGF-β in skeletal tissues of growing male rats following skeletal unweighting during an 11-day spaceflight. Animals were sacrificed 5–8 h after the skeleton was reloaded. Spaceflight resulted in decreases in cortical bone area and periosteal bone formation, but no change in medullary area and endocortical bone formation. In addition, spaceflight had no effect on longitudinal bone growth. TGF-β was reduced relative to the ground controls in the hindlimb periosteum, but was not significantly altered in the growth zone of the tibial metaphysis. Similarly, mRNA levels for type I collagen were reduced in the periosteum, but not in the metaphysis of flight animals. The results suggest a potential role of TGF-β as an intermediate in the signal transduction pathway for mechanical loading. Further, they indicate skeletal tissue compartment-dependent changes in mRNA levels for TGF-β following weightlessness.
Comparison of methods for defining prevalent vertebral deformities: The study of osteoporotic fractures
Authors: Black Dennis M. , Palermo Lisa , Nevitt Michael C. , Genant Harry K. , Epstein Robert , Valentin Ria San , Cummings Steven R. 
Published: February 2010

Abstract
Women with vertebral deformities caused by osteoporosis have more back pain and disability and are at higher risk for subsequent vertebral deformities than women without deformities. Despite the importance of vertebral deformities, there has been a great deal of controversy about how to identify or define them. In order to compare methods for defining vertebral deformities, we studied spinal radiographs from women in the Study of Osteoporotic Fractures (SOF), a cohort study of 9704 non-black women over age 65 recruited from population-based listings in four clinical centers. Using radiographs obtained at the baseline exam, we compared five methods for defining vertebral deformities: one based on a semiquantitative reading by a radiologist and four using vertebral morphometry. The semiquantitative method was compared with the other methods in a random sample of 503 films, while the morphometric methods were compared with each other in a larger sample of 9575 films. We tested a system of “triage” in which only those films with evidence of deformity were assessed by morphometry. We compared the relationship between deformity, defined by each method, and a variety of clinical criteria including bone mineral density at the lumbar spine, height loss since age 25, back pain, and incidence of subsequent deformity. Semiquantitative reading and three of the four morphometry-based methods provided similar relationships to clinical criteria. The fourth morphometry method (based on ratios of each vertebral height to the corresponding height at T4) produced significantly weaker relationships for several of the clinical validation criteria. Triage of radiographs rarely resulted in missed deformities and did not reduce the performance of any of the methods. We conclude that use of any of the similar methods, with or without triage, provides a valid approach to defining vertebral deformities.
Childhood growth, physical activity, and peak bone mass in women
Authors: Dr. Cooper Cyrus , Cawley Michael , Bhalla Ashok , Egger Peter , Ring Francis , Morton Linda , Barker David 
Published: February 2010

Abstract
Peak bone mass is an important determinant of the risk of osteoporotic fracture, and preventive strategies against osteoporosis require a clear understanding of the factors influencing bone gain in early life. We report a longitudinal study aiming to identify the relationships between childhood growth, lifestyle, and peak bone mass in women. One hundred and fifty-three women born in a British city during 1968–1969 were traced and studied in 1990. Data on their growth in childhood was obtained from linked birth and school health records; current bone mineral measurements were made by dual X-ray absorptiometry. There were statistically significant associations between weight at 1 year and BMC (but not BMD) at the lumbar spine (r = 0.32, p &lt; 0.01) and femoral neck (r = 0.26, p &lt; 0.01). These remained significant after adjusting for current weight. There were also strong relationships between childhood height measurements and adult BMC at the two skeletal sites. Physical activity was the major lifestyle determinant of BMD after allowing for body build. We conclude that infant growth and physical activity in childhood are important determinants of peak bone mass in women. Growth primarily determines the size of the skeletal envelope, and its trajectory is established by age 1 year. Activity, in contrast, modulates the mineral density within the skeletal envelope and may contribute to the consolidation of bone following the end of linear growth.