bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteosarcoma hybrids can preferentially target alkaline phosphatase activity to matrix vesicles: Evidence for independent membrane biogenesis
Authors: Leach R.J. , Schwartz Z. , Johnson-Pais T.L. , Dean D.D. , Luna M. , Boyan B.D. 
Published: February 2010

Abstract
Alkaline phosphatase is the marker enzyme for matrix vesicles, extracellular organelles that play a major role in primary bone formation and calcification. Recently, we developed osteosarcoma × fibrosarcoma hybrids in which alkaline phosphatase expression was greatly reduced, a phenomenon known as extinction. In the present study, we used two cell hybrids, LTA-1 and LTA-5, constructed from a human osteoblast-like osteosarcoma, TE85, and a mouse fibrosarcoma, La−t−, to examine the differential distribution of alkaline phosphatase between matrix vesicles and the plasma membrane, postulated to be the parent membrane from which matrix vesicles are derived. While alkaline phosphatase in plasma membranes was extinguished, enzyme activity in matrix vesicles from LTA-1 hybrid cells was 34.2% of that present in matrix vesicles from the TE85 parent cells and 200 times that found in La−t− matrix vesicles. Matrix vesicles from LTA-5 had alkaline phosphatase levels similar to La−t−. When other membrane enzymes (phospholipase A2, 5′-nucleotidase, and Na+/K+ ATPase) were examined, hybrid matrix vesicle and plasma membrane levels were similar to those of TE85 and significantly higher than in La−t− membrane fractions. Northern analysis detected mRNA for alkaline phosphatase in TE85 cells, but not in the hybrids or La−t− cells. In contrast, reverse transcription-polymerase chain reaction (RT-PCR) revealed alkaline phosphatase mRNA in the hybrid cells, but at very low levels. Taken together, the data indicate that regulation of plasma membrane and matrix vesicle alkaline phosphatase is independent and suggest that matrix vesicle biogenesis is independent and distinct from that of plasma membrane biogenesis. Analysis of 1B- and 1L-type alkaline phosphatase mRNA by RT-PCR showed that alternate promoter usage of the alkaline phosphatase gene was not responsible for the differential localization of this enzyme in matrix vesicle. Thus, it is likely that matrix vesicle and plasma membrane alkaline phosphatase are regulated differently at a post-transcriptional level.
Effects of a one-year high-intensity versus low-intensity resistance training program on bone mineral density in older women
Authors: Pruitt Leslie A. , Taaffe Dennis R. , Marcus Robert 
Published: February 2010

Abstract
The purpose of this study was to determine the effects of a 12-month resistance training program, of two different intensities, on bone mineral density (BMD) in healthy, older women. Twenty-six Caucasian women (aged 65–79 years) completed the study. Subjects were randomly assigned to one of three groups: high-intensity (HI; n = 8), low-intensity (LI; n = 7), and control (CON; n = 11). The active groups performed 10 exercises, 3 days/week under supervision. Exercise intensity was maintained at 80% of one-repetition maximum (1-RM) for the HI group, and at 40% 1-RM for the LI group. The volume of work was maintained constant between the two groups by assigning the LI group twice as many repetitions for each exercise. Maximal muscular strength and BMD of the lumbar spine and total hip were measured at baseline and at 12 months. Strength was evaluated using the 1-RM method, and BMD was determined by dual-energy X-ray absorptiometry. Exercise session attendance was similar for the two groups (81.0% HI; 76.8% LI). Muscular strength improved in the exercisers compared with the CON group (p ≤ 0.05). Percentage change in lumbar spine BMD was 0.7 ± 1.9%, 0.5 ± 2.4%, and -0.1 ± 2.3% for the HI, LI, and CON groups, respectively. Percentage change in total hip BMD was 0.8 ± 2.3% (HI), 1.0 ± 1.7% (LI), and 0.9 ± 1.3% (CON). Group differences in BMD change were not significant (p &gt; 0.05). These findings suggest that high-intensity and low-intensity resistance training regimens effectively increase muscular strength, but not lumbar spine or total hip BMD, in healthy, older women.
Choosing between predictors of fractures
Authors: Dr. Hui Siu L. , Slemenda Charles W. , Carey Mark A. , Johnston Conrad C. 
Published: February 2010

AbstractThe identification of those at highest risk of osteoporotic fractures is a clinical goal that requires appropriate statistical comparisons of potential predictors of fractures. This article provides a formal approach for comparing individual predictors (e.g., bone mass at one site vs bone mass at another), or sets of predictors (e.g., bone mass vs other risk factors), and contrasts newer methods, such as bootstrapping, to receiver-operating-characteristics (ROC) curves, which have been previously used. The advantages of the bootstrapping approach are illustrated using time-to-fracture data from a published study demonstrating the use of baseline bone mass measurements in the prediction of fractures in 521 subjects with variable lengths of follow-up, extending to 12.5 years. Bone mineral density (BMD) was shown to be significantly better than bone mineral content (BMC) in predicting fractures in free-living subjects, but not in retirement-community subjects. Bone mineral apparent density (BMAD) was also compared with BMC and BMD and shown not to improve fracture prediction in these subjects.
Effects of recombinant insulin-like growth factor-I and growth hormone on bone turnover in elderly women
Authors: Ghiron Laura J. , Thompson Janice L. , Holloway Leah , Hintz Raymond L. , Butterfield Gail E. , Hoffman Andrew R. , Marcus Robert 
Published: February 2010

Abstract
We evaluated the effects of recombinant insulin-like growth factor-I (IGF-I) and growth hormone (GH) on calciotropic hormones and bone turnover markers in 16 healthy elderly women 71.9 ± 1.3 years of age (mean ± SEM). Subjects consumed a fixed diet providing 1000 mg of calcium and 0.9 g/kg of protein for 10 days before starting baseline 24-h urine and blood collections. Specimens were collected for 6 consecutive days before initiating subcutaneous injections of GH (25 μg/kg/day, n = 5) and IGF-I at 60 μg/kg b.i.d. (high-dose, n = 5) or at 15 μg/kg b.i.d. (low-dose, n = 6) for 28 days. Resorption markers included urine hydroxyproline (OHP), total pyridinolines (PYD), and N-telopeptide; formation markers included osteocalcin, skeletal alkaline phosphatase (sALP), and type I procollagen carboxy-terminal extension peptide (CICP). For each subject, baseline daily turnover markers varied substantially (CV = 16–22%). With GH and high-dose IGF-I, resorption and formation markers increased progressively to maximum levels at day 21. For GH, the increase in day 21 PYD, N-telopeptide, osteocalcin, and CICP was 143, 111, 53, and 81%, respectively (p &lt; 0.06–0.02). For high-dose IGF-I, these increases were 108, 81, 77, and 111% (p &lt; 0.02–0.002). However, with low-dose IGF-I, no change was observed in resorption markers while osteocalcin and CICP increased progressively (day 21, % increases = 88 ± 51, 36 ± 14). Twenty-four hour urine collections during the last days of baseline and of study drug were taken as six 4 h aliquots. When deoxyPYD was measured on these samples in the low-dose IGF-I group, a significant increase was observed only on the 0800–1200 h aliquot. Serum phosphorus concentrations increased with GH (21.2 ± 3.3%) and high-dose IGF-I (8.8 ± 3.6%) by day 21 but actually decreased by day 28 (−9.7 ± 2.7, p &lt; 0.02) with low-dose IGF-I. Urinary phosphorus excretion decreased with high-dose IGF-I only. Twenty-four hour calcium excretion increased with all treatments. These results indicate that both GH and high-dose IGF-I activate remodeling osteons. By contrast, low-dose IGF-I may directly increase osteoblastic function with only a minimal increase in bone resorption and may therefore provide a useful means to increase bone mass. The results also suggest some of the GH action on renal phosphorus handling represents a direct action of GH on the nephron which does not involve the intermediacy of IGF-I. Finally, even under controlled conditions bone turnover markers exhibit substantial daily variation so that a very large treatment effect will be required for these markers to have clinical utility.
The effects of recombinant human insulin-like growth factor (rhIGF)-1 and rhIGF-1/IGF binding protein-3 administration on rat osteopenia induced by ovariectomy with concomitant bilateral sciatic neurectomy
Authors: Narusawa Ken'Ichiro , Nakamura Toshitaka , Suzuki Katsumi , Matsuoka Yasushi , Lee Lyang-Ja , Tanaka Hiroyuki , Seino Yoshiki 
Published: February 2010

Abstract
We compared the effect of administration of recombinant human insulin-like growth factor-1 (rhIGF-1) alone or the rhIGF-1/IGF binding protein-3 (IGFBP-3) complex on osteopenia in rats. Female Sprague-Dawley rats (8 months old) underwent combined ovariectomy and bilateral sciatic neurectomy (OVX-NX) or sham operation only. After 2 months, the OVX-NX animals were injected subcutaneously with rhIGF-1 alone or with rhIGF-1/IGFBP-3 equimolar complex for 4 weeks. The IGF-1 contents and dose were 0.3 mg/kg of body weight (BW) three times/week, 3 mg/kg of BW once/week, or 3 mg/kg of BW three times/week. At the end of the experiment, the 4th and 5th lumbar vertebrae (L4, L5) and the proximal tibiae were removed after tetracycline labeling, and histomorphometrical analyses were performed on undecalcified sections using Villanueva's staining. The cancellous bone volume at L5 significantly increased by thickening of the trabecular width in rats treated with the complex. However, the increase in the values at the proximal tibia was not significant. The bone formation rates (BFR/BS) in the lumbar vertebrae of rats treated with the complex three times a week at doses of 0.3 mg/kg of BW and 3 mg/kg of BW were both significantly increased but the parameter increase was less marked with the dose of 3 mg/kg of BW once/week. The BFR/BS did not increase significantly in animals treated with IGF-1 alone. These findings clearly demonstrated that the effect of systemically administered rhIGF-1 on bone formation was markedly potentiated when combined with IGFBP-3 in estrogen deficiency combined with reduced activity. The action of IGF-1 was less potent on the bone in paralyzed limbs. The action of rhIGF-1/IGFBP-3 on trabecular bone appeared to depend not only on the dose but also on the frequency of administration and the parts of the skeleton in rats.
Parathyroid hormone-related protein is an autocrine modulator of rabbit proximal tubule cell growth
Authors: García-Ocaña Adolfo , de Miguel Fernando , Peñaranda Carlos , Albar Juan P. , Sarasa Jose L. , Esbrit Pedro 
Published: February 2010

Abstract
Parathyroid hormone-related protein (PTHrP), a likely mediator for humoral hypercalcemia of malignancy, is also synthesized in various normal tissues. In the kidney, PTHrP, mainly detected in proximal and distal tubules, has been shown to stimulate proliferation of rat mesangial cells in culture. Experiments were carried out to investigate the possible mitogenic effect of PTHrP in cultures of rabbit proximal tubule cells (PTC). Immunocytochemical analysis, using antihuman (h)PTHrP antibodies to (38–64) and (107–111) epitopes in the PTHrP molecule, showed strong cytoplasmic staining in PTC and in proximal tubule-like LLC-PK1 cells. PTC secreted immunoreactive PTHrP (54.8 ± 7.0 fmol/106 cells) into the culture medium. Human PTHrP(1–141) stimulated proliferation in subconfluent cultures of these cells dose-dependently. This effect was similar to that induced by [Tyr34]hPTHrP(1–34) amide (hPTHrP[1–34]), hPTHrP(1–86), and bovine (b)PTH(1–34), while hPTHrP(38–64) amide, hPTHrP(107–111) amide, and hPTHrP(107–139) amide were ineffective. Addition of anti-hPTHrP neutralizing antibodies to (1–34), (38–64), and (107–111) epitopes of PTHrP decreased PTC growth. The mitogenic effect of these agonists was abolished in confluent PTC. In contrast, [Nle8,18, Tyr34]bPTH(3–34) amide (bPTH[3–34]) increased DNA synthesis in either subconfluent or confluent PTC. In LLC-PK1 cells, which also secreted PTHrP and are devoid of PTH receptors, none of these peptides affected proliferation. Forskolin (10 μM) or H-8 (2 μM), a protein kinase A inhibitor, did not affect basal or hPTHrP(1–34)-stimulated DNA synthesis, respectively, in subconfluent PTC. On the other hand, 10 nM staurosporine and 100 nM calphostin C, protein kinase C (PKC) inhibitors, blunted the effects of hPTHrP(1–34) or bPTH(3–34) on DNA synthesis in these cells. These studies suggest that PTHrP may function as an autocrine factor in the regulation of proximal tubule cell growth by a PKC-mediated mechanism.
Circadian variation in urinary excretion of bone collagen cross-links
Authors: Bollen Anne-Marie , Martin Michael D. , Leroux Brian G. , Eyre David R. 
Published: February 2010

Abstract
Bone resorption can be evaluated by measuring the urinary excretion of collagen type I cross-linked N telopeptides (NTx). Since it is difficult to obtain (and verify) 24 h urine collections from patients, untimed spot urines are more practical. Such measurements, however, need correction for urine dilution and potentially may vary with collection time since a circadian rhythm in bone metabolism has been reported. This study examined cross-link excretion in urine voids serially collected during a 24 h period from subjects living their normal daily routine (as opposed to a controlled hospital setting). This mimics the situation for walk-in patients visiting a clinician and providing a spot urine. A total of 35 dentists (20 males, 15 females) collected all urine voids separately over a 24 h period. Urines were analyzed for creatinine and NTx. The effects of time of day on the excretion rates of these metabolites (in nmol/h) and on the cross-link:creatinine ratio were assessed. A circadian rhythm was evident in the excretion rate of creatinine with a peak in the late afternoon (18% higher than the 24 h mean, p = 0.0004). The NTx excretion rate peaked in the morning (9% higher than the 24 h mean) but this latter rhythm was not statistically significant (p = 0.31). The NTx:creatinine ratio fell during the day from a high (122% of the 24 h mean) in the early morning to a low in the early evening. This rhythm in the NTx:creatinine ratio in untimed spot urines was statistically significant (p &lt; 0.0001). In conclusion, the NTx:creatinine ratio in spot urines from adult outpatient subjects showed a significant circadian rhythm. Variations in creatinine excretion were the primary cause. Time of day should, therefore, be taken into account when comparing test results of spot urines with normal ranges or with other samples from the same subject.
Regulation of gap junction intercellular Communication by pH in MC3T3-E1 osteoblastic cells
Authors: Yamaguchi Dean T. , Huang Jason T. , Ma Defang 
Published: February 2010

AbstractGap junction intercellular communication (GJIC) may be related to coordinating the function of osteoblasts during bone mineralization. Since an alkaline pH supports mineral deposition while an acidic pH promotes mineral dissolution, it was investigated whether GJIC is altered by changes in extracellular pH (pHo) Functional GJIC was assessed by fluorescent dye transfer after microinjection, and connexin protein abundance was examined by immunoprecipitation and immunoblotting in MC3T3-E1 cells, a model of osteoblast-like cells. The percent of cells coupled by GJIC was found to be 40.7% (24 of 59 injected cells) at pH 6.9, 72.2% (26 of 36) at pH 7.2, and 92.8% (26 of 28) at pH 7.6. A decrease in GJIC was detectable by 30–60 minutes of exposure to a pHo of 6.9. Decreased gap junction communication was also found in cells after 3, 8, and 24 h of incubation in a bicarbonate-CO2 system at an ambient pH of 6.9. Connexin protein abundance experiments showed that at after exposure to a pH of 6.9 for 2.75 h, the specific band(s) at 41–43 kD were fainter compared with these same band(s) at pH 7.2 and 7.6. There was no significant difference in band densities at pH 7.2 and 7.6. Determination of intracellular pH (pHi) showed that it was similar to pHo after 2.75 h of incubation at each ambient pH. When pHi was clamped at 6.9 or 7.2, there was a time-dependent decrease in the gap junction coupling frequency at a pHi of 6.9 when pHo was 7.2. Steady-state mRNA levels were decreased at pHo 6.9 but were unchanged at either pHo 7.2 or 7.6. Our conclusions are that (1) longer incubations (≥2.75 h) at low pHo decrease GJIC which in part may be due to a decrease in connexin protein abundance perhaps as a result of a decrease in connexin steady-state mRNA expression; (2) GJIC inhibition or augmentation found at low and high pHo, respectively, suggests that gating of the GJ channel by pH may also occur; (3) pHo-induced alterations in GJIC in the MC3T3-E1 osteoblastic model are related to concomitant changes in pHi.
Predictors of hip fractures in elderly men
Authors: Poór Gyula , Atkinson Elizabeth J. , O'Fallon W. Michael , Melton L. Joseph 
Published: February 2010

Abstract
To assess the influence on the risk of hip fractures in men of medical conditions associated with secondary osteoporosis or with an increased likelihood of falling, we conducted a population-based nested case-control study among the 232 Rochester, Minnesota, men with an initial hip fracture due to moderate trauma in 1965–1989 and an equal number of age-matched control men from the general population. Information on selected medical and surgical conditions and certain behavioral risk factors prior to fracture (or comparable index date for controls) was obtained from inpatient and outpatient medical records in the community that averaged over 36 years in duration. After adjusting for age, obesity, and inactivity, disorders linked with secondary osteoporosis were associated with a 2-fold increase in the risk of hip fracture in men (odds ratio [OR] 2.3; 95% confidence interval [CI] 1.3–4.3), while conditions linked with an increased risk of falling were associated with almost a 7-fold increase in risk (OR 6.9; 95% CI 3.3–14.8). These factors together appeared to account for about 72% of the hip fractures in men. Increased attention must be paid to these conditions which, in aggregate, are very common in elderly men and lead to a substantial increase in the risk of hip fracture with its devastating sequelae of death, disability, and cost.
Measurement of femoral geometry in type I and type II osteoporosis: Differences in hip axis length consistent with heterogeneity in the pathogenesis of osteoporotic fractures
Authors: Boonen Steven , Koutri Rosetta , Dequeker Jan , Aerssens Jeroen , Lowet Geert , Nijs Jos , Verbeke Geert , Lesaffre Emmanuel , Geusens Piet 
Published: February 2010

Abstract
The epidemiologic patterns of vertebral and femoral fractures are sufficiently different to suggest that they represent distinct disorders (type I versus type II osteoporosis) although osteopenia is common in both. To determine whether differences in femoral geometry, one of the main determinants of bone quality, might contribute to the heterogeneity in osteoporotic fractures, we obtained dual energy X-ray absorptiometry scans on 210 women age 60 or older, including 105 type 1 fracture cases, 30 type II patients, and 75 controls. Hip axis length, measured on the scan printout, was significantly increased (p &lt; 0.01) in hip fracture patients compared with women with postmenopausal osteoporosis, whereas femoral neck density (BMD) was equal in both groups. The best discrimination between both fracture types was obtained by a logistic regression model based on age and axis length. Adding BMD to the model did not improve the discriminative power (p = 0.67). These data provide further evidence that geometric characteristics may be implicated in hip fracture risk. Furthermore, these findings suggest that an increase in hip axis length may predispose osteopenic subjects to a femoral localization of fragility fractures, consistent with the postulated heterogeneity in the pathogenesis of osteoporotic fractures.
Equivalent deficits in bone mass of the vertebral body and posterior processes in women with vertebral fractures: Implications regarding the pathogenesis of spinal osteoporosis
Authors: Prof. Seeman Ego , Formica Carmelo , Mosekilde Lis 
Published: February 2010

Abstract
Reduced bone mass of the spine in women with vertebral fractures is attributed to excessive trabecular bone loss from the vertebral body. However, the measurement obtained by posteroanterior (PA) scanning includes the posterior processes and the vertebral body, each comprising about 50% of the total vertebral mass. Thus, the deficit in bone mass by PA scanning may be due to deficits in one or both of these structures. We asked two questions: (1) In healthy women, is the age-related diminution in bone mass of the vertebral body greater than the diminution at the posterior processes? (2) In women with vertebral fractures, is the deficit in bone mass at the vertebral body, the fracture site in spinal osteoporosis, greater than at the posterior processes? Bone mass of the posterior processes and vertebral body of the third lumbar vertebra was measured by lateral scanning using dual-energy X-ray absorptiometry (DXA). Compared with 27 premenopausal women, deficits in 27 postmenopausal women at the posterior processes and vertebral body, respectively, were 35.9 ± 3.7 and 25.2 ± 4.1% (p &lt; 0.05); t score, –1.5 ± 0.2 and –1.1 ± 0.2 SD (p = 0.09). Compared with the postmenopausal (age-matched) women, deficits in 21 women with vertebral fractures at the posterior processes and vertebral body, respectively, were 22.6 ± 4.9 and 24.5 ± 8.3% (p = NS); Z score, –0.8 ± 0.2 and –0.8 ± 0.3 (p = NS). In vivo the bone mass of the vertebral body as a percentage of the whole vertebra was 45.7 ± 0.1 in premenopausal women, 48.9 ± 1.9 in postmenopausal women, 51.5 ± 1.1 in women with low bone mass but no fractures, 52.7 ± 2.4 in women with vertebral fractures, and 51.9 ± 2.5% in vitro, based on autopsy specimens from 19 postmenopausal women aged 65–95 years. The lower spinal bone density measured using PA scanning in women with spine fractures may not be due to excessive or disproportionate trabecular bone loss from the vertebral body because comparable deficits are found at the posterior processes. Whether these deficits are due to reduced peak bone mass, trabecular bone loss, cortical bone loss, or varying combinations of these mechanisms remains to be established.
Segregation analysis and variance components analysis of bone mineral density in healthy families
Authors: Guéguen René , Jouanny Pierre , Guillemin Francis , Kuntz Claude , Pourel Jacques , Siest Gérard 
Published: February 2010

Abstract
Bone mineral density (BMD) was measured in 1992–93 in 129 nuclear families, including 258 parents and 183 children, and was analyzed for familial resemblance factors. BMD measurements were adjusted on weight and age. Segregation analysis rejected the monogenic hypothesis and exhibited a strong polygenic component. Variance components analysis was then used to estimate the parameters of a multivariate normal model including an additive polygenic component, a common environmental factor, and a residual specific to each individual. The genetic component was independent of sex and age. The common environmental factor was not significant. The variance of the residual specific factor appeared to be a quadratic function of age, reaching its minimum value at 26.4 years. Consequently, the maximum value for heritability (ratio of genetic variance to total variance) is observed at this age (h2 = 0.84). According to this model, the correlation between two relatives is a function of the ages of each individual in the pair.