bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lower serum osteocalcin in ethanol-fed rats
Authors: Peng Tai-Chan , Lian Jane B. , Hirsch Philip F. , Kusy Robert P. 
Published: February 2010

AbstractSerum osteocalcin was remarkably and significantly (-34 and −41% in two separate experiments; p &lt; 0.001) lower in rats fed an 8% (w/v) ethanol liquid diet (ELD) for 1 week than in rats fed an isocaloric control liquid diet (CLD). In a longer experiment that spanned 4 weeks, the ELD rats were given 6% ethanol on day 4, increased stepwise to 8% by day 9, and then maintained at 8% until day 28, when the experiment was terminated. Again, serum osteocalcin was much lower (-32%, p &lt; 0.001) in the ELD-fed rats than in CLD-fed rats. Even in rats fed only a 6% ELD for 12 days, serum osteocalcin was lower (-33%, p &lt; 0.001) than in controls. Also, the femora were weaker, more compliant, and more ductile in ELD- than in CLD-fed rats, findings that confirmed our earlier, related work. The fall in serum osteocalcin in ELD-fed rats is associated with a fall in femur ash weight and bone strength. There were significant correlations between serum osteocalcin and bone strength (r = 0.80; p &lt; 0.001) and between serum osteocalcin and bone stiffness (r = 0.83; p &lt; 0.001). Serum ionized calcium, like osteocalcin, was consistently lower in rats given ethanol for 1 or 4 weeks than in controls. From these experiments we conclude that excessive ethanol consumption inhibits osteoblastic activity as indicated by the reduced serum osteocalcin. The inhibition is also associated with other deleterious effects of ethanol on bone, including ash weight, bone strength, and bone stiffness. These results in rats suggest that serum osteocalcin may be a useful biologic marker of bone status in alcoholic patients.
Human osteoblastlike cells do not respond to interleukin-6
Authors: Littlewood A.J. , Aarden L.A. , Evans D.B. , Russell R.G.G. , Gowen M. 
Published: February 2010

Abstract
Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. It has been implicated in the control of connective tissue cells in such conditions as rheumatoid arthritis and osteoporosis. We have investigated the effects of recombinant human interleukin-6 (rhIL-6) on human osteoblastlike cells derived from explants of trabecular bone. ROS 17/2.8 cells were used as an additional osteoblastlike cell model system.
We were unable to identify any effects of rhIL-6 (5–5000 pg/ml) on the proliferation, alkaline phosphatase activity, osteocalcin production, or release of cytokines or prostaglandins by either osteoblastlike cell model system. Since we have shown previously that these cells release IL-6 in culture, we used a sheep anti-human IL-6 antibody to investigate the possibility that (1) action of added exogenous IL-6 could be masking endogenous production, and (2) endogenous IL-6 may regulate the effects of osteotropic agents on the osteoblastlike cells. Presence of the antibody exerted no detectable effects on 1,25-(OH)2D3-stimulated alkaline phosphatase or on proliferation or TNF production enhanced by IL-1. Thus IL-6 does not appear to be involved in the regulation of osteoblast activity.
Chicken parathyroid hormone-related protein and its expression during embryologic development
Authors: Schermer D.T. , Chan S.D.H. , Bruce R. , Nissenson R.A. , Wood W.I. , Dr. Strewler G.J. 
Published: February 2010

Abstract
A parathyroid hormone-related protein (PTHrP) is the probable cause of humoral hypercalcemia in malignancy, but its normal physiologic role remains unknown. Since current evidence suggests that PTHrP may have a role in embryonic development, we cloned a genomic fragment that encodes chicken PTHrP (cPTHrP) and studied the expression of PTHrP in developing chick embryos. Blot hybridization of chicken genomic DNA with a cPTHrP genomic DNA probe showed a single band, suggesting that a single-copy gene encodes cPTHrP. By screening a chicken genomic library with the human probe an open reading frame was identified that corresponds to the human PTHrP (hPTHrP) exon IV. Compared to the human sequence the 5′ splice junction is highly conserved and the two predicted propeptide residues are identical. The sequence predicts a mature peptide of 139 amino acids; all of the first 21 and 94 of the first 112, but only 8 of the final 27 residues of cPTHrP are identical to the human sequence. The structural features required for PTH receptor binding and activation are highly conserved between chicken and hPTHrP. Poly(A)-enriched RNA from 3–15 day chicken embryos was surveyed by hybridization to the chicken probe. A hybridizing band of 1.45 kb was found in tissues derived from all three germ layers, including brain, heart, lung, liver, gizzard, intestine, chorioallantoic membrane, yolk sac, and skeletal muscle. An additional 1.2 kb hybridizing band was found in some tissues. The conservation of the PTHrP sequence between chicken and mammals supports the view that PTHrP has an important physiologic role. The presence of PTHrP mRNA in early embryos suggests that this role may be in embryonic development.
Intertissular variations in osteonectin: A monoclonal antibody directed to bone osteonectin shows reduced affinity for platelet osteonectin
Authors: Malaval Luc , Darbouret Bruno , Preaudat Corinne , Jolu Jean-Pierre , Dr. Delmas Pierre D. 
Published: February 2010

Abstract
Osteonectin, a major noncollagenous protein of bone, is also synthesized and secreted by various nonmineralized tissues and by platelets. To establish whether there are structural specificities of osteonectin according to its tissular origin, we raised 12 monoclonal antibodies against bovine bone osteonectin and screened them for their ability to recognize bone and platelet osteonectin. When hybridoma culture media were radio-immunoassayed all MAbs showed the same titer for [125I]human platelet osteonectin and for [125I]bovine bone osteonectin, except MAb 2, which poorly bound platelet osteonectin. Immunoprecipitation and immunoblotting experiments were performed on human bone protein extracts and on material secreted by human platelets upon thrombin stimulation; in these experiments MAb 2 recognized human bone osteonectin and only faintly human platelet osteonectin. A “sandwich” immunoradiometric assay was devised in which osteonectin bound to a solid phase by a first MAb was recognized by a 125I-labeled second MAb. In this assay MAb 2, used as a tracer, showed a 100-fold lower affinity for purified human platelet osteonectin than for purified human bone osteonectin. These results suggest the existence of structural variations in osteonectin obtained from bone and platelets. Whether these variations result from differences in sequence, post-translational processing, or postsecretional fate remains to be established.
The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats
Authors: Seedor J. Gregory , Quartuccio Helen A. , Thompson David D. 
Published: February 2010

AbstractEstrogen deficiency in mammals is known to increase bone turnover and result in reduced bone mass. The bisphosphonate, 4-amino-1-hydroxybutylidene-1,1-bisphophonic acid disodium salt, alendronate (MK-217), is a potent inhibitor of bone resorption and was evaluated in this study for its ability to inhibit bone loss following ovariectomy in rats. Alendronate was administered sc in doses of 0.0, 0.056, 0.28, 1.40, and 7.0 mg P/kg/month, divided into two, four, or eight monthly subcutaneous injections for each dose, to female Sprague-Dawley rats (250-280 g) that underwent bilateral ovariectomy. Rats were sacrificed 12 weeks postovariectomy, the femora ashed, and the tibiae prepared for static and dynamic histomorphometric analyses.Femoral bone mass in vehicle-treated rats was reduced by 12% 12 weeks after ovariectomy compared to the nonovariectomized control group. In MK-217-treated rats femoral bone mass was significantly increased in a dose-dependent manner compared to either ovariectomized or nonovariectomized controls. Histomorphometric analysis showed significant increases in tibial trabecular bone volume with no decrease in osteoclast number. Doses delivered twice per month or eight times per month were equally effective in achieving the peak bone volume 12 weeks after ovariectomy.In conclusion, alendronate (MK-217) was effective in inhibiting bone loss due to estrogen deficiency in rats, and the magnitude of its effect was related primarily to the total amount of compound administered rather than the frequency of its administration.
High-conductance anion channels in embryonic chick osteogenic cells
Authors: Ravesloot Jan H. , van Houten Ron J. , Ypey Dirk L. , Nijweide Peter J. 
Published: February 2010

Abstract
Patch-clamp measurements done on excised membrane patches obtained from 1-5 day cultured embryonic chick osteoblasts, osteocytes, and periosteal fibroblasts revealed the existence of a high-conductance anion channel: 371 ± 63 pS when measured under symmetrical 158 mM CI− conditions. The channel frequently displayed subconductance levels. The ion selectivity of the channel expressed as the (an)ion to chloride permeability ratio was as follows: CI− (1.0) &gt; methylsulfate− (0.71) &gt; gluconate− (0.25) &gt; glutamate− (0.17) &gt; Na+ = K+ (0.10). In addition, the channel had a significant permeability for inorganic phosphate ions. The channel was found in about 1% of the cell-attached patches, which indicates that the channel is under the control of as yet unknown intracellular factors. Once activated by patch excision, the channel was voltage dependent and active at potentials close to 0 mV. At potentials outside the range of ± 10 mV channel activity decreased. This process proceeded faster at increasing membrane potentials of either polarity. Returning to potentials close to 0 mV caused reopening of the channels within seconds if the preceding voltage step led to complete closure of the channels. Channel activity did not depend noticeably on intracellular and extracellular Ca2+ ions. The channel is not unique to (chick) osteogenic cells but has been demonstrated in excised patches obtained from excitable and other nonexcitable cells. Although its presence in a wide variety of cell types suggests that the channel plays a general role in as yet unknown cell physiologic processes, the channel may also have specific functions in osteogenic cells, for example providing a pathway for phosphate ions during mineralization.
Characterization of a tartrate-resistant acid phosphatase (ATPase) from rat bone: Hydrodynamic properties and N-terminal amino acid sequence
Authors: Ek-Rylander Barbro , Bergman Tomas , Andersson Göran 
Published: February 2010

Abstract
Certain physicochemical properties of rat bone tartrate-resistant acid ATPase (TrATPase), including the size and shape of the enzyme, potential subunit composition, and detergent binding, have been elucidated. SDS-polyacrylamide gel electrophoresis in combination with immunoblot analysis showed that the bone TrATPase has a molecular weight of 33,000 D and is composed of disulfide-linked polypeptides of 20,000 and 16,000 D. The enzyme contains 1.7 mol Fe per mol enzyme. Hydrodynamic studies allowed calculation of the Stokes radius (24 Å), the sedimentation coefficient (3.19S), the partial specific volume (0.748 ml/g), the frictional ratio (0.995), and the axial ratio (1.0). The amount of detergent bound to the protein was determined to 4 mol of Triton X-100 per mol enzyme. The molecular weight of bone TrATPase derived from these parameters was 31,900 D. N-terminal amino acid sequence analysis of the Mr 20,000 subunit indicated a high degree of similarity with TRAP enzymes from spleen, uterus, placenta, hairy cell leukemia, and osteoclastoma.
It is concluded that rat bone TrATPase belongs to the type 5 (tartrate-resistant and purple) acid phosphatase family. The similarities in the N-terminal amino acid sequences, iron content, and physicochemical properties of TRAP enzymes indicate a close structural relationship between type 5 acid phosphatases expressed in different tissues. The findings that TrATPase has a spherical shape and binds low amounts of detergent suggest that the enzyme is a soluble protein, compatible with the view that TrATPase is secreted by the osteoclast.
A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat
Authors: Mueller Martina , Schilling Tobias , Minne Helmut W. , Ziegler Reinhard 
Published: February 2010

Abstract
The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP.
SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP.
Measurement of mechanical properties of bone material in vitro by ultrasound reflection: Methodology and comparison with ultrasound transmission
Authors: Antich Peter P. , Anderson Jon A. , Ashman Richard B. , Dowdey James E. , Gonzales Jerome , Murry Robert C. , Zerwekh Joseph E. , Pak Charles Y. C. 
Published: February 2010

Abstract
An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined.
Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior.
In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method.
The impact of menopausal age on future fragility fracture risk
Authors: Gärdsell Per , Johnell Olof , Nilsson Bo E. 
Published: February 2010

Abstract
Altogether 733 postmenopausal women were interviewed with regard to their age at menopause. Subsequent fragility fractures over an 11 year period were recorded. Fragility fractures had occurred in 212 women. These women had an earlier menopause, but the deviation from the nonfracture group was significant only in those who were &lt;70 years at the beginning of the fracture catchment period. Women 50–69 years of age, in the lowest quartile of menopausal age, sustained 50% more fragility fractures than those in the highest quartile. In older women menopausal age does not predict fragility fractures. Women &lt;70 with an early menopause had a significantly lower initial bone mass.
The role of DNA synthesis in the responses of fetal rat calvariae to cortisol
Authors: Lukert Barbara , Mador Anne , Raisz Lawrence G. , Kream Barbara E. 
Published: February 2010

Abstract
To determine the extent to which the effects of cortisol on collagen synthesis in 21 day fetal rat calvariae are linked to its effects on cell replication, calvariae were cultured for 24–72 h with 0.1 and 1 μM cortisol in the presence or absence of 1 mM hydroxyurea (HU) or 30 μM aphidicolin (APC), inhibitors of DNA synthesis. The incorporation of [3H]proline into collagenase-digestible protein (CDP) and [3H]thymidine into DNA were measured during the last 2 h of culture. At 24 h HU and APC decreased thymidine incorporation by &gt;90%, and this remained low for the duration of culture. In contrast, cortisol reduced thymidine incorporation by only 44% at 72 h. Although cortisol caused a 24 h stimulatory effect and a 48 and 72 h inhibitory effect on CDP labeling and the percentage of collagen being synthesized (PCS), HU, and APC had no effect on basal CDP labeling or PCS over the 72 h culture period. Cortisol caused parallel alterations in the steady-state levels of α-1(I) procollagen mRNA, suggesting that its effects occur at the pretranslational level. At 24 h HU and APC did not prevent the stimulatory effect of cortisol on CDP labeling and PCS. At 48 h the inhibitory effects of cortisol on CDP labeling and PCS were observed in the presence of APC but not in the presence of HU. At 72 h the inhibitory effects of cortisol on CDP labeling and PCS were still observed in the presence of HU and APC. The inhibitory effect of cortisol on CDP labeling was only partially reversed 48 h after removing cortisol from calvariae treated with hormone for 48 h. These data show that DNA synthesis inhibitors by themselves do not mimic the effects of cortisol on collagen synthesis nor do they prevent the early stimulation and the late inhibition of collagen synthesis by cortisol. Thus we conclude that the long-term inhibitory effect of cortisol on collagen synthesis in calvariae is largely independent of cell replication. The component of collagen synthesis that is reversible may represent the direct inhibitory effect of cortisol on differentiated osteoblasts. The nonreversible component of inhibition may be due to a more permanent effect of cortisol on cell populations within the calvariae. One possibility is that cortisol inhibits differentiation of osteoprogenitor cells to the osteoblast lineage leading to decreased osteoblast number and a subsequent inhibition of collagen production.
Serum ionized calcium, as well as phosphorus and parathyroid hormone, is associated with the plasma 1,25-dihydroxyvitamin D3 concentration in normal postmenopausal women
Authors: Dawson-Hughes Bess , Harris Susan , Dallal Gerard E. 
Published: February 2010

Abstract
Serum parathyroid hormone (PTH) and low-normal serum phosphorus (P) concentrations have well-known trophic effects on renal 1-hydroxylase. A role for serum ionized calcium (Ca2+) in the day-to-day regulation of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] has not been identified in normal humans. The associations between serum Ca2+, PTH, P, and plasma 1,25-(OH)2D3 were evaluated in a cross-sectional study of 275 healthy postmenopausal women. Partial correlations of Ca2+, PTH, and P (each controlled for the other two) with 1,25-(OH)2D3 were sought within quintiles of Ca2+ At low-normal concentrations (&lt;1.26 mmol/liter, quintile 1) Ca2+ was inversely correlated with 1,25-(OH)2D3 (rp = -0.30, p = 0.028). At midnormal concentrations Ca2+ was not significantly correlated with 1,25-(OH)2D3. At high-normal concentrations &gt;1.32 mmol/liter, quintile 5) Ca2+ attenuated the positive associations of both PTH and low-normal P with 1,25-(OH)2D3. In quintile 5 Ca2+, PTH, and P together accounted for none of the variability in 1,25-(OH)2D3 (R2 = 0.03, p = 0.671). Women with Ca2+ below 1.32 mmol/liter were next examined by quintile of P. As expected, at low-normal concentrations (&lt;1.03 mmol/liter, quintile 1) P was significantly correlated with 1,25-(OH)2D3 (rp = -0.32, p = 0.047). The association between PTH and 1,25-(OH)2D3 was statistically significant only at midnormal concentrations of P (rp = 0.52, p = 0.001, quintile 3). We conclude that Ca2+, along with PTH and P, is associated with the plasma concentration of 1,25-(OH)2D3 in normal postmenopausal women.
Fecal calcium density: A measure of calcium compliance
Authors: Heaney Robert P. 
Published: February 2010

Abstract
We evaluated fecal calcium density (mass of calcium per g dry weight of feces) as a measure of compliance with a prescribed calcium intake regimen using 4 day fecal pools collected on a metabolic research unit from subjects ingesting measured, constant intakes. Fecal calcium density was highly correlated with intake (r = 0.897, P &lt; 0.001). Intake estimates based on fecal calcium density exhibited a standard error of the mean equal to 3.76 mmol calcium. Since a typical calcium supplement table contains 12.5 mmol calcium, the measurement of fecal calcium density is sensitive enough to detect regular omission of one or more pills daily. Applicability of this approach to convenience samples of feces was evaluated in 15 individuals by testing homogeneity of fecal calcium density values on up to six different 3–9 g portions (wet weight) of each volunteer's fecal sample. The within-sample coefficient of variation was 9.5% for all subsamples and 7.3% for samples from individuals with intakes above 25 mmol calcium per day. Thus feces are reasonably homogeneous in regard to calcium density. Accordingly, reasonably small fecal collections should suffice for its measurement.
Procalcitonin NH2-terminal cleavage peptide has no mitogenic effect on normal human osteoblast-like cells
Authors: Hassager Christian , Bonde Susan K. , Anderson Marlys A. , Rink H. , Spelsberg Thomas C. , Riggs B. Lawrence 
Published: February 2010

Abstract
The NH2-terminal cleavage peptide of procalcitonin (N-proCT) recently was reported to be a bone cell mitogen (Burns DM et al., Proc Natl Acad Sci USA 86:9519–9523, 1989). We have investigated the effect of N-proCT on the proliferation of normal human cells that have the phenotype of mature osteoblasts (hOB cells). N-proCT treatment for 24, 48, or 96 h in concentrations from 1 nM to 1 μM did not significantly increase [3H]thymidine uptake (means ranged from -19% to 38% of control, no significant differences) in hOB cells (6–10 cell strains per experiment) plated at four different densities. However, the hOB cells responded significantly to treatment with transforming growth factor β (3 ng/ml), bovine insulin (300 μg/ml), or 30% fetal calf serum, which were included in all experiments as positive controls. The [3H]thymidine uptake data were confirmed in a direct cell count experiment tested at 96 h. Thus our data do not support the hypothesis that N-proCT is a potent mitogen for normal human osteoblasts.