bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Muscle Mass With Myostatin Deficiency Improves Gains in Bone Strength With Exercise
Authors: Hamrick Mark W , Samaddar Ted , Pennington Catherine , McCormick John 
Published: April 2006

Abstract
We tested the hypothesis that increased muscle mass augments increases in bone strength normally observed with exercise. Myostatin-deficient mice, which show increased muscle mass, were exercised along with wildtype mice. Results indicate that increases in bone strength with exercise are greater in myostatin-deficient mice than in wildtype mice, suggesting that the combination of increased muscle mass and physical activity has a greater effect on bone strength than either increased muscle mass or intense exercise alone.
Introduction: Muscle (lean) mass is known to be a significant predictor of peak BMD in young people, and exercise is also found to increase bone mass in growing humans and laboratory animals. We sought to determine if increased muscle mass resulting from myostatin deficiency would enhance gains in bone strength that usually accompany exercise.
Materials and Methods: Male mice lacking myostatin (GDF-8) were used as an animal model showing increased muscle mass. Wildtype and myostatin-deficient mice (n = 10-12 per genotype) were exercised on a treadmill for 30 minutes/day, 5 days/week, for 4 weeks starting at 12 weeks of age. Caged wildtype and myostatin-deficient mice (n = 10-12 per genotype) were included as sedentary controls. Structural and biomechanical parameters were measured from the radius.
Results: Ultimate force (Fu), displacement (Du), toughness (energy-to-fracture; U), and ultimate strain (εu) increased significantly with exercise in myostatin-deficient mice but not in normal mice. When Fu is normalized by body mass, exercised myostatin-deficient mice show an increase in relative bone strength of 30% compared with caged controls, whereas exercised wildtype mice do not show a significant increase in ultimate force relative to caged controls. Relative to body weight, the radii of exercised myostatin-deficient mice are &gt;25% stronger than those of exercised normal mice.
Conclusions: Increased muscle mass resulting from inhibition of myostatin function improves the positive effects of exercise on bone strength.
Biochemical Markers of Bone Resorption Compared with Estimates of Bone Resorption from Radiotracer Kinetic Studies in Osteoporosis
Authors: Dr. Eastell R. , Colwell A. , Hampton L. , Reeve J. 
Published: April 2006

Abstract
The pyridinium cross-links of collagen pyridinoline (Pyd) and deoxypyridinoline (Dpd) are released during bone resorption and are neither metabolized nor absorbed from the diet. The aim of this study was to validate their use in osteoporosis. We studied 19 women with osteoporosis and estimated the bone resorption rate from a combined calcium balance/kinetics technique without (R) and with partial (RH) and “complete” (Res) correction for long-term exchange. The strongest correlation was observed between the bone-specific marker (Dpd) and with complete correction for long-term exchange (Res) (r = 0.71, p &lt; 0.001). The intercept was not different from zero, suggesting that bone was the major source for Dpd. The crude ratio of Dpd to Res in the 19 women was 54.5; but the regression coefficient relating Dpd as the dependent variable to Res was 31.8 (95% CI 15.6–48.0), which was higher, but not significantly, than the ratio between Dpd and calcium (16.4) in 10 bone samples (cortical and trabecular bone). The weakest correlations between a biochemical marker and a kinetic index were those between hydroxyproline (a nonspecific marker of bone resorption) and R or RH. Treatment with hormone replacement therapy (HRT) or HRT and parathyroid hormone peptide 1–38 in seven women over 1 year resulted in similar percent changes in the biochemical markers and estimates of bone resorption. We conclude that the measurement of Dpd provides a reasonably accurate assessment of bone resorption in osteoporosis, and in the context of several repeat 24-h collections of urine offers measurement precision that is similar to that obtainable with methods depending on the use of radioisotopic tracers and the assessment of metabolic calcium balance.
Enhanced Nonsaturable Calcium Transport in the Jejunum of Rats During Lactation, but Not During Pregnancy
Authors: Boass Agna , Toverud Svein U. 
Published: April 2006

Abstract
The lactating (L) rat loses in excess of 100 mg of calcium (Ca) per day to milk at peak lactation. Most of the Ca must be provided by increased intestinal absorption. In an effort to examine adaptation of intestinal calcium absorption during lactation, nonsaturable absorption from the small intestine of rats was calculated from the disappearance of Ca from in situ ligated loops of jejunum during the last week of pregnancy and throughout lactation and weaning. Efficiency of absorption is reflected by the slope of the regression line of Ca absorbed on Ca introduced into the loop. Absorption of Ca in the jejunum was markedly enhanced starting at 5 days of lactation and for the remainder of lactation. Two days after weaning, the efficiency of jejunal Ca absorption decreased to the nonmated (NM) control level, while the lactation-associated intestinal hypertrophy persisted beyond 2 days postweaning. The percentages of water and Ca absorbed were positively and significantly correlated in both L and NM rats. In contrast to Ca, magnesium (Mg) and strontium (Sr) transport from ligated loops were not enhanced during lactation. Fifty millimolar glucose in the test solution increased the absorption of both water and Ca, but not Mg, from jejunal loops of NM rats. Glucose increased Ca absorption in NM rats up to the level seen in L rats. Glucose did not increase Ca absorption further in L rats, perhaps because of the greater availability of glucose to the intestine during lactation. We conclude that in rats the efficiency of nonsaturable Ca absorption from the jejunum is significantly increased during well established lactation, but not during pregnancy. The underlying mechanism appears to be specific for Ca, may be dependent on glucose, and is unrelated to intestinal hypertrophy.
Growth Hormone Normalizes Renal 1,25-Dihydroxyvitamin D3-24-Hydroxylase Gene Expression but Not Na+-Phosphate Cotransporter (Npt2) mRNA in Phosphate-Deprived Hyp Mice
Authors: Roy Stéphane , Martel Josée , Tenenhouse Harriet S. 
Published: April 2006

Abstract
The murine X-linked Hyp mutation is characterized by decreased renal expression of type II Na+-phosphate (Pi) cotransporter (Npt2) mRNA and an abnormal vitamin D response to Pi deprivation. The latter is manifest by an aberrant fall in serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D) levels that is associated with an increase in renal 1,25(OH)2D-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway. Because growth hormone (GH) enhances renal Na+-Pi cotransport and permits the adaptive 1,25(OH)2D response in Pi-deprived hypophysectomized rats, we examined the effects of GH on vitamin D metabolism and renal Npt2 mRNA abundance in Hyp mice fed control and low Pi diets. GH significantly decreased renal 24-hydroxylase activity (0.202 ± 0.020 to 0.098 ± 0.008 pmol/mg of protein/minute, p &lt; 0.05) and mRNA abundance, relative to β-actin mRNA (299 ± 13 to 78 ± 14, p &lt; 0.05), in Hyp mice fed the low Pi diet but had no effect on either parameter in mutants fed the control diet. Moreover, after GH treatment, renal 24-hydroxylase gene expression was no longer elevated in Pi-deprived Hyp mice relative to mutants fed control diet. In contrast, GH did not correct the serum concentration of 1,25(OH)2D in Pi-deprived Hyp mice. We also demonstrate that GH did not normalize renal Npt2 mRNA expression, relative to β-actin mRNA, in Hyp mice fed either control or low Pi diets. The present data demonstrate that normalization of renal 24-hydroxylase gene expression in Pi-deprived Hyp mice by GH is not sufficient to correct the serum concentration of 1,25(OH)2D and is not associated with an alteration in renal Npt2 mRNA expression.
Long-Term Treatment of Indomethacin Reduces Vertebral Bone Mass and Strength in Ovariectomized Rats
Authors: Saino Hitoshi , Matsuyama Toshikatsu , Takada Junichi , Kaku Tohru , Ishii Seiichi 
Published: April 2006

Abstract
We investigated the effect of the long-term treatment of indomethacin, on lumbar spinal bone mineral density (LSBMD), cancellous bone mass, structure, and strength of vertebral body in old ovariectomized (OVX) rats. Ten-month-old female Wistar rats were divided into five groups: the sham operated + vehicle (sham+VEH) group, the OVX + vehicle (OVX+VEH) group, the OVX + indomethacin (IN) 1.5 mg/kg/week (OVX+IN1.5) group, the OVX + IN 6.0 mg/kg/week (OVX+IN6.0) group, and the OVX + IN 15.0 mg/kg/week (OVX+IN15.0) group. IN or vehicle were given by subcutaneous injection (sc) three times per week. The treatments were started at 1 week after operation and continued for 24 weeks. LSBMD(L2–L5) was measured at 0, 12, and 24 weeks after the beginning of treatment. At the end of the experimental period, the animals were sacrificed, and bone histomorphometrical and biomechanical analysis of lumbar vertebral body were done. LSBMD, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) decreased significantly in a dose-related manner with IN. In the OVX+IN15.0 group, LSBMD decreased by 12.7%, BV/TV decreased by 65.5%, and Tb.Th decreased by 32.8%, compared with the OVX+VEH group. In addition, the maximum stress in a compressive mechanical test of L4 vertebral body in OVX groups was also decreased in a dose-related manner with IN, and this value in the OVX+IN15.0 group was 31.3% lower than in the OVX+VEH group. We conclude that long-term treatment with IN accentuated the OVX-related decrease in trabecular bone mass and the compressive strength of lumbar vertebrae.
Comparison of Bone Density Measurement Techniques: DXA and Archimedes' Principle
Authors: Keenan Michael J. , Hegsted Maren , Jones Karen L. , Delany James P. , Kime James C. , Melancon Louis E. , Tulley Richard T. , Hong Kelly D. 
Published: April 2006

Abstract
The standard method for determination of density (g/cm3) of bones from small animals has been the application of Archimedes' principle. A recent development has been software for the determination of “density” (g/cm2) of small animal bones with dual-energy X-ray absorptiometry (DXA). We compared Archimedes' principle and DXA (Hologic QDR-2000) in the measurement of the densities of whole and hollowed femurs of 5- to 6-month-old retired female breeder rats. In an attempt to ensure detectable treatment differences, rats were used from a low-vitamin D Holtzman and a supplemental-vitamin D Sprague-Dawley colony. Whole femur densities were higher for supplemental-vitamin D colony rats than for low vitamin D rats using both techniques (Archimedes' principle, p &lt; 0.002; DXA, p &lt; 0.005), and the densities from the two techniques were highly correlated (r = 0.82, p &lt; 0.0001). Actual density values were higher for Archimedes' principle than for DXA. Other variables such as femur ash weight and calcium content were also highly correlated to densities with both techniques. Hollowed femur density values were higher than whole femur values with Archimedes' principle but lower with DXA. Colony effects for hollowed femur densities were diminished with Archimedes' principle (p &lt; 0.03) and eliminated with DXA (p &lt; 0.53). Investigation of whole bones is more biologically relevant, and both techniques were effective in detecting differences between whole femurs from low-vitamin D and supplemental-vitamin D colony rats.
Calcitonin Alters Bone Quality in Beagle Dogs
Authors: Pienkowski David , Doers Thomas M. , Monier-Faugere Marie-Claude , Geng Zhaopo , Camacho Nancy P. , Boskey Adele L. , Malluche Hartmut H. 
Published: April 2006

Abstract
Because of its antiresorptive properties, calcitonin is widely used to prevent and treat osteoporosis. A stimulatory effect of calcitonin on osteoblasts has also been reported; however, a recent histologic study points to a negative effect of calcitonin on mineralization of cancellous bone. The present experiment was performed to determine whether the observed histological signs of alterations in mineralization are also observed in cortical bone and whether this results in changes in mechanical properties, mineral densities, or mineral properties of canine bone. Sixteen female adult beagle dogs were randomly allocated to receive either human calcitonin at a dose of 0.25 mg/dog (50 IU, n = 8) or vehicle (mannitol, n = 8) every other day for 16 weeks. At the end of the study, the dogs were euthanized. Both tibiae, L1 and L5 vertebrae, and iliac crest bone samples were excised and defleshed. Torsional mechanical properties of tibial diaphyses and compressive strengths of vertebrae were measured. Bone mineral densities (BMD) of tibiae and vertebrae were measured by using dual-energy X-ray absorptiometry. Ultrastructural mineral characteristics of iliac crest bone were determined by gravimetry and Fourier transform infrared spectroscopy (FTIR). Bone histomorphometry was performed in the cortical envelope of the iliac crest. Tibiae from dogs treated with calcitonin withstood significantly less maximum torque until failure, required less torsional energy to reach the maximum torque, and had less torsional stiffness than the tibiae from dogs treated with vehicle (p &lt; 0.05). Cancellous cores of vertebrae from calcitonin-treated dogs withstood less compressive mechanical loading than did vertebral cores from vehicle-treated animals (p &lt; 0.05). Dogs treated with calcitonin had less BMD of both tibiae and vertebrae than vehicle-treated animals (p &lt; 0.05). Bones from calcitonin-treated dogs had significantly less ash content, which correlated with the lower phosphate-to-amide I (detected by FTIR) and greater carbonate-to-phosphate ratios than did bones from vehicle-treated dogs (p &lt; 0.05). Calcitonin-treated dogs exhibited a decrease in bone formation and mineralization rates and an increase in mineralization lag time. These results point to a negative effect of calcitonin on bone quality. These findings are intriguing and call for further studies addressing whether the observed abnormalities are transient or permanent.
Reflection Ultrasound Velocities and Histomorphometric and Connectivity Analyses: Correlations and Effect of Slow-Release Sodium Fluoride
Authors: Zerwekh Joseph E. , Antich Peter P. , Mehta Shreefal , Sakhaee Khashayar , Gottschalk Frank , Pak Charles Y. C. 
Published: April 2006

Abstract
To better understand how structural and functional bone properties contribute to the changes in bone biomechanical properties revealed by ultrasound critical angle reflectometry (UCR) analysis, we measured both UCR velocities and histomorphometric properties in bone biopsy specimens from 33 osteoporotic patients before and following intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate administration. Mean skeletal fluoride exposure was 17 months, and mean skeletal fluoride content was 0.203 ± 0.088 SD% bone ash. Intermittent SRNaF and continuous calcium citrate promoted significant increases in trabecular thickness (122 ± 18 SDμm to 131 ± 20, p = 0.020), mineral apposition rate (0.79 ± 0.26 to 1.05 ± 0.40 μm/day, p = 0.014), and a significant decline in eroded surface (3.9 ± 1.6 to 2.8 ± 1.4%, p = 0.002). There were also significant increases in node number (0.193 ± 0.100 to 0.368 ± 0.245, p &lt; 0.01) and node-to-node strut length (0.076 ± 0.087 to 0.191 ± 0.173, p &lt; 0.01) relative to total cancellous area. Cortical UCR velocity did not change but cancellous velocity significantly increased by 97 m/s following therapy (p = 0.0005). When compared against the significant changes in bone histomorphometry and connectivity, the sum of both cancellous and cortical ultrasound velocities was significantly correlated with node number/area (R2 = 0.305, p &lt; 0.0001) and node-to-node strut length/area (R2 = 0.372, p &lt; 0.0001) and to a lesser extent with mineral apposition rate (R2 = 0.106, p = 0.032). Multiple regression analysis demonstrated that 40% of the variance in the sum of the UCR velocities can be accounted for by the variability in these histomorphometric and connectivity parameters. There were no significant correlations between the sum of cortical and cancellous ultrasound velocities and cancellous bone volume (R2 = 0.014, p = 0.533), trabecular thickness (R2 = 0.012, p = 0.47), or bone mineral density (R2 = 0.003, p = 0.80). These observations indicate that velocity measurements with the UCR methodology show an improvement in bone elasticity associated, in part, with an improvement in the rate of bone mineralization and an improvement in bone quality at the structural level as shown by microarchitecture.
Temporal Changes of mRNA Expression of Matrix Proteins and Parathyroid Hormone and Parathyroid Hormone–Related Protein (PTH/PTHrP) Receptor in Bone Development
Authors: Kondo Hisatomo , Ohyama Takashi , Ohya Keiichi , Kasugai Shohei 
Published: April 2006

Abstract
Expression of parathyroid hormone and parathyroid hormone–related protein (PTH/PTHrP) receptor is one of the osteoblastic phenotypes; however, it has not been clear whether this phenotype expression is a marker of immature or mature osteoblasts. We examined the temporal expression pattern of PTH/PTHrP receptor in bone development in vivo and in vitro compared with the expression of other osteoblastic phenotypes: osteopontin (OPN), bone sialoprotein (BSP) and osteocalcin (OC), alkaline phosphatase (ALP), and mineralization. Total RNA was extracted from rat calvariae, and cell culture of rat bone marrow at different developmental stages and then Northern blot hybridization were performed. Mineralization was detected with contact microradiography (CMR) in calvaria or with Alizarin Red S staining in bone marrow cell culture. Both in calvaria and in marrow cell culture, extensive expression of OPN, BSP, type I collagen (COL I), and ALP coincided with the onset of mineralization, and OC expression was observed after mineralized tissue formation. Notably, PTH/PTHrP receptor was expressed at an early developmental stage (prenatal day 14 in calvaria, day 5 in culture) when mineralized tissue was not formed and other osteoblastic phenotypes were scarcely detected. Further study in cell culture revealed that the fold increase in cyclic adenosine monophosphate (cAMP) in response to PTH was elevated with the advance in the culture stage. These results indicate that mRNA expression of PTH/PTHrP receptor could be the early differentiation marker in osteoblastic lineage and that the levels of cAMP production in response to PTH represent the stage of osteoblastic differentiation.
Rapid Protein Kinase A—Mediated Activation of Cyclic AMP-Phosphodiesterase by Parathyroid Hormone in UMR-106 Osteoblast-like Cells
Authors: Ahlström Mikael , Dr. Lamberg-Allardt Christel 
Published: April 2006

Abstract
Parathyroid hormone (PTH) plays an essential role in osteoblast proliferation and differentiation. The effects of PTH are known to be mediated by cyclic adenosine monophosphate (cAMP) and calcium and by the activation of protein kinase C (PKC). cAMP is hydrolyzed to the inactive form 5′ AMP by cyclic nucleotide phosphodiesterases (PDEs). We have investigated the role of PTH on PDE regulation in UMR-106 osteoblast-like cells. Treatment with 10 nM PTH caused a 3-fold increase in the PDE activity. The activation of PDE could be seen within 2 minutes and reached maximal levels after 20 minutes. The PTH effect was dose dependent with a half-maximal dose of 2 nM. The effect of PTH could be mimicked by the cAMP analogs Bt2 cAMP and forskolin, but not by PTH fragment 3–34, calcium ionophore A23187, or by the PKC activator phorbol 12-myristate 13-acetate. The PDE activity stimulated by PTH could be abolished by the PKA inhibitor H-8. The PDE activated by PTH was inhibitable by low concentrations of the cAMP-PDE–specific inhibitor RO 20-1724 (IC50 = 0.2 μM), but not by low concentrations of the inhibitors of cGMP-stimulated and cGMP-inhibited PDEs MEP-1 and milrinone (IC50 for both compounds &gt;30 μM). The PTH-stimulated cAMP accumulation was potentiated about 7-fold in the presence of RO 20-1724. H-8 potentiated the PTH-stimulated cAMP accumulation about 4-fold. Our results show that PTH rapidly stimulates the activity of cAMP-PDE in UMR-106 cells. The PDE activation involves cAMP and PKA. Inhibition of PKA can abolish the PTH-stimulated PDE activation and leads to increased accumulation of intracellular cAMP.
Establishment and Characterization of Conditionally Immortalized Stromal Cell Lines from a Temperature-Sensitive T-Ag Transgenic Mouse
Authors: Feuerbach Dominik , Loetscher Erika , Buerki Kurt , Sampath T. K. , Dr. Feyen Jean H. M. 
Published: April 2006

Abstract
We established bone marrow stromal cell lines from a transgenic mouse that harbors a temperature-sensitive mutant of the simian virus 40–derived large T-antigen under the control of an major histocompatibility complex (MHC) I promotor. These cell lines were screened for their ability to induce the formation of osteoclasts in a spleen cell/stromal cell coculture system. By means of this screen, five clones, referred to as marine bone marrow stromal clone 1 (mBMS-B1) mBMS-B2, mBMS-B14, mBMS-B18, and mBMS-B21, were selected for detailed characterization. Cell growth depends on culture conditions, i.e., cells grow at 33°C in the presence of murine interferon-γ, whereas cell proliferation ceases at 39°C. The phenotype of the cells is also correlated with the culture conditions because the osteoclast inductive capacity is only seen at 39°C, indicating that the cells undergo differentiation when the transforming agent is inactivated. These conditionally immortalized stromal cells can be induced to express a variety of markers that are typical for mature osteoblasts, e.g., alkaline phosphatase activity and expression of functional parathyroid hormone receptor after stimulation with soluble osteogenic protein 1 (sOP-1). mRNA analysis revealed the expression and regulation of osteopontin, osteonectin, and collagen α1(I) as well as the inducibility of osteocalcin upon treatment with sOP-1. The cells have the potential to form mineralized nodules in supplemented medium. We observed expression of vascular cell adhesion molecule-1, which is stimulated upon treatment of the cells with 1α,25-dihydrocholecalciferol after 4 days, indicating the presence of the receptor for this steroid. These cell lines represent a model to study mechanisms and factors involved in osteoblast differentiation.