bluuebunny/crossref_metadata_2025_split huggingface dataset:
Articular Chondrocytes Produce Factors That Inhibit Maturation of Sternal Chondrocytes in Serum-Free Agarose Cultures: A TGF-β Independent Process
Authors: D'Angelo Marina , Pacifici Maurizio 
Published: April 2006

Abstract
Under normal conditions, articular chondrocytes persist throughout postnatal life, whereas “transient” chondrocytes, which constitute the bulk of prenatal and early postnatal cartilaginous skeleton, undergo maturation, hypertrophy, and replacement by bone cells. The mechanisms regulating the markedly different behavior and fate of articular and transient chondrocytes are largely unclear. In the present study, we asked whether articular chondrocytes possess dominant antimaturation properties which may subtend their ability to persist throughout life. Adult chicken articular chondrocytes and transient maturing chondrocytes from the core region of day 17 chick embryo cephalic sternum were cultured or cocultured in serum-free agarose conditions. When the sternal cells were grown by themselves, they quickly developed into hypertrophic type X collagen-synthesizing cells; however, when they were cocultured with as few as 10% articular chondrocytes or fed with articular chondrocyte-conditioned medium, their maturation was markedly impaired, as revealed by a sharp drop in type X collagen synthesis. A similar, albeit less potent, antimaturation activity characterized resting and proliferating immature chondrocytes isolated from other regions of embryonic sternum. Transforming growth factor-β2 (TGF-β2) was previously suggested to be an inhibitor of chondrocyte maturation. We found, however, that treatment with a neutralizing antiserum to TGF-β did not counteract the inhibition of maturation in cocultures of articular and maturing core sternal chondrocytes. Indeed, articular chondrocytes produced and accumulated relatively low levels of TGF-β in their culture medium, about 15 ng/ml/48 h, of which over 90% was latent; surprisingly, maturing sternal core chondrocytes accumulated over 10-fold more TGF-β in the medium, about 150 ng/ml/48 h, of which over 20% was endogenously active. These results indicate that articular chondrocytes do possess dominant antimaturation properties which appear to be TGF-β independent. The TGF-βs may thus have a more prominent role in the terminal phases of chondrocyte maturation, as indicated by their abundance and greater activity in hypertrophic chondrocytes.
Association of Bone Mineral Density with Apolipoprotein E Phenotype
Authors: Shiraki Masataka , Shiraki Yumiko , Aoki Choju , Hosoi Takayuki , Inoue Satoshi , Kaneki Masao , Ouchi Yasuyoshi 
Published: April 2006

Abstract
The phenotypes of apolipoprotein E (Apo E) and their relationship with the bone mineral density (BMD) were examined in 284 unrelated postmenopausal Japanese women aged 47–82 years (64.0 ± 1.0 years, mean ± SE). The Apo E phenotype was analyzed by the isoelectric focusing method, followed by immunoblotting. The relationship between the Apo E phenotype and the vitamin D receptor (VDR) gene or estrogen receptor (ER) gene genotypes was also studied in the same population. The Apo E phenotypic frequencies in our population were 9.9% for E3/2, 66.5% for E3/3, 1.8% for E4/2, 19.7% for E4/3, and 2.1% for E4/4. We classified these phenotypes into three categories: Apo E4−/− (E3/2 and E3/3, n = 217), Apo E4+/− (E4/3 and E4/2, n = 61), and Apo E4+/+ (E4/4, n = 6). The age, body weight, body height, and years since menopause were not significantly different among these three categories. The lumbar BMD values in these three groups were significantly different in the order of E4−/− (0.91 ± 0.01 g/cm2), E4+/− (0.85 ± 0.02 g/cm2), and E4+/+ (0.83 ± 0.06 g/cm2) (p = 0.031). The same trend was also observed for the Z score of the total BMD (p = 0.022). The serum level of intact osteocalcin in E4+/+ (15.2 ± 5.7 ng/ml) was higher than in E4−/− (7.7 ± 0.3 ng/ml) or E4+/− (7.7 ± 0.7 ng/ml) (p = 0.004 by analysis of variance). However, there were no other significant differences in the serum or urinary levels of bone turnover markers. Serum cholesterol in the E4+/+ group tended to be higher than in the other two groups (p = 0.05). There were no significant associations of the VDR and ER genotypes with the Apo E4 phenotype. A multivariate linear regression analysis revealed Apo E4 to be a significant, independent predictor of the Z score of the lumbar BMD. The effect of the Apo E4 allele on the Z score of the lumbar BMD (−0.493 ± 0.152) was not significantly different from that in the AAB of VDR (−0.616 ± 0.225) or PPxx of ER (−0.785 ± 0.314). In conclusion, the Apo E4 allele is associated with a low bone mass in postmenopausal Japanese.
Vitamin D Receptor Gene Polymorphisms, Bone Turnover, and Rates of Bone Loss in Older African-American Women
Authors: Zmuda Joseph M. , Cauley Jane A. , Danielson Michelle E. , Wolf Randi L. , Ferrell Robert E. 
Published: April 2006

Abstract
Bone mineral density (BMD) is under genetic control. Some studies in Caucasian and Asian women suggest that polymorphisms in the vitamin D receptor (VDR) gene are associated with BMD and the rate of postmenopausal bone loss. We determined if similar associations exist in 101 African-American women aged 65 years and older (71 ± 5 years, mean ± SD). We also examined the relation between VDR genotype and fractional45Ca absorption and markers of bone formation (osteocalcin) and resorption (N-telopeptides) in these women. BMD was measured at the proximal femur and whole body at baseline and after 1.9 ± 0.4 years (femur only) on a Hologic QDR-2000 densitometer using dual-energy X-ray absorptiometry. Calcaneal BMD was measured with single x-ray absorptiometry. VDR gene polymorphisms were defined by the endonucleases BsmI, ApaI, and TaqI. These polymorphisms were not associated with BMD at any skeletal site or with markers of bone turnover. There was a significant interaction between age and VDR genotype where the oldest women (&gt;70 years) with the tt genotype experienced greater hip bone loss than women with the TT genotype (−2.1%/year vs. −0.4%/year, respectively), whereas heterozygous women experienced an intermediate rate of bone loss (−1.3%/year). Women homozygous for the B allele had 14% lower fractional45Ca absorption compared with women homozygous for the b allele, although this difference was not statistically significant (p = 0.08). We conclude that VDR gene polymorphisms are not associated with BMD or indices of bone turnover in this population of older African-American women. However, DNA sequence variation in the VDR gene or a nearby locus may influence intestinal calcium transport and the rate of postmenopausal bone loss in African-American women.
Universal Standardization of Bone Density Measurements: A Method with Optimal Properties for Calibration Among Several Instruments
Authors: Hui Siu L. , Gao Sujuan , Zhou Xiao-Hua , Johnston C. Conrad , Lu Ying , Glüer Claus C. , Grampp Stephen , Genant Harry 
Published: April 2006

Abstract
The International Dual-Photon X-Ray Absorptiometry (DXA) Standardization Committee (IDSC) conducted a cross-calibration study among three models of DXA machines from three different manufacturers. In that study, 100 subjects were scanned on all three machines. A set of equations were derived to convert bone mineral density (BMD) on each machine to a “standardized BMD” (sBMD) such that sBMD from the same subject derived from different machines would be approximately the same. In a reanalysis of the cross-calibration data, we showed that the conversion method used in the IDSC study did not achieve several optimal properties desirable in such conversions. We derived new conversion equations to sBMD based on minimizing differences among sBMD from the three machines. More important is that the new conversions have no residual bias that was present in the IDSC conversions. The performance of the methods were compared on the cross-calibration data as well as an external data set. We conclude that the IDSC conversions are adequate for clinical use on other machines worldwide, but that researchers should standardize their own machines in a laboratory using the new method.
Methionine-Enkephalin in Bone and Joint Tissues
Authors: Elhassan Adlan M. , Lindgren J. U. , Hultenby K. , Bergstrom J. , Adem Abdu 
Published: April 2006

Abstract
Methionine-enkephalin (met-enk), an endogenous opiate, mimics many of the effects of morphine by binding to opiate receptors, thereby eliciting similar cellular and behavioral effects. Using biochemical and immunohistochemical techniques, several peptides have been identified in bone and joint tissues. Here we report, for the first time, the presence as well as concentration of met-enk in bone and joint tissues. Immunohistochemistry using electron and immunoflourescence microscopy showed cellular and neuronal distribution of met-enk in bone and joint tissues. The concentration of met-enk analyzed by high performance liquid chromatography electrochemical detection or radioimmunoassay was high in bone marrow, periosteum, ankle joint tissue, and cortical bone. Analysis by fast atom bombardment mass spectrometry suggested that the recovered fragment was met-enk. Administration of met-enk inhibits osteoblast cell growth in culture, which is reversible by naltrexone. In arthritic rats, the concentration of met-enk was significantly decreased in ankle joints compared with controls, suggesting a role for met-enk in the pathophysiology of adjuvant arthritis.
Nonsteroidal Anti-Inflammatory Drugs and Bone Mineral Density in Older Women: The Rancho Bernardo Study
Authors: Morton Deborah J. , Dr. Barrett-Connor Elizabeth L. , Schneider Diane L. 
Published: April 2006

Abstract
Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit synthesis of prostaglandins and may help prevent bone loss, but no study has shown the differential association of type or dose of NSAID compound with bone mineral density (BMD). The purpose of this study was to determine the relation of NSAIDs by type and dose to BMD. Participants were 932 Caucasian, community-dwelling women aged 44–98 years from southern California. Data were collected from 1988 to 1991 through the use of standardized medical questionnaires. Medication use was validated by a nurse. BMD at the ultradistal and midshaft radii were measured using single-photon absorptiometry, and at the hip and lumbar spine using dual-energy X-ray absorptiometry. Women (mean age, 72 years) were classified into 818 nonusers and 114 regular daily users of NSAIDs, of which 84 used propionic acid NSAIDs and the remainder used acetic acid NSAIDs. Occasional NSAID users were excluded. Women who used propionic acid NSAIDs, but not acetic acid NSAIDs, had higher BMD at all five sites and significantly higher BMD at the midshaft radius and lumbar spine. These differences remained after controlling for known covariates of osteoporosis. When women with self-reported osteoarthritis were excluded from the model, significantly higher BMD in propionic acid NSAID users was also observed at the femoral neck and total hip. Those who concurrently used estrogen and propionic acid NSAIDs had the highest BMD at all sites, suggesting an additive effect. We conclude that regular daily use of propionic acid NSAIDs, with or without simultaneous use of estrogen, may be helpful in preventing bone loss in older women. However, further research is needed to confirm these results before any clinical practice guidelines can be recommended due to the increased risk of serious complications associated with NSAID use.
Femoral Neck Length and Hip Fracture Risk
Authors: Michelotti John , Clark John 
Published: April 2006

Abstract
To determine whether there are differences in femoral skeletal geometry in fracture-prone subjects when size, positioning diagnosis, and age are controlled, we compared femoral measurements made from the uninvolved hip on 119 plane anteroposterior pelvis radiographs of women without fracture to those of the contralateral hip in a group of 43 female patients with hip fractures (neck, 23; intertrochanteric, 20). The hip was imaged in a standardized position of rotation and adduction. Race, age, and musculoskeletal diagnosis were known. Subjects were grouped by diagnosis of the opposite hip condition (rheumatoid arthritis, osteoarthritis, and normal) and compared. Measurements were also analyzed as ratios to head diameter (HD), neck diameter (ND), and pelvic width. Femoral neck length (NL) was measured from skeletal preparations and imaged in controlled positions of abduction and external rotation. No differences were found between the neck and intertrochanteric fracture groups. The differences between the fracture group and the controls were a thinner femoral cortex (measured at a point one head radius below the lesser trochanter) a larger femoral head, and a larger femoral ND in the fracture group (p &lt; 0.025). The difference in cortical thickness was still significant when scaled by size, but the ratio of HD to ND was equivalent in fractures and controls. No difference in femoral NL could be demonstrated. The experimental measurements showed that apparent NL is significantly position sensitive and this may explain previously reported differences in fracture-prone groups.
Extracellular Ca2+ Increases Cytosolic Free Ca2+ in Freshly Isolated Rat Odontoblasts
Authors: Guo Liang , Dr. Davidson Robert M. 
Published: April 2006

Abstract
Recent evidence suggests that extracellular Ca2+ may modulate cell function in mineralized tissue. To determine whether dentinogenic cells, in particular, are sensitive to extracellular Ca2+, fura-2 microfluorometry was used to monitor intracellular calcium levels in odontoblasts freshly isolated from rat incisor. In response to applications of 0.5–4.0 mM extracellular calcium (CaCl2), most odontoblasts (84%; 107/128) showed an increase in intracellular calcium. For the majority of these cells (70%; 75/107), the typical response was biphasic; there was an initial, transient increase in intracellular calcium which reached peak levels within 30–50 s and decayed rapidly, followed by a slower (&gt; 300 s) recovery toward basal levels. In general, the response of these cells to calcium was repeatable and the mean calcium concentration for the half-maximal response was ∼1.3 mM. This effect could be partially blocked by either 200 μM lanthanum, a nonspecific blocker of Ca2+ channels, or 20 μM dantrolene, a potent inhibitor of Ca2+ release from internal stores. Used in combination, lanthanum, and dantrolene nearly abolished the calcium response completely. In addition, this response was sensitive to the dihydropyridine-sensitive calcium channel blocking agent nicardipine (60 μM), indicating a role for voltage-gated calcium channels during these events. These results show that odontoblasts respond to external calcium through mechanisms involving both influx of external calcium as well as release of calcium from internal stores and suggest a role for extracellular calcium in regulating the function of these cells.
Tartrate-Resistant Acid Phosphatase 5b: A Novel Serum Marker of Bone Resorption
Authors: Halleen Jussi M. , Alatalo Sari L. , Suominen Harri , Cheng Sulin , Janckila Anthony J. , Väänänen H. Kalervo 
Published: April 2006

Abstract
Human serum contains two forms of tartrate-resistant acid phosphatase (TRAP), 5a and 5b. Of these, 5a contains sialic acid and 5b does not. We show here that antigenic properties and pH optimum of TRAP purified from human osteoclasts are identical to those of serum TRAP 5b and completely different from those of serum TRAP 5a, suggesting that 5b would be derived from osteoclasts and 5a from some other source. We developed a novel immunoassay specific for 5b using a monoclonal antibody O1A as capture antibody. O1A did not bind acid phosphatase derived from platelets and erythrocytes. Western analysis showed that O1A was specific for TRAP in both human bone and serum. We measured bound TRAP activity at pH 6.1, where 5b is highly active and 5a almost completely inactive. The immunoassay detected more than 90% of the initial TRAP 5b activity after 8-h incubation of serum samples at 25°C and after 3 days incubation at 4°C. Serum TRAP 5b activity decreased significantly after 6 months of hormone replacement therapy (HRT) of postmenopausal women compared with the change observed in postmenopausal women receiving placebo (p &lt; 0.0001). Instead, no significant differences were observed between the changes in the placebo and HRT groups in total serum TRAP amount. These results show that serum TRAP 5b is a specific and sensitive marker for monitoring antiresorptive treatment. Instead, total serum TRAP cannot be used for that purpose. These findings may turn out to be a significant improvement in using serum TRAP as a resorption marker.
Association of a Polymorphism in the TNFR2 Gene with Low Bone Mineral Density
Authors: Spotila L. D. , Rodriguez H. , Koch M. , Adams K. , Caminis J. , Tenenhouse H. S. , Tenenhouse A. 
Published: April 2006

Abstract
Previous genetic linkage data suggested that a gene on chromosome 1p36.2–36.3 might be linked to low bone mineral density (BMD). Here, we examine the gene for tumor necrosis factor receptor 2 (TNFR2), a candidate gene within that interval, for association with low BMD in a group of 159 unrelated individuals. We assess two polymorphic sites within the gene, a microsatellite repeat within intron 4, and a three-nucleotide variation in the 3′ untranslated region (UTR) of the gene. The latter has five alleles of which the rarest allele is associated with low spinal BMD Z score (p = 0.008). Lowest mean spinal BMD Z scores were observed for individuals having genotypes that were heterozygous for the rarest allele. No homozygotes for the rarest allele were observed. Preliminary analysis suggests that there is a difference in the genotype frequency distribution between the group with low BMD and a control group.
Effect of Long-Term Exposure to Fluoride in Drinking Water on Risks of Bone Fractures
Authors: Li Yiming , Liang Chaoke , Slemenda Charles W. , Ji Rongdi , Sun Shuzhuang , Cao Jingxiang , Emsley Christine L. , Ma Feng , Wu Yunpeng , Ying Po , Zhang Yan , Gao Sujuan , Zhang Wu , Katz Barry P. , Niu Shiru , Cao Shouren , Johnston Conrad C. 
Published: April 2006

Abstract
Findings on the risk of bone fractures associated with long-term fluoride exposure from drinking water have been contradictory. The purpose of this study was to determine the prevalence of bone fracture, including hip fracture, in six Chinese populations with water fluoride concentrations ranging from 0.25 to 7.97 parts per million (ppm). A total of 8266 male and female subjects ≥50 years of age were enrolled. Parameters evaluated included fluoride exposure, prevalence of bone fractures, demographics, medical history, physical activity, cigarette smoking, and alcohol consumption. The results confirmed that drinking water was the only major source of fluoride exposure in the study populations. A U-shaped pattern was detected for the relationship between the prevalence of bone fracture and water fluoride level. The prevalence of overall bone fracture was lowest in the population of 1.00-1.06 ppm fluoride in drinking water, which was significantly lower (p &lt; 0.05) than that of the groups exposed to water fluoride levels ≥4.32 and ≤0.34 ppm. The prevalence of hip fractures was highest in the group with the highest water fluoride (4.32-7.97 ppm). The value is significantly higher than the population with 1.00-1.06 ppm water fluoride, which had the lowest prevalence rate. It is concluded that long-term fluoride exposure from drinking water containing ≥4.32 ppm increases the risk of overall fractures as well as hip fractures. Water fluoride levels at 1.00-1.06 ppm decrease the risk of overall fractures relative to negligible fluoride in water; however, there does not appear to be similar protective benefits for the risk of hip fractures.
Microarray Analysis of Bone Morphogenetic Protein, Transforming Growth Factor β, and Activin Early Response Genes During Osteoblastic Cell Differentiation
Authors: De Jong Diana S. , Van Zoelen Everardus J. J. , Bauerschmidt Susanne , Olijve Wiebe , Steegenga Wilma T. 
Published: April 2006

Abstract
Bone morphogenetic protein (BMP) 2, a member of the transforming growth factor (TGF) β family, is a potent regulator of osteoblast differentiation. In addition, both TGF-β and activin A can either induce bone formation or inhibit bone formation depending on cell type and differentiation status. Although much is known about the receptors and intracellular second messengers involved in the action of TGF-β family members, little is known about how selectivity in the biological response of individual family members is controlled. In this study, we have investigated selective gene induction by BMP-2, TGF-β1 and activin A in relation to their ability to control differentiation of mouse mesenchymal precursor cells C2C12 into osteoblastic cells. TGF-β1 can inhibit BMP-2-induced differentiation of these cells, whereas activin A was found to be without morphogenetic effect. Using a gene expression microarray approach covering 8636 sequences, we have identified a total of 57 established genes and expressed sequence tags (ESTs) that were either up-regulated or down-regulated 2 h after treatment with at least one of these three stimuli. With respect to the established genes, 15 new target genes for TGF-β family members thus were identified. Furthermore, a set of transcripts was identified, which was oppositely regulated by TGF-β1 and BMP-2. Based on the inverse biological effects of TGF-β1 and BMP-2 on C2C12 cells, these genes are important candidates for controlling the process of growth factor-induced osteoblast differentiation.
Reversal of Secondary Hyperparathyroidism by Phosphate Restriction Restores Parathyroid Calcium-Sensing Receptor Expression and Function
Authors: Ritter Cynthia S. , Martin Daniel R. , Lu Yan , Slatopolsky Eduardo , Brown Alex J. 
Published: April 2006

Abstract
Secondary hyperparathyroidism (2° HPT), a common disorder in chronic renal failure (CRF) patients, is characterized by hypersecretion of parathyroid hormone (PTH), parathyroid hyperplasia, and decreased expression of the calcium-sensing receptor (CaR). Dietary phosphate loading promotes 2° HPT, and phosphate restriction prevents and arrests 2° HPT in CRF. This study examined the ability of phosphate restriction to restore parathyroid CaR expression and function. Uremic rats fed a 1.2% P diet for 2 weeks developed 2° HPT with down-regulated CaR expression. Continuation on the 1.2% P diet for 2 more weeks worsened the 2° HPT and further decreased CaR, but switching the rats to a 0.2% P diet for 2 weeks normalized PTH, arrested parathyroid hyperplasia, and restored CaR expression to normal. The calcium-PTH relationship was abnormal in uremic rats fed a high phosphate (HP) diet with a right-shifted calcium set point but was corrected by 2 weeks of phosphate restriction. A time course revealed that following the switch to a low phosphate diet, PTH levels were normalized by day 1, and growth was arrested by day 2, but CaR expression was restored between days 7 and 14. We conclude that although phosphate restriction restores CaR expression and function in parathyroid glands of uremic rats, it is a late event and not involved in the arrest of 2° HPT.