bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal Smoking During Pregnancy, Growth, and Bone Mass in Prepubertal Children
Authors: Jones Graeme , Riley Malcolm , Dwyer Terence 
Published: April 2006

Abstract
There have been no studies of smoking during pregnancy and bone mineralization in children. The objective of this population-based longitudinal study was to determine whether maternal smoking during pregnancy is associated with bone mass and other growth variables in prepubertal children. We studied 330 8-year-old male and female children representing 47% of those who originally took part in a study of risk factors for Sudden Infant Death Syndrome in 1988. The main outcome measures were bone mineral density measured by a Hologic QDR2000 densitometer: birth weight, placental weight, height, and weight. Maternal smoking during pregnancy was associated with deficits in growth with these children having lower height (−1.53 cm, 95% confidence interval [CI] −3.03 to −0.03) and a trend to lower weight (−1.35 kg, 95% CI −2.75 to 0.11) at age 8. Furthermore, there was a disproportionate deficit in bone mass such that those children whose mothers smoked during pregnancy had lower size adjusted bone mass at the lumbar spine (−0.019 g/cm2, 95% CI −0.033 to −0.005) and femoral neck (−0.018 g/cm2, 95%CI −0.034 to −0.002) but not total body (−0.005 g/cm2, 95% CI −0.015 to 0.005). This association was only present for children born at term. Mothers who smoked during pregnancy also had lower placental weight (− 56 g, 95% CI −95 to −17), and further adjustment for placental weight led to nonsignificant results for smoking with both growth and bone parameters, suggesting that these associations may be mediated through placental size and function. Maternal smoking habit in 1996 was not significantly associated with bone mass at any site. In conclusion, this study has demonstrated a long-term negative association between maternal smoking during pregnancy and both growth and bone mass in children born at term, and suggests that the timing of exposure rather than the dose or duration is critical. If these associations are present in other populations and they persist until the attainment of peak bone mass, then our findings suggest that osteoporosis prevention programs should start very early in the life cycle.
Neurokinin-A in Bone and Joint Tissues: Changes in Adjuvant Arthritis
Authors: Elhassan Adlan M. , Lindgren J. U. , Hultenby K. , Adem Abdu 
Published: April 2006

Abstract
The localization of neurokinin A (NK-A) in the normal ankle joint of rats was investigated by an immunoelectron microscopic technique with specific antisera to NK-A. Immunoreactivity was detected in bone matrix, myelinated nerve fiber in the periosteum, and bone marrow and synovial cells. No immunoreactivity was observed in osteoblasts, osteocytes, and osteoclasts. Using radioimmunoassay (RIA), a detectable concentration of NK-A was observed in the bone marrow, periosteum, cortical bone, and ankle of normal rats. In rats with chronic adjuvant arthritis, induced by intradermal injection of mycobacterium butyricum in paraffin oil into the base of the tail, the concentrations of NK-A using RIA in ankles and spinal cords were found to be significantly increased compared with acute or control rats. There were no significant differences between the latter two. Similarly, increased NK-A labeling was observed using immunoelectron microscopy in bone matrix and bone marrow monocyte cells of the chronic arthritic rats. These findings indicate the existence of as well as a biological role of NK-A in bone and joint tissues.
Cartilage-Derived Retinoic Acid–Sensitive Protein and Type II Collagen Expression During Fracture Healing Are Potential Targets for Sox9 Regulation
Authors: Sakano Shinji , Zhu Yong , Sandell Linda J. 
Published: April 2006

Abstract
Cartilage-derived retinoic acid-sensitive protein (CD-RAP) and mRNA were examined in the mouse fracture model by immunohistochemistry and Northern blot analysis and compared with the expression of type II collagen. We also studied the expression of the transcription factor Sox9, reported to enhance type II collagen and CD-RAP gene expression in vitro. CD-RAP was first detected in immature chondrocytes on day 5. Intense signals for CD-RAP were found in fracture cartilage on days 7 and 9. CD-RAP decreased at the phase of endochondral ossification. Throughout fracture healing, CD-RAP was detected in cartilage and not in bone or fibrous tissue, thus CD-RAP may be a molecular marker of cartilage formation during fracture healing. Northern blot analysis revealed similar changes in CD-RAP and type II collagen mRNA levels. However, with respect to protein levels, CD-RAP decreased faster than type II collagen implying the stability is lower than type II collagen. Increased levels of Sox9 mRNA and protein were detected on day 5 and coincided with the initial increase of CD-RAP and type II collagen mRNAs. Sox9 mRNA levels declined with the progress of chondrocyte hypertrophy, followed by a concomitant decrease in CD-RAP and type II collagen mRNA levels. These changes in Sox9 expression compared with the cartilage-specific genes (CD-RAP and type II collagen) suggest that cell differentiation during fracture healing may be controlled by specific transcriptional factors which regulate phenotypic changes of the cells.
Temporal and Spatial Characterization of Regenerate Bone in the Lengthened Rabbit Tibia
Authors: Richards Mark , Goulet James A. , Schaffler Mitchell B. , Goldstein Steven A. 
Published: April 2006

Abstract
A rabbit model of bilateral tibial lengthening was used to investigate temporal and spatial changes in new bone volume and architecture during regenerate bone formation. Tibiae were lengthened 9.0 mm at 0.75 mm/day after a 6-day latency period. Animals were euthanized at four time points, and new bone volume and architecture within the distraction gap were assessed by microcomputed tomography and histomorphometry. New bone formation began before day 18 postsurgery and increased markedly between day 18 (completion of distraction) and day 24. This period of high bone formation activity might therefore be optimal for biologic and mechanical interventions aimed at enhancing bone regeneration. Regions of both endochondral and intramembranous bone formation were observed throughout the consolidation period. Significant increases in bone volume fraction were observed early in the consolidation period and were attributed to significant increases in trabecular thickness. This suggested that increased mineral density in the gap tissue with time was a consequence of increased osteoblast activity and associated trabecular thickening. New bone formation was shown to be highly oriented toward the distraction axis throughout lengthening. More bone formed consistently in lateral and proximal regions of the distraction gap, perhaps due to improved blood supply or progenitor cell availability in these areas. No differences in trabecular architecture were detected between regions having more or less bone volume, suggesting that bony tissue differentiation in all regions of the distraction gap was similar. Homotypical variations in measures of bone architecture were small; thus, these outcome variables seem appropriate for determining the effects of biological and mechanical interventions on bone regeneration in this animal model.
Suggestive Linkage of the Parathyroid Receptor Type 1 to Osteoporosis
Authors: Duncan Emma L. , Brown Matthew A. , Sinsheimer Janet , Bell John , Carr Andrew J. , Wordsworth B. Paul , Wass John A. H. 
Published: April 2006

Abstract
We have investigated the role of 23 candidate genes in the control of bone mineral density (BMD) by linkage studies in families of probands with osteoporosis (lumbar spine [LS] or femoral neck [FN] BMD T score &lt; −2.5) and low BMD relative to an age- and gender-matched cohort (Z score &lt; −2.0). One hundred and fifteen probands (35 male, 80 female) and 499 of their first- or second-degree relatives (223 males and 276 females) were recruited for the study. BMD was measured at the LS and FN using dual-energy X-ray absorptiometry and expressed as age- and gender-matched Z scores corrected for body mass index. The candidate genes studied were the androgen receptor, type I collagen A1 (COLIA1), COLIA2, COLIIA1, vitamin D receptor (VDR), colony-stimulating factor 1, calcium-sensing receptor, epidermal growth factor (EGF), estrogen receptor 1 (ESR1), fibrillin type 1, insulin-like growth factor 1, interleukin-1 alpha (IL-1α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-11 (IL-11), osteopontin, parathyroid hormone (PTH), PTH-related peptide, PTH receptor type 1 (PTHR1), transforming growth factor-beta 1, and tumor necrosis factors alpha and beta. Sixty-four microsatellites lying close to or within these genes were investigated for linkage with BMD. Using the program MapMaker/Sibs there was suggestive evidence of linkage between BMD and PTHR1 (maximum LOD score obtained [MLS] 2.7–3.5). Moderate evidence of linkage was also observed with EGF (MLS 1.8), COLIA1 (MLS 1.7), COLIIA1/VDR (MLS 1.7), ESR1 (MLS 1.4), IL-1α (MLS 1.4), IL-4 (MLS 1.2), and IL-6 (MLS 1.2). Variance components analysis using the program ACT, correcting for proband-wise ascertainment, also showed evidence of linkage (p ≤ 0.05) at markers close to or within the candidate genes IL-1α, PTHR1, IL-6, and COLIIA1/VDR. Further studies will be required to confirm these findings, to refine the location of gene responsible for the observed linkage, and to screen the candidate genes targeted at these loci for mutations.
Alkaline Phosphatase Knock-Out Mice Recapitulate the Metabolic and Skeletal Defects of Infantile Hypophosphatasia
Authors: Fedde Kenton N. , Blair Libby , Silverstein Julie , Coburn Stephen P. , Ryan Lawrence M. , Weinstein Robert S. , Waymire Katrina , Narisawa Sonoko , Millán José L. , Macgregor Grant R. , Whyte Michael P. 
Published: April 2006

Abstract
Hypophosphatasia is an inborn error of metabolism characterized by deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP) and skeletal disease due to impaired mineralization of cartilage and bone matrix. We investigated two independently generated TNSALP gene knock-out mouse strains as potential models for hypophosphatasia. Homozygous mice (–/–) had &lt; 1% of wild-type plasma TNSALP activity; heterozygotes had the predicted mean of ∼50%. Phosphoethanolamine, inorganic pyrophosphate, and pyridoxal 5′-phosphate are putative natural substrates for TNSALP and all were increased endogenously in the knock-out mice. Skeletal disease first appeared radiographically at ∼10 days of age and featured worsening rachitic changes, osteopenia, and fracture. Histologic studies revealed developmental arrest of chondrocyte differentiation in epiphyses and in growth plates with diminished or absent hypertrophic zones. Progressive osteoidosis from defective skeletal matrix mineralization was noted but not associated with features of secondary hyperparathyroidism. Plasma and urine calcium and phosphate levels were unremarkable. Our findings demonstrate that TNSALP knock-out mice are a good model for the infantile form of hypophosphatasia and provide compelling evidence for an important role for TNSALP in postnatal development and mineralization of the murine skeleton.
Fluid Shear Stress Increases Interleukin-11 Expression in Human Osteoblast-like Cells: Its Role in Osteoclast Induction
Authors: Sakai Kenji , Mohtai Masaaki , Shida Jun-Ichi , Harimaya Katsumi , Benvenuti Susanna , Brandi Maria L. , Kukita Toshio , Iwamoto Yukihide 
Published: April 2006

Abstract
It is unclear how mechanical stress influences bone cells. Mechanical stress causes fluid shear stress (FSS) in the bone. Osteoblast lineage cells are thought to sense FSS and regulate bone remodeling. We therefore investigated the effects of FSS on human osteoblast-like osteosarcoma cells: SaOS-2 cells in vitro. The conditioned medium of the SaOS-2 cells after 24 h of FSS (24 h-FSS CM) showed such osteoclastic phenotype inductions as significantly increasing the number of tartrate-resistant acid phosphatase (TRAP) positive multinuclear cells in rat bone marrow cells and TRAP-positive cells in human preosteoclastic cells: FLG 29.1 cells. An enzyme-linked immunosorbent assay showed interleukin-11 (IL-11) protein to increase 7-fold in the 24 h-FSS CM. A Northern analysis showed that IL-11 mRNA increased 4-fold in the SaOS-2 cells after 6 h-FSS; however, no IL-6 mRNA expression was detected. Furthermore, the anti-human IL-11 antibody significantly neutralized the osteoclastic phenotype induction of the 24 h-FSS CM. The IL-11 mRNA up-regulation in SaOS-2 cells by the 6 h-FSS was not inhibited by the anti-human transforming growth factor-β1 antibody, but it was significantly inhibited by indomethacin. An enzymeimmunoassay showed prostaglandin E2 to increase 7-fold in the 1 h-FSS CM. These findings thus suggest that FSS induces osteoblasts to produce IL-11 (mediated by prostaglandins) and thus stimulates bone remodeling.
Bone Mineral Density Testing and Osteoporosis Education Improve Lifestyle Behaviors in Premenopausal Women: A Prospective Study
Authors: Jamal Sophie A. , Ridout Rowena , Chase Cheryl , Fielding Lynda , Rubin Laurence A. , Hawker Gillian A. 
Published: April 2006

Abstract
One way to decrease the risk of osteoporosis is to maximize peak bone mass. Peak bone mass may be moderately influenced by lifestyle behaviors: increasing calcium and exercise, decreasing alcohol intake and smoking may increase peak bone mass. We examined the effects of osteoporosis education and bone mineral density (BMD) testing on self-reported lifestyle behaviors in 669 premenopausal women enrolled in a prospective study to assess determinants of peak bone mass. Study participants completed a questionnaire that assessed lifestyle behaviors, received pamphlets about osteoporosis, and had BMD testing. One year later, the women completed a similar questionnaire. After education about osteoporosis and BMD testing, women reported that they were less likely to smoke (odds ratio [OR] = 0.55; 95% confidence interval [95% CI]: 0.28–1.0), consume alcohol (OR = 0.13; 95% CI: 0.04–0.34), and caffeinated beverages (OR = 0.43; 95% CI: 0.27–0.68). Women were more likely to use calcium supplements (OR = 4.3; 95% CI: 3.04–6.2), vitamin D supplements (OR = 12.6; 95% CI: 7.4–22.9), and drink at least one glass of milk a day (OR = 13.3; 95% CI: 7.8–23.9). Further, women with low bone mass were more likely to use calcium supplements (OR = 1.7; 95% CI: 1.2–2.3) and vitamin D supplements (OR = 1.6; 95% CI: 1.1–2.2) compared with women who had normal bone mass. Thus, our intervention improved self-reported lifestyle behaviors in premenopausal women. Such behaviors may ultimately increase peak bone mass and decrease the risk of developing osteoporosis.
Growing C57Bl/6 Mice Increase Whole Bone Mechanical Properties by Increasing Geometric and Material Properties
Authors: Brodt Michael D. , Ellis Cara B. , Silva Matthew J. 
Published: April 2006

Abstract
In vivo murine models are becoming increasingly important in bone research. To establish baseline data for researchers using these models, we studied the long bones from C57BL/6 female mice, a strain that is widely used in bone research. We determined the femoral structural and material properties in both torsion and four-point bending for mice at ages 4–24 weeks. Measurements of femoral cross-sectional geometry and tibial densitometric properties were also obtained. Results indicated that all structural properties (except ultimate energy), changed significantly with age (p &lt; 0.001). Ultimate torque, ultimate moment, torsional rigidity, and bending rigidity all increased to peak values at 20 weeks, whereas ultimate rotation and ultimate displacement decreased to minimum values at 20 weeks. Our data indicate that increases in the material properties contributed more than increases in cross-sectional geometry to the changes in structural rigidity and ultimate load. For example, from 4–20 weeks torsional rigidity increased 1030%, while shear modulus increased 610% and the polar moment of inertia (a measure of the geometric resistance to rotation) increased by only 85%. Changes in the cross-sectional geometry with age were due to increases in periosteal diameter and decreases in endosteal diameter. In general, both torsion and bending techniques revealed large changes in structural and material properties with age. We conclude that peak bone strength is not achieved before 20 weeks in C57BL/6 female mice, and that torsion and four-point bending tests are equally well suited for evaluating mechanical properties of murine long bones.
Molecular Characterization of the α1 Subunit of the L Type Voltage Calcium Channel Expressed in Rat Calvarial Osteoblasts
Authors: Loza Juan C. , Carpio Lillian C. , Bradford Peter G. , Dziak Rosemary 
Published: April 2006

Abstract
Voltage-activated calcium channels (VACCs) regulate extracellular calcium influx in many cells. VACCs are composed of five subunits. The α1 subunit is considered the most important in regulating channel function. Three isoforms of this subunit have been described: skeletal, cardiac, and neuroendocrine. It was the purpose of the present study to determine the molecular identity of the α1 subunit of the VACCs in rat calvarial osteoblasts and to study the nature of the regulation of these channels as a function of cellular growth. We also attempted to identify which isoform of the α1 subunit of the VACCs mediates the effects of epidermal growth factor (EGF) on osteoblastic cell proliferation. Reverse transcription-polymerase chain reaction was used to detect the isoforms of the VACCs that are expressed in osteoblastic cells. These analyses showed that the proliferative state of the cell and the time in culture influence RNA expression. The only α1 subunit detected in osteoblasts corresponds to the cardiac isoform. In additional experiments, the effects of EGF on cytosolic calcium and osteoblast proliferation were determined. For these experiments, the synthesis of the different isoforms of the VACCs was selectively blocked by antisense oligonucleotides prior to EGF stimulation. These studies showed that the cardiac isoform mediates the effects of EGF on cytosolic calcium and cellular proliferation in rat calvarial osteoblasts.
Cloning of a 2.5 kb Murine Bone Sialoprotein Promoter Fragment and Functional Analysis of Putative Osf2 Binding Sites
Authors: Benson M. Douglas , Aubin Jane E. , Xiao Guozhi , Thomas Peedikayil E. , Dr. Franceschi Renny T. 
Published: April 2006

Abstract
Bone sialoprotein (BSP) is an extracellular matrix protein that is intimately associated with the process of biomineralization. Osf2, a member of the Cbf/runt family of transcription factors, is required for the development of osteoblasts in vivo and has been reported to stimulate the transcription of BSP when overexpressed in mesenchymal cell lines. To investigate the role of Osf2 in BSP expression, we cloned a 2.5 kb fragment of a 5′ untranscribed sequence from the murine BSP gene and evaluated it for putative Osf2 binding sites. This promoter, which was able to direct 5- to 10-fold higher levels of luciferase reporter expression in osteoblastic cells than in nonbone cell lines, contains two consensus core binding sites for members of the Cbf/runt family. One, at –61 relative to the start of transcription, is within a region having 75% overall sequence identity with the rat and human BSP promoters. The other is located at −1335, outside this highly conserved region. Neither site is completely conserved in the rat or human sequences. Only the −1335 site was able to bind a protein in nuclear extracts of osteoblastic cells, and this protein was identified as Osf2. Despite this in vitro binding ability, we detected no significant enhancer activity in the −1335 element when placed in front of a minimal osteocalcin promoter driving a luciferase reporter gene in osteoblastic cells nor any loss in transcriptional activity of a 5′ promoter deletion which eliminated this element as compared with the full-length 2.5 kb promoter. These results suggest that Osf2 binding to the BSP promoter is not essential for its osteoblast-selective expression.
The Parathyroid Hormone–Related Protein (PTHrP) Gene: Use of Downstream TATA Promotor and PTHrP 1–139 Coding Pathways in Primary Breast Cancers Vary with the Occurrence of Bone Metastasis
Authors: Dr. Bouizar Zhor , Spyratos Frederique , De vernejoul Marie-Christine 
Published: April 2006

Abstract
We analyzed the use of different promoters and the splicing patterns of the exons encoding 5′- and 3′-untranslated sequence amounts of parathyroid hormone–related protein (PTHrP) gene products in breast cancers. Tumor samples from 74 cases of primary breast cancer that had been followed from 1 to 14 years were selected retrospectively according to the occurrence of metastasis: 18 patients developed no metastasis (NM), 56 developed metastases (M), 22 of whom developed metastases in soft tissues (MB−) and 34 of whom developed bone metastases (MB+). The amount of the 1–139 isoform mRNA was much higher in the tumors of patients who later developed metastases (M: 0.29 ± 0.03) than in those of patients who developed no metastases (NM, 0.13 ± 0.03; p &lt; 0.01). This isoform mRNA was also more abundant in breast tumors from patients who developed bone metastases (MB+, 0.39 ± 0.04) than in those of patients who developed metastases in soft tissues (MB−, 0.15 ± 0.03; p &lt; 0.0001). By contrast, the amounts of the 1–141 isoform mRNA in these three groups of tumors were similar, but its concentration was higher in the tumors of premenopausal women than in those of postmenopausal women (p &lt; 0.05). Analysis with 5′ untranslated regions-specific primers showed transcription from all three putative transcription start sites of PTHrP (P1, P2, and P3). The P3-initiated transcripts were more abundant in patients who developed metastases (M, 0.31 ± 0.03) than in the nonmetastatic tumors (NM, 0.13 ± 0.03; p &lt; 0.01). The amount of P3 element did not differ with the site of metastasis (BM+, 0.32 ± 0.05; BM−, 0.28 ± 0.05; NS). The same trend was observed for the P2 element. However, the use of P2-initiated messages was strongly associated with the absence of estrogen receptors from the breast tumors (p &lt; 0.01). We thus find a close association between the pattern of PTHrP gene expression and the outcome of breast cancer. The P3-initiated start site and the presence of PTHrP 139 mRNA could help identify patients at risk of developing metastases.