bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal calcitonin suppresses increased bone resorption during short-term immobilization: A double-blind study of the effects of intranasal calcitonin on biochemical parameters of bone turnover
Authors: van der Wiel H.E. , Lips P. , Nauta J. , Kwakkel G. , Hazenberg G. , Netelenbos J.C. , van der Vijgh W.J.F. 
Published: February 2010

Abstract
Immobilization is associated with increased bone resorption and decreased bone formation. We evaluated in a double-blind trial the effect of intranasal administration of salmon calcitonin on biochemical parameters of bone turnover in 32 patients immobilized for a prolapsed intervertebral disk. Calcitonin in a dose of two times 200 IU/day partially inhibited the increase in the fasting 2 h urinary hydroxyproline/creatinine ratio (OHPr/Cr) and calcium/creatinine ratio (Ca/Cr). The increase in OHPr/Cr was 40% less in the calcitonin group compared to the placebo group (P = 0.01), and the increase in Ca/Cr was 80% less in the calcitonin group (P = 0.04). Calcitonin also partially inhibited the increase in serum cross-linked carboxyl-terminal telopeptide of collagen type I (P &lt; 0.05). The decrease in serum 1,25-dihydroxyvitamin D after 10 days of immobilization was significantly less in the calcitonin-treated group than in the placebo group (14 versus 29%, respectively; P &lt; 0.05). Intranasal calcitonin did not influence the pain scores as measured with a visual analog scale (VAS). The tolerability of the nasal calcitonin preparation was excellent. We conclude that nasal salmon calcitonin counteracts the early increase in bone resorption induced by immobilization.
Determinants of remission of paget's disease of bone
Authors: Patel S. , Stone M.D. , Coupland C. , Dr. Hosking D.J. 
Published: February 2010

Abstract
Bisphosphonates are a safe and effective treatment for Paget's disease of bone, but little information is available about the factors influencing the duration of remission so obtained. We assessed 60 patients with Paget's disease treated with disodium pamidronate (APD). The mean duration of remission was 9.5 months (range 3–25). The major influences were the initial pretreatment alkaline phosphatase (ALP; r = −4.6, p &lt; 0.0001), minimum posttreatment ALP (r = −0.51, p &lt; 0.0001), and the rate of response of bone turnover to the first dose of APD (r = 0.61, p &lt; 0.0001). Multiple linear regression showed that the initial response to treatment was the most significant influence. Also, despite a minimum ALP within the normal range, the duration of remission varied considerably (4–25 months). This may be due to the difficulties in applying a population-based normal range to individuals.
Macrophage colony-stimulating factor release and receptor expression in bone cells
Authors: Dr. Weir Eleanor C. , Horowitz Mark C. , Baron Roland , Centrella Michael , Kacinski Barry M. , Insogna Karl L. 
Published: February 2010

Abstract
Colony-stimulating factors (CSF) may play a role in bone resorption. To examine whether osteoblasts secrete colony-stimulating activity (CSA) in response to parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP), conditioned medium (CM) from ROS 17/2.8 cells and primary rat osteoblasts were examined for induction of clonal growth of cultured rat bone marrow cells. Untreated cells constitutively secreted CSA, which increased with PTH and PTHrP treatment. The colonies formed were principally comprised of macrophages, and preincubation of CM with antiserum to murine macrophage colony-stimulating factor (M-CSF) neutralized most of the CSA, suggesting that the osteoblast-derived CSA was predominantly due to M-CSF. PTHrP treatment upregulated steady-state M-CSF mRNA levels. To investigate a paracrine role for M-CSF in bone we examined bone tissue and cells for the M-CSF receptor c-fms using immunohistochemical techniques and demonstrated staining of mature osteoclasts both in situ and after isolation. We conclude that M-CSF is responsible for the majority of the CSA released by PTH- and PTHrP-treated rat osteoblasts. In addition we identified CSF-1 receptor expression in mature osteoclasts. These data suggest that M-CSF is a mediator of osteoblast-osteoclast interaction in PTH- and PTHrP-induced bone resorption.
Journal of Bone and Mineral Research
Authors: Veis Arthur 
Published: February 2010

Abstract
The bone, dentin, and cementum of the mature individual are comprised from a dense collagenous fiber network into which the carbonate-apatite mineral phase is deposited. It is hypothesized that a set of collagen-interactive acidic phosphoproteins are secreted by the osteoblasts, odontoblasts, and cementoblasts into the preformed collagenous matrix. These proteins then interact specifically with the collagen and nucleate apatite formation on and within the fibrils. These phosphoproteins may also regulate the morphology, rate of growth, and stability of the mineral phase crystals. The acidic matrix phosphoproteins may thus be considered as the crucial regulators of mineralization and tissue stability. In the dentin system, these regulatory proteins are synthesized, posttranslationally modified, and secreted in vesicles different from the collagen secretory vesicles. Mineralization occurs as the regulatory proteins are deposited on the preformed fibrils. This model requires testing in the bone system. In dentin, in the absence of tissue turnover, the resident phosphoproteins are degraded in situ over time, perhaps changing the properties of the tissue. Regulation of synthesis, secretory pathways and retention of integrity within the matrix are thus important areas for further investigation.
Journal of Bone and Mineral Research
Authors: Cann Christopher E. 
Published: February 2010

Abstract
The primary role of radiographic imaging in dental health has been the detection and localization of disease as a guide for surgical intervention. In this role, it appears to differ from the primary role of postcranial skeletal radiography, evaluation of the structural integrity of the bone. However, in both cases, the radiographic information ultimately is used in an attempt to restore or maintain function in the affected osseous structure. This structure-function relationship can be used as a framework within which the potential of new technologies developed for evaluation of the postcranial skeleton can be assessed relative to craniofacial imaging. Within this context, I treat first the use of newer imaging modalities, followed by methods to assess bone properties, and finally the coupling of these technologies with other analytic tools to obtain direct information about the structure-function relationship in the cranioskeleton.
CD44 expression in human bone: A novel marker of osteocytic differentiation
Authors: Hughes D.E. , Salter D.M. , Simpson R. 
Published: February 2010

Abstract
CD44 is a transmembrane glycoprotein with cell-cell and cell-matrix adhesion functions that is expressed by a wide variety of cell types and has a number of known biologic functions. Because of its ability to bind matrix macromolecules, such as fibronectin, collagen, and hyaluronate, we investigated the possibility that it is expressed by the cells of bone, the matrix receptors of which are largely unknown. Immunohistochemical study of a variety of sources of human bone was carried out using a panel of six well-characterized anti-CD44 monoclonal antibodies. Osteocytes strongly expressed CD44, whereas osteoblasts and lining cells were negative. Osteoclasts and periosteal cells also expressed CD44, although not as strongly as osteocytes. These patterns of staining were observed with all six antibodies. These results demonstrate that acquisition of CD44 immunoreactivity is a sensitive marker of osteocytic differentiation and raise the possibility that CD44 acts as a cell matrix receptor in bone.
Transcriptional activation of the human osteocalcin gene by basic fibroblast growth factor
Authors: Schedlich Lynette J. , Flanagan Judith L. , Crofts Linda A. , Gillies Susan A. , Goldberg Daniella , Morrison Nigel A. , Eisman John A. 
Published: February 2010

Abstract
Basic fibroblast growth factor (bFGF) has been detected in bone cells and stimulates osteoblast proliferation; however, its role in the regulation of bone metabolism remains speculative. We demonstrated that the human osteocalcin promoter is activated by bFGF when transfected into rat osteoblastic (ROS 17/2.8) cells. This effect is concentration dependent, with a twofold induction at 10 ng/ml detected after 20 h. The bFGF response is independent of both the 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and retinoic acid activation of the osteocalcin promoter. To identify the promoter sequences through which bFGF exerts its effect, we tested a series of promoter deletion constructs for their response to bFGF. Deletion of the upstream region between −673 and −588 bp results in a significant loss of induction. Gel-shift analysis demonstrates that proteins present in ROS 17/2.8 nuclear extracts bind specifically to these sequences. This region alone was unable to confer the bFGF response on a minimal osteocalcin or an heterologous promoter. However, sequences between −678 and −476 bp, which also includes the vitamin D response element (VDRE), were able to confer bFGF inducibility on both a minimal osteocalcin and a heterologous promoter. These data suggest that induction of the human osteocalcin promoter by bFGF requires the interaction of more than one sequence element.
Role of chondroitin sulfate glycosaminoglycans in mineralizing osteoblast-like cells: Effects of hormonal manipulation
Authors: Slater M. , Patava J. , Mason R.S. 
Published: February 2010

Abstract
A monoclonal anti-chondroitin sulfate antibody (CS-56) that recognizes native chondroitin sulfate glycosaminoglycans (CSGAG) was used to quantify changes in CSGAG labeling levels in mineralizing human fetal osteoblast-like cell multilayers up to 40 days postconfluence. In control cultures, mean labeling of CSGAG increased in nonmineralized areas from around eight gold probes per μm2 (gpm) at 20 days to 26 gpm at 40 days. Labeling was markedly increased in the mineralized tissue, to 560 gpm at 30 days and 580 gpm at 40 days. In β-glycerophosphate-treated cultures, the mineralized areas were increased and appeared earlier (20 days) than in the control cultures. In these cultures, mean CSGASG labeling increased in nonmineralized areas from around 5 gpm at 20 days to 26 gpm at 30 days and was further increased in mineralized areas to 270 gpm at 20 days and 298 gpm at 30 days. Mineralization was not noted in cultures treated with 10−8 M 1,25-dihydroxyvitamin D, and CSGAG labeling remained low (&lt;5 gpm) during the study period. These results indicate that an increase in immunoreactive CSGAG is associated with mineralization in this culture system. One possible interpretation of these findings is that proteoglycan molecules or at least their CSGAG side chains may be involved in the mineralization process.
Characterization of the stromal osteogenic cell line MN7: mRNA steady-state level of selected osteogenic markers depends on cell density and is influenced by 17β-estradiol
Authors: Mathieu E. , Dr. Merregaert J. 
Published: February 2010

Abstract
The steady-state mRNA levels of different osteogenic markers and their modulation by 17β-estradiol in the murine osteogenic cell line MN7 during proliferation and differentiation in vitro were examined. mRNA of collagen type I, osteopontin, bone morphogenetic protein 2, plasminogen activator inhibitor 1, alkaline phosphatase, and osteocalcin were isolated from MN7 cultures grown for 7, 11, 14, and 17 days. Northern blot analysis revealed steady-state transcript levels depending on MN7 cell density. The order of appearance of Col I, OP, ALP, and OC resembled the pattern of gene expression observed during osteoblast maturation in vitro. Furthermore, PAI-1 steady-state transcript levels peaked during subconfluence (day 11) but BMP-2 RNA levels reached their maximum after the culture had become confluent. 17β-Estradiol showed a dose-dependent stimulation of the different osteoblast-related transcripts present in a subconfluent MN7 culture at the time of analysis. Furthermore, the effects of 17β-estradiol (17βE2) at different time points of MN7 growth varied according to cell density. 17βE2 added to subconfluent MN7 cultures modulated the transcript level in a negative way, but RNA levels of the investigated osteogenic markers in confluent cultures were stimulated with 100 nM 17β-estradiol. No effect of 17β-estradiol on proliferation was detected. The present studies have revealed differential osteoblast gene expression related to MN7 cell proliferation and differentiation in vitro and emphasize the importance of 17βE2 in the regulation of growth of this preosteoblastic cell line in vitro.
Temporal changes in matrix protein synthesis and mRNA expression during mineralized tissue formation by adult rat bone marrow cells in culture
Authors: Yao Kam-Ling , Todescan Reynaldo , Dr. Sodek Jaro 
Published: February 2010

Abstract
To characterize the bone-like tissue produced by rat bone marrow cells (RBMC) from young adult femurs, the synthesis of bone proteins and the expression of their mRNA were studied in vitro. RBMC plated at a density of 5 × 103 cells/cm2 and grown in the presence of 10−8 M dexamethasone (Dex) and 10 mM β-glycerophosphate (β-GP) produced mineralized bone nodules, which were first evident at day 3 and increased markedly to day 13. However, in the absence of dexamethasone, few mineralized nodules were observed. The formation of mineralized nodules was reflected by the uptake of 45Ca, which also increased markedly to day 13. Analysis of bone protein expression by Northern and slot-blot hybridizations revealed an increase in mRNA levels of collagen type I (Col I), osteonectin/SPARC (ON), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and osteocalcin (OC) during the formation of mineralized nodules. Whereas the Col I, ON, ALP, and OPN mRNAs were expressed before the formation of mineralized nodules was evident and were also expressed at various levels in the absence of Dex, the expression of BSP and OC mRNA was induced in the bone-forming cultures. The expression of BSP mRNA was correlated temporally with bone tissue formation, reaching maximal levels on day 16. In contrast, OC mRNA was expressed later and, following induction, increased over the 28 day culture period. Production of matrix proteins during the rapid formation of the bone tissue appeared to reflect the levels of the respective mRNAs. However, whereas some of the collagen and almost all of the SPARC were secreted into the culture medium, virtually all of the OPN and most of the BSP were extracted from the mineralized tissue matrix with EDTA. Some OPN and BSP were present in the medium, especially early in the culture, and a significant amount of BSP was also found associated with the collagenous tissue matrix. These studies point to the importance of Col I, ALP, OPN, and BSP, but not ON or OC, in the initial formation of bone tissue.
Upstream regulatory elements necessary for expression of the rat COL1A1 promoter in transgenic mice
Authors: Bogdanovic Zoran , Bedalov Antonio , Krebsbach Paul H. , Pavlin Dubravko , Woody Charles O. , Clark Stephen H. , Thomas Huw F. , Rowe David W. , Kream Barbara E. , Lichtler Alexander C. 
Published: February 2010

Abstract
The activity of fusion genes containing fragments of the COL1A1 promoter was measured in tissues from 6- to 8-day-old transgenic mice. ColCAT3.6 contains approximately 3.6 kb (-3521 to 115 bp) of the rat COL1A1 gene, the chloramphenicol acetyltransferase (CAT) reporter gene, and the SV40 splice and polyadenylation sequences. ColCAT2.3 and ColCAT1.7 are deletion constructs that contain 2296 and 1667 bp of COL1A1 upstream from the RNA start site, respectively. For each transgene, up to six lines of mice were characterized. Both ColCAT3.6 and ColCAT2.3 had similar activity in bone and tooth; ColCAT1.7 was inactive. In transgenic calvariae, levels of transgene mRNA paralleled levels of CAT activity. In tendon, the activity of ColCAT2.3 was 3- to 4-fold lower than that of ColCAT3.6, and the activity ColCAT1.7 was 16-fold lower than that of ColCAT2.3. There was little activity of the ColCAT constructs in liver and brain. These data show that DNA sequnces between −2.3 and −1.7 kb are required for COL1A1 promoter expression in bone and tooth; sequences that control expression in tendon are distributed between −3.5 and −1.7 kb of the promoter, with sequences downstream of −1.7 kb still capable of directing expression to this tissue. The cis elements that govern basal expression of COL1A1 in transgenic calvariae appear to be different from those required for optimal expression of the COL1A1 promoter in stably transfected osteoblastic cells.
Influence of early age at menopause on vertebral bone mass
Authors: Pouillès J.M. , Trémollières F. , Bonneu M. , Dr. Ribot C. 
Published: February 2010

Abstract
Menopause leads to rapid bone loss, mainly as a result of estrogen deficiency superimposed on the age-related linear bone loss. The influence of age at menopause on bone loss is unclear, although early menopause is widely considered a risk factor for osteoporosis. Vertebral bone mineral density (BMD) was measured in 1667 women divided into five groups according to hormonal status and age at menopause. Menopausal status was an independent predictor of BMD in a multiregression analysis, along with current age, years since menopause (YSM), weight, and height. For the same chronologic age (55 years), women with early menopause had a 15% lower BMD and a higher YSM than women whose menopause occurred later (“normal” menopause). After adjusting for the interval since menopause, postmenopausal women with early menopause were found to have lower vertebral BMD than postmenopausal women with normal menopause. Finally, after the age of 60,66% of the women with early menopause had a BMD that was below the fracture threshold compared to 18% of the women with normal menopause. The results of this cross-sectional study suggest that early menopause is associated with a quantitatively higher bone loss than in women with menopause of later onset and thus constitutes a risk factor for osteoporosis.
Characterization, regulation, and function of specific cell membrane receptors for insulin-like growth factor I on bone endothelial cells
Authors: Fiorelli Gianna , Orlando Claudio , Benvenuti Susanna , Franceschelli Francesco , Bianchi Sandro , Pioli Piero , Tanini Annalisa , Serio Mario , Bartucci Francesco , Dr. Brandi Maria Luisa 
Published: February 2010

Abstract
It is now widely accepted that insulin-like growth factor-I (IGF-I) has a local regulatory role in bone remodeling. IGF-I has also been demonstrated to regulate proliferation of bone-derived endothelial cells. Such studies suggest a role of IGF-I in skeletal angiogenesis. Using BBE cells, a bovine bone endothelial cell line, we characterized the kinetics and chemical properties of IGF-I receptors and examined the effect of IGF-I on bone endothelium migration. Two classes of binding sites with high affinity for IGF-I were detected by binding experiments on bone endothelial cells. Both competition analyses and cross-linking studies revealed the presence of type I IGF receptor in bone endothelial cells. Moreover, these cells produced and released authentic IGF-I into the medium, as evidenced by radioimmunoassay analyses of gel-filtered conditioned media. Both IGF-I binding capacity and release decreased either with increases in cell number or after treatment with 17β-estradiol (17βE2) and parathyroid hormone (PTH). Both hormones also inhibited chemotactic responses of bone endothelial cells to IGF-I. Taken together, these results strongly suggest that IGF-I, a growth factor that promotes the proliferation of various bone cell types, also induces growth and chemotactic responses in bone endothelium acting through the type I IGF receptor. This may be part of a generalized response of bone cells to IGF-I that facilitates cell migration.
Cloning and sequence analysis of bovine bone sialoprotein cDNA: Conservation of acidic domains, tyrosine sulfation consensus repeats, and RGD cell attachment domain
Authors: Chenu C. , Ibaraki K. , Robey P. Gehron , Delmas P.D. , Young M.F. 
Published: February 2010

Abstract
We isolated and sequenced a cDNA encoding bovine bone sialoprotein (BSP) using a bovine cDNA library made from mRNA isolated from bone-derived cell cultures and ligated to a phage λgt11. One of the cDNA clones isolated from this library had a 1800 base pair long insert and was found to contain the entire protein-encoding region. The deduced protein sequence revealed a 310 amino acid protein containing a signal peptide sequence of 16 hydrophobic amino acids. The protein sequence shows remarkable conservation with previously published human and rat sequences (more than 80% similarity for both species). The potential functional domains of BSP, including three acid amino acid-rich sequences, tyrosine sulfation consensus repeats, and the RGD cell binding sequence, are all present in the bovine sequence. Northern analysis of RNA from different bovine tissues indicated the presence of BSP message in bone but not in other nonmineralized tissues, confirming that bone is the major site of BSP message production.
Osteoclast synthesis and secretion and activation of latent transforming growth factor β
Authors: Oursler Merry Jo 
Published: February 2010

Abstract
The coupling of bone resorption and formation suggests that autocrine and paracrine factors are produced and released within the local bone environment. Since osteoblasts secrete latent transforming growth factor β (TGF-β), and osteoclasts can activate this latent complex, one candidate paracrine coupling factor is TGF-β. To examine whether TGF-β is also a potential osteoclast-derived autocrine and paracrine factor, highly purified avian osteoclasts were examined for synthesis of TGF-β and the mechanism by which osteoclasts activate the latent TGF-β complex was investigated. TGF-β protein production was measured within 4 h of culture in osteoclast-conditioned media using growth factor inhibition of CCL-64 cells and verified by blocking effects with anti-TGF-β antibodies. Synthesis of TGF-β was confirmed by northern blotting and metabolic labeling. Northern blots of total RNA revealed that osteoclasts expressed the mRNA for TGF-β2, β3, and β4. Biosynthetic studies suggest that TGF-β2 was the principle form secreted in culture. Nearly all the TGF-β that was secreted had been activated by the osteoclasts. When presented with exogenous latent TGF-β, osteoclasts activated latent TGF-β from a variety of sources. Furthermore, osteoclast-conditioned media retained the ability to activate latent TGF-β during cell-free incubations at 37°C. Osteoclast-mediated activation was inhibited by proteinase inhibitors, weak base treatment of the cells, or disruption of the cytoskeletal network. These data suggest that osteoclasts may secrete proteinases into the extracellular milieu to activate latent TGF-β and that TGF-β may be an autocrine factor involved in regulating osteoclast activity.