bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-Level Cadmium Exposure and Osteoporosis
Authors: Alfvén Tobias , Elinder Carl-Gustaf , Carlsson Margareta Dea , Grubb Anders , Hellström Lennart , Persson Bodil , Pettersson Conny , Spång Gunnar , Schütz Andrejs , Järup Lars 
Published: April 2006

Abstract
Osteoporosis is a major cause of morbidity worldwide. A number of risk factors, such as age and gender, are well established. High cadmium exposure causes renal damage and in severe cases also causes osteoporosis and osteomalacia. We have examined whether long-term low-level cadmium exposure increases the risk of osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men and 544 women, aged 16–81 years, environmentally or occupationally exposed to cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine was used as the dose estimate and protein HC was used as a marker of renal tubular damage. There was a clear dose-response relation between cadmium dose and the prevalence of tubular proteinuria. Inverse relations were found between cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over 60 years of age. There was a dose-response relation between cadmium dose and osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose category (≥3 nmol/mmol creatinine) compared with the lowest dose group (&lt;0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose group 0.5-3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of cadmium is associated with an increased risk of osteoporosis.
Osteogenesis from Cultured Chick Periostea Has a Specific Requirement for Chloride
Authors: Lovitch Dinah , Christianson Michael L. 
Published: April 2006

Abstract
Bone development, like embryonic development in general, depends on a particular internal electrical milieu. Ions are the carriers of currents that maintain this internal environment. In embryonic bone, chloride is a major carrier of such current. To explore the role chloride plays in embryonic bone development we performed several ion-removal experiments, using the chick periosteal osteogenesis (CPO) system as our model. We found that if chloride is reduced in the medium and replaced with a nontoxic anion, alkaline phosphatase (ALP) activity does not rise, nor does osteogenic development occur. However, acid phosphatase (AP) activity is not affected by level of chloride. Experiments using metabolic inhibitors showed that explants cultured in low chloride medium remain viable. Dose-response studies revealed that the response of ALP activity to chloride concentration is sigmoidal, with a [Cl−]0.5 of 45.9 mM. Reciprocal transfers of explants between complete and low chloride medium show that the rise in ALP activity depends on the length of time explants are cultured with chloride. In contrast, such transfer experiments show that osteogenesis requires chloride only during days 2–3 of culture.
Particulate Wear Debris Activates Protein Tyrosine Kinases and Nuclear Factor κB, Which Down-Regulates Type I Collagen Synthesis in Human Osteoblasts
Authors: Vermes Csaba , Roebuck Kenneth A. , Chandrasekaran Raman , Dobai József G. , Jacobs Joshua J. , Glant Tibor T. 
Published: April 2006

Abstract
Particulate wear debris generated mechanically from prosthetic materials is phagocytosed by a variety of cell types within the periprosthetic space including osteoblasts, which cells with an altered function may contribute to periprosthetic osteolysis. Exposure of osteoblast-like osteosarcoma cells or bone marrow-derived primary osteoblasts to either metallic or polymeric particles of phagocytosable sizes resulted in a marked decrease in the steady-state messenger RNA (mRNA) levels of procollagen α1[I] and procollagen α1[III]. In contrast, no significant effect was observed for the osteoblast-specific genes, such as osteonectin and osteocalcin (OC). In kinetic studies, particles once phagocytosed, maintained a significant suppressive effect on collagen gene expression and type I collagen synthesis for up to five passages. Large particles of a size that cannot be phagocytosed also down-regulated collagen gene expression suggesting that an initial contact between cells and particles can generate gene responsive signals independently of the phagocytosis process. Concerning such signaling, titanium particles rapidly increased protein tyrosine phosphorylation and nuclear transcription factor κB (NF-κB) binding activity before the phagocytosis of particles. Protein tyrosine kinase (PTK) inhibitors such as genistein and the NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly reduced the suppressive effect of titanium on collagen gene expression suggesting particles suppress collagen gene expression through the NF-κB signaling pathway. These results provide a mechanism by which particulate wear debris can antagonize the transcription of the procollagen α1[I] gene in osteoblasts, which may contribute to reduced bone formation and progressive periprosthetic osteolysis.
Importance of Membrane- or Matrix-Associated Forms of M-CSF and RANKL/ODF in Osteoclastogenesis Supported by SaOS-4/3 Cells Expressing Recombinant PTH/PTHrP Receptors
Authors: Itoh Kanami , Udagawa Nobuyuki , Matsuzaki Kenichiro , Takami Masamichi , Amano Hitoshi , Shinki Toshimasa , Ueno Yutaka , Takahashi Naoyuki , Suda Tatsuo 
Published: April 2006

Abstract
SaOS-4/3, a subclone of the human osteosarcoma cell line SaOS-2, established by transfecting the human parathyroid hormone/parathyroid hormone-related protein (PTH/PTHrP) receptor complementary DNA (cDNA), supported osteoclast formation in response to PTH in coculture with mouse bone marrow cells. Osteoclast formation supported by SaOS-4/3 cells was completely inhibited by adding either osteoprotegerin (OPG) or antibodies against human macrophage colony-stimulating factor (M-CSF). Expression of messenger RNAs (mRNAs) for receptor activator of NF-κB ligand/osteoclast differentiation factor (RANKL/ODF) and both membrane-associated and secreted forms of M-CSF by SaOS-4/3 cells was up-regulated in response to PTH. SaOS-4/3 cells constitutively expressed OPG mRNA, expression of which was down-regulated by PTH. To elucidate the mechanism of PTH-induced osteoclastogenesis, SaOS-4/3 cells were spot-cultured for 2 h in the center of a culture well and then mouse bone marrow cells were uniformly plated over the well. When the spot coculture was treated for 6 days with both PTH and M-CSF, osteoclasts were induced exclusively inside the colony of SaOS-4/3 cells. Osteoclasts were formed both inside and outside the colony of SaOS-4/3 cells in coculture treated with a soluble form of RANKL/ODF (sRANKL/sODF) in the presence of M-CSF. When the spot coculture was treated with sRANKL/sODF, osteoclasts were formed only inside the colony of SaOS-4/3 cells. Adding M-CSF alone failed to support osteoclast formation in the spot coculture. PTH-induced osteoclast formation occurring inside the colony of SaOS-4/3 cells was not affected by the concentration of M-CSF in the culture medium. Mouse primary osteoblasts supported osteoclast formation in a similar fashion to SaOS-4/3 cells. These findings suggest that the up-regulation of RANKL/ODF expression is an essential step for PTH-induced osteoclastogenesis, and membrane- or matrix-associated forms of both M-CSF and RANKL/ODF are essentially involved in osteoclast formation supported by osteoblasts/stromal cells.
Retracted: Effect of Deconditioning on Cortical and Cancellous Bone Growth in the Exercise Trained Young Rats
Authors: Iwamoto Jun , Yeh James K. , Aloia John F. 
Published: April 2006

Abstract
Exercise enhances bone growth and increases peak bone mass. The aim of this study was to determine whether or not 4 weeks of deconditioning after 8 weeks of exercise in growing rats would result in a decrease in bone gain or reverse the benefits of exercise. Fifty 4-week-old female Sprague-Dawley rats were randomized by a stratified weight method into 5 groups with 10 rats in each group: 8 weeks exercise (8EX), 8 weeks sedentary control (8S), 12 weeks exercise (12EX), 8 weeks exercise followed by 4 weeks sedentary (8EX4S), and 12 weeks sedentary control (12S). The exercise consisted of running on a treadmill with a 5° slope at 24 m/minute for 1 h/day and 5 days/week. After each period of exercise, cancellous and cortical bone histomorphometry were performed on double fluorescent labeled 5-μm-thick sections of the proximal tibia and 40-μm-thick sections of the tibial shaft, respectively. Eight and 12 weeks of exercise resulted in a significant increase in the body weight and gastrocnemius muscle weight by two-way analysis of variance (ANOVA). The femoral wet weight (mg; mean ± SD; 8EX, 781 ± 45.1 vs. 8S, 713 ± 40.5; p &lt; 0.05; 12EX, 892 ± 41.6 vs. 12S, 807 ± 19.8; p &lt; 0.05) was significantly higher in the exercise group than that in the respective control groups. The femoral wet weight and bone volume (BV) of the 8EX4S group (818 ± 46.2 mg and 531 ± 31.2 μl, respectively) were significantly lower than those of the 12EX group (p &lt; 0.05) and did not differ significantly from those of the 12S groups. The cancellous BV was significantly higher in the 8EX and 12EX groups than that in the respective sedentary groups (p &lt; 0.05). The cortical bone area of the tibial shaft was also significantly higher in the 12EX than that in the 12S group (p &lt; 0.05). The increase in the cancellous BV or cortical bone area was caused by an increase in the mineral apposition rate (MAR), without a significant effect in the labeled perimeter. The bone formation rate (BFR; μm3/μm2 per day) in the cancellous bone (12EX, 27.9 ± 7.74 vs. 12S, 15.4 ± 4.56; p &lt; 0.05) or periosteal surface (12EX, 127.6 ± 27.7 vs. 12S, 79.5 ± 18.6; p &lt; 0.05) was significantly higher in the exercised groups than that in the respective control group (p &lt; 0.05). Again, deconditioning resulted in a decrease in the cancellous BFR, BV, periosteal BFR, and cortical bone area to levels not significantly different from the 12S group. In conclusion, our findings showed that exercised growing rats, when deconditioned, lost the benefits gained through exercise and their bone parameters were reduced to levels not different from the sedentary control. Thus, continued exercise is required to maintain high bone mass.
Reconciling Quantitative Ultrasound of the Calcaneus with X-Ray-Based Measurements of the Central Skeleton
Authors: Ayers Michael , Prince Michelle , Ahmadi Sadri , Baran Daniel T. 
Published: April 2006

Abstract
Osteoporosis is frequently undiagnosed before fracture because of the lack of availability of instruments to quantitate bone mass. To evaluate the utility of quantitative ultrasound (QUS) of the calcaneus to diagnose osteoporosis, we determined bone mineral density (BMD) of the posterior-arterior spine, total hip, and femoral neck by dual-energy X-ray absorptiometry (DXA) and QUS in 312 women aged 50 years and older. A risk factor assessment (simple calculated osteoporosis risk estimation [SCORE]) also was quantitated in all women. Ninety-four of the 312 women were diagnosed as osteoporotic based on T scores ≤ −2.5 at the spine, total hip, and/or femoral neck. The sensitivity of the individual central sites for the diagnosis of osteoporosis was 49% at the spine (46 of 94 women), 32% at the total hip (30 of 94 women), and 81% at the femoral neck (76 of 94 women). At a QUS T score ≤ −1, the peripheral technique had a sensitivity of 62% and a specificity of 72%. Combining a QUS T score of ≤ −1 followed by a risk factor assessment of women with a QUS T score ≥ −0.99 using a cut point of 11 increased sensitivity to 81% (comparable with femoral neck DXA) but decreased specificity to 58%. If peripheral QUS measurements and risk factor assessment are the only tools employed before initiation of therapy, the benefits of increased ease of diagnosis will need to be balanced against potentially unnecessary treatment in some normal patients and lack of treatment in some osteoporotic patients.
Cloning and Functional Analysis of a Family of Nuclear Matrix Transcription Factors (NP/NMP4) that Regulate Type I Collagen Expression in Osteoblasts
Authors: Thunyakitpisal Pasutha , Alvarez Marta , Tokunaga Kunihiko , Onyia Jude E. , Hock Janet , Ohashi Naoko , Feister Hilary , Rhodes Simon J. , Bidwell Joseph P. 
Published: April 2006

Abstract
Collagen expression is coupled to cell structure in connective tissue. We propose that nuclear matrix architectural transcription factors link cell shape with collagen promoter geometry and activity. We previously indicated that nuclear matrix proteins (NP/NMP4) interact with the rat type I collagen α1(I) polypeptide chain (COL1A1) promoter at two poly(dT) sequences (sites A and B) and bend the DNA. Here, our objective was to determine whether NP/NMP4-COL1A1 binding influences promoter activity and to clone NP/NMP4. Promoter-reporter constructs containing 3.5 kilobases (kb) of COL1A1 5′ flanking sequence were fused to a reporter gene. Mutation of site A or site B increased promoter activity in rat UMR-106 osteoblast-like cells. Several full-length complementary DNAs (cDNAs) were isolated from an expression library using site B as a probe. These clones expressed proteins with molecular weights and COL1A1 binding activity similar to NP/NMP4. Antibodies to these proteins disrupted native NP/NMP4-COL1A1 binding activity. Overexpression of specific clones in UMR-106 cells repressed COL1A1 promoter activity. The isolated cDNAs encode isoforms of Cys2His2 zinc finger proteins that contain an AT-hook, a motif found in architectural transcription factors. Some of these isoforms recently have been identified as Cas-interacting zinc finger proteins (CIZ) that localize to fibroblast focal adhesions and enhance metalloproteinase gene expression. We observed NP/NMP4/CIZ expression in osteocytes, osteoblasts, and chondrocytes in rat bone. We conclude that NP/NMP4/CIZ is a novel family of nuclear matrix transcription factors that may be part of a general mechanical pathway that couples cell structure and function during extracellular matrix remodeling.
Fracture Site-Specific Deficits in Bone Size and Volumetric Density in Men with Spine or Hip Fractures
Authors: Seeman Ego , Duan Yunbo , Fong Christopher , Edmonds Jan 
Published: April 2006

Abstract
To study the structural basis of bone fragility in men, we compared bone size and volumetric bone mineral density (vBMD) of the third lumbar vertebra and femoral neck in 95 men with spine fractures, 127 men with hip fractures, and 395 healthy controls using dual-energy X-ray absorptiometry (DXA). The results were expressed in absolute terms and age-specific SD scores (mean ± SEM). In controls, vertebral body and femoral neck width increased across age, being 0.46 ± 0.11 SD and 0.91 ± 0.08 SD higher in elderly men than in young men, respectively (both, p &lt; 0.001). Men with spine fractures had reduced vertebral body width (−0.45 ± 0.10 SD; p &lt; 0.01) but not femoral neck width (−0.15 ± 0.10 SD, NS). Men with hip fractures had reduced femoral neck width (−0.45 ± 0.11 SD; p &lt; 0.01) and vertebral body width (−0.25 ± 0.10 SD; p &lt; 0.05). The deficits in bone volume (BV) exaggerated the deficits in bone mineral content (BMC) by 40% at the vertebrae in men with spine fractures and by 9% at the femoral neck in men with hip fractures. vBMD deficits were greater at the vertebrae in men with spine fractures than in men with hip fractures (−1.37 ± 0.08 SD vs.−0.70 ± 0.10 SD, respectively; p &lt; 0.01) but were similar at the femoral neck (−0.93 ± 0.10 SD and −0.76 ± 0.11 SD, respectively, NS), despite the men with spine fracture being 10 years younger. Bone fragility leading to spine or hip fractures in men may be the result of fracture site-specific deficits in bone size and vBMD that have their origins in growth, aging, or both.
Estrogen Receptor α Gene Polymorphisms and Bone Mineral Density: Haplotype Analysis in Women from the United Kingdom
Authors: Albagha Omar M. E. , McGuigan Fiona E. A. , Reid David M. , Ralston Stuart H. 
Published: April 2006

Abstract
Genetic factors are important in the pathogenesis of osteoporosis and the estrogen receptor has been suggested as a possible candidate gene for regulation of bone mineral density (BMD). We investigated the relationship between PvuII, XbaI, and dinucleotide (TA)n repeat polymorphisms of the estrogen receptor α (ER-α) gene and BMD in a study of women from northeast Scotland in the United Kingdom. No significant association was observed between BMD values at the lumbar spine (LS) and femoral neck (FN) in relation to PvuII and XbaI polymorphisms individually, but haplotype analysis showed that BMD values (Z score) were significantly lower in those who carried the Px haplotype (n = 36) compared with those who did not (n = 170) at both the LS (mean ± SEM; −0.775 ± 0.125 vs. −0.285 ± 0.082; p = 0.002) and the FN (−0.888 ± 0.130 vs. −0.335 ± 0.083; p = 0.0006). In keeping with this, the Px haplotype also was found to be an independent predictor of LS BMD (p = 0.019) and FN BMD (p = 0.005) in a multiple regression analysis model that included other possible predictors of BMD including age, years since menopause (YSM), hormone-replacement therapy (HRT) use, weight, and height. This model explained 15.7% and 23.4% of the total observed variance in LS and FN BMD, respectively, with the Px haplotype accounting for ∼3% of the variance at both sites. Although the TA repeat polymorphism was in strong linkage disequilibrium (LD) with the PvuII (χ2 = 109.8; p &lt; 0.0001) and XbaI (χ2 = 97.2; p &lt; 0.0001) polymorphisms, there was no overall association between TA repeat number and BMD. We conclude that polymorphisms of the ER-α gene are significantly related to BMD in our population and that this association is dependent on the Px haplotype, suggesting that it is the Px haplotype, or a linked polymorphism, that confers risk.
The Unique Tryptophan Residue of the Vitamin D Receptor Is Critical for Ligand Binding and Transcriptional Activation
Authors: Solomon Cynthia , Macoritto Michael , Gao Xiao-Ling , White John H. , Kremer Richard 
Published: April 2006

Abstract
The human vitamin D receptor (hVDR) is a member of the nuclear receptor superfamily of transcriptional regulators. Here we show that tryptophan 286 of the hVDR is critical for ligand binding and transactivation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] target genes. Two mutants of the hVDR were produced, W286A and W286F, in which the tryptophan was replaced with an alanine or a phenylalanine, respectively. The W286A mutant did not bind 1,25(OH)2D3, interact with steroid receptor coactivator 1 (SRC-1) in vitro, or activate transcription. Moreover, the W286A receptor did not heterodimerize in a ligand-dependent manner with the human retinoid X receptor α (hRXRα). Although the W286F receptor heterodimerized with hRXRα, interacted with SRC-1, and bound 1,25(OH)2D3, its capacity to transactivate was attenuated severely. Thus, tryptophan 286 of hVDR plays an important role in specific 1,25(OH)2D3 ligand interaction and subsequently in hVDR/RXR interaction, SRC-1 binding, and ligand-dependent transactivation of 1,25(OH)2D3 target genes. These results identify the first amino acid that is absolutely required for ligand binding in the VDR and further define the structure-function relationship of 1,25(OH)2D3 interaction with its receptor.
25-Hydroxyvitamin D 1α-Hydroxylase: Structure of the Mouse Gene, Chromosomal Assignment, and Developmental Expression
Authors: Panda Dibyendu K. , Kawas Sausan Al , Seldin Michael F. , Hendy Geoffrey N. , Goltzman David 
Published: April 2006

Abstract
The murine homologue of the 25-hydroxyvitamin D [25(OH)D] 1α-hydroxylase gene [1α(OH)ase; Cyp27b1], which is mutated in humans with vitamin D-dependent rickets type I (VDDR-I; also known as pseudovitamin D-deficiency rickets [PDDR]) was cloned and characterized. Like the human, the mouse gene has nine exons, and the exon-intron organization is well conserved. By interspecific backcross analysis, the Cyp27b1 gene was mapped to 70.5 cM on mouse Chr 10. This is in a region syntenic with human Chr 12q13.1-q13.3 to which the human 1α(OH)ase gene was previously mapped. Kidney expression of the 1α(OH)ase was localized to cortical tubules and was higher in the adult mouse than in the fetus, consistent with the increased role of its product as a circulating hormone postnatally. Prenatally, the 1α(OH)ase gene, together with the vitamin D receptor (VDR) gene, was expressed in embryonic stem cells, and expression of 1α(OH)ase in bone and intestine was higher in the fetus than in the adult. These observations suggest that 1,25-dihydroxyvitamin D [1,25(OH)2D] plays a role in fetal development. In view of the fact that humans lacking 1α(OH)ase have apparently normal prenatal development, this may point to functional redundancy in the fetal vitamin D system, which now can be explored further in mouse models in which the 1α(OH)ase gene has been deleted.
High-Turnover Periprosthetic Bone Remodeling and Immature Bone Formation Around Loose Cemented Total Hip Joints
Authors: Takagi Michiaki , Santavirta Seppo , Ida Hideo , Ishii Masaji , Takei Isao , Niissalo Sirkku , Ogino Toshihiko , Konttinen Yrjö T. 
Published: April 2006

Abstract
Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p &lt; 0.001) and osteoid width (p &lt; 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.