bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversibility of Calcitriol-Induced Medial Artery Calcification in Rats With Intact Renal Function
Authors: Bas Alicia , Lopez Ignacio , Perez Jose , Rodriguez Mariano , Aguilera-Tejero Escolastico 
Published: April 2006

Abstract
VC is an important clinical entity; however, very little information is available on its resolution. Induction and regression of calcitriol-induced VC was studied in 47 rats. After calcitriol withdrawal, there was a relatively rapid regression of VC mediated by an active cellular process.
Introduction: Vascular calcifications (VCs) represent an important risk factor for cardiovascular death. Although VCs are prevalent in relevant diseases (e.g., chronic kidney disease, osteoporosis, diabetes), the reversibility of extraskeletal calcifications is an unresolved issue. This study was conducted to investigate (1) the in vivo effect of calcitriol on VC and (2) whether calcitriol-induced VC would regress after suppression of calcitriol treatment.
Materials and Methods: The calcifying effect of calcitriol was studied in four groups of rats (n = 8) that received calcitriol (1 μg/kg, IP) for 2, 4, 6, and 8 days. The reversibility of VC was studied in three additional groups (n = 5) treated with 1 μg/kg of calcitriol for 8 days that were subsequently killed 1, 2, and 9 weeks after the last calcitriol dose. Aortic VC was assessed by histology and by quantification of aortic calcium and phosphorus content. The aortic wall was studied by histology and immunohistochemistry. Statistical analysis was performed by ANOVA and t-tests.
Results: Calcitriol administration resulted in a time-dependent induction of VC, with aortic calcium and phosphorus being significantly increased at 6 and 8 days. Treatment with calcitriol for 8 days resulted in massive medial calcification of the aorta with a 10- to 30-fold increase in the aortic Ca and P content. After suppressing calcitriol administration, a progressive decrease in von Kossa staining and aortic Ca (from 32.8 ± 2.5 to 9.3 ± 1.8 mg/g of tissue, p &lt; 0.001) and P (from 11.9 ± 1.2 to 2.7 ± 1.8 mg/g of tissue, p = 0.001) content was evidenced. Histology of the aortic wall showed monocytes adhered to the aortic endothelium and macrophages involved in the reabsorption of calcium deposits.
Conclusions: Our results show that calcitriol treatment induces time-dependent VC. After calcitriol withdrawal, VC regress rapidly with aortic calcium and phosphorus decreasing by 75% in the course of 9 weeks. An active cellular process seems to be involved in regression of VC.
Correcting the Magnification Error of Fan Beam Densitometers
Authors: Griffiths M. R. , Noakes K. A. , Pocock N. A. 
Published: April 2006

Abstract
Dual-energy X-ray absorptiometry (DXA), using a narrow pencil-shaped X-ray beam coupled to a single detector, has been used extensively. More recently, DXA using a fan-shaped X-ray beam coupled to an array of detectors has been introduced. This new generation of scanners causes an inherent magnification of scanned structures as the distance from the X-ray source decreases. This magnification, which occurs in the medial-lateral direction but not in the craniocaudal direction, does not affect bone mineral density (BMD). There are, however, significant changes of bone mineral content (BMC), bone area, and parameters of hip geometry, with varying distance of the bone scanned from the X-ray source. Variability of soft tissue thickness in vivo, by altering the distance of the skeleton from the scanning table and X-ray source, may cause clinically significant errors of BMC, bone area, and proximal femur geometry when measured using fan-beam densitometers. We analyzed the geometry of Lunar and Hologic fan beam scanners to derive equations expressing the true width of scanned structures in terms of the apparent width and machine dimensions. We also showed mathematically that performing an additional scan, at a different distance from the X-ray source than the first scan, provides simultaneous equations that can be solved to derive the real width of a scanned bone. This hypothesis was tested on the Lunar Expert using aluminium phantoms scanned at different table heights. There was an excellent correlation, r = 0.99 (p &lt; 0.001), between the predicted phantom width and the measured phantom width. In conclusion, this study shows that the magnification error of fan beam DXA can be corrected using a dual scanning technique. This has important implications in the clinical usefulness of BMC and geometrical measurements obtained from these scanners.
Fat or Lean Tissue Mass: Which One Is the Major Determinant of Bone Mineral Mass in Healthy Postmenopausal Women?
Authors: Chen Zhao , Lohman Timothy G. , Stini William A. , Ritenbaugh Cheryl , Aickin Mikel 
Published: April 2006

Abstract
The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p &lt; 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p &lt; 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.
[3H]Bradykinin Receptor-Binding, Receptor-Recycling, and Receptor-Internalization of the B2 Bradykinin Receptor in the Murine Osteoblast-like Cell Line MC3T3-E1
Authors: Windischhofer Werner , Leis Hans J. 
Published: April 2006

Abstract
Bradykinin (BK) has been demonstrated to induce inositol phosphate production, release of intracellular Ca2+, and prostaglandin E2 (PGE2) synthesis in the murine osteoblast-like cell line MC3T3-E1. Because cellular response to BK is a function of receptor affinity, receptor coupling, and receptor recycling, we investigated kinetic properties, specificity, and regulation at the BK-receptor level on intact, BK-sensitive MC3T3-E1 cells. Our results clearly demonstrate the existence of a single category of binding sites for [3H]BK (kD = 366 ± 98 pM; Bmax = 45.3 ± 6.6 fmol/mg of protein). Displacement studies with various BK analogs gave a rank order compatible with a B2 BK-receptor type (BK &gt; Lys-BK &gt; [Hyp3]-BK &gt; Met-Lys-BK &gt; HOE140 &gt; Tyr-BK &gt; Tyr8-BK &gt; D-Arg, [Hyp3, Thi5,8, D-Phe7]-BK &gt; [D-Phe7]-BK &gt; des-Arg9-BK &gt; des-Arg9, [Leu8]-BK = angiotensin II). No atypic high-affinity binding sites for the B1 receptor agonist des-Arg9-BK could be observed. Prestimulation of MC3T3-E1 cells with BK resulted in the disappearance of accessible B2 receptors at the cell surface by internalization. Postexposure of BK-pretreated cells to ligand-free medium resulted in almost complete receptor restoration within 30 minutes, exhibiting an intermediate state of two categories of binding sites (kD1 = 444 ± 37 pM, Bmax1 = 9.2 ± 0.3 fmol/mg of protein and kD2 = 2.7 ± 0.28 pM, Bmax2 = 24.2 ± 0.2 fmol/mg of protein), probably representing coupled and uncoupled B2 receptors. Prolonged stimulation with BK (2.5–5 h) also revealed the temporal occurrence of two categories of binding sites after 2.5 h (kD1 = 228 ± 3.5 pM; Bmax1 = 15.6 ± 0.6 fmol/mg of protein; kD2 = 2.7 ± 0.25 nM; Bmax2 = 40.7 ± 1.5 fmol/mg of protein), whereas low-affinity binding sites disappeared after 5 h.
Signal Transduction of Mechanical Stimuli Is Dependent on Microfilament Integrity: Identification of Osteopontin as a Mechanically Induced Gene in Osteoblasts
Authors: Toma C. D. , Ashkar S. , Gray M. L. , Schaffer J. L. , Gerstenfeld L. C. 
Published: April 2006

Abstract
Mechanical perturbation has been shown to modulate a wide variety of changes in second message signals and patterns of gene expression in osteoblasts. Embryonic chick osteoblasts were subjected to a dynamic spatially uniform biaxial strain (1.3% applied strain) at 0.25 Hz for a single 2-h period, and osteopontin (OPN), an Arg-Gly-Asp (RGD)-containing protein, was shown to be a mechanoresponsive gene. Expression of opn mRNA reached a maximal 4-fold increase 9 h after the end of the mechanical perturbation that was not inhibited by cycloheximide, thus demonstrating that mechanoinduction of opn expression is a primary response through the activation of pre-existing transcriptional factors. The signal transduction pathways, which mediated the increased expression of opn in response to mechanical stimuli, were shown to be dependent on the activation of a tyrosine kinase(s) and protein kinase A (PKA) or a PKA-like kinase. Selective inhibition of protein kinase C (PKC) had no effect on the mechanoinduction of osteopontin even though opn has been demonstrated to be an early response gene to phorbol 12-myristate 13-acetate (PMA) stimulation. Mechanotransduction was dependent on microfilament integrity since cytochalasin-D blocked the up-regulation of the opn expression; however, microfilament disruption had no effect on the PMA induction of the gene. The microtubule component of the cytoskeleton was not related to the mechanism of signal transduction involved in controlling opn expression in response to mechanical stimulation since colchicine did not block opn expression. Mechanical stimulus was shown to activate focal adhesion kinase (FAK), which specifically became associated with the cytoskeleton after mechanical perturbation, and its association with the cytoskeleton was dependent on tyrosine kinase activity. In conclusion, these results demonstrate that the signal transduction pathway for mechanical activation of opn is uniquely dependent on the structural integrity of the microfilament component of the cytoskeleton. In contrast, the PKC pathway, which also activates this gene in osteoblasts, acts independently of the cytoskeleton in the transduction of its activity.
Fas and Fas Ligand Interaction Is Necessary for Human Osteoblast Apoptosis
Authors: Kawakami Atsushi , Eguchi Katsumi , Matsuoka Naoki , Tsuboi Masahiko , Koji Takehiko , Urayama Satoshi , Fujiyama Kaoru , Kiriyama Takeshi , Nakashima Tomoki , Nakane Paul K. , Nagataki Shigenobu 
Published: April 2006

Abstract
We investigated the cellular and humoral interactions between peripheral blood mononuclear cells (PBMCs) and human osteoblasts, leading to apoptosis of osteoblasts. Human osteoblastic cell line MG63 and human primary osteoblast-like cells obtained from biopsy specimens were used in this study. PBMCs were isolated from healthy donors and cultured with or without stimulation by recombinant interleukin-2 followed by 12-o-tetradecanoyl-phorbol 13-acetate with ionomycin. Fas was functionally expressed on MG63 and primary osteoblast-like cells. Activated PBMCs expressed Fas ligand (FasL) strongly on their surface and killed MG63 and primary osteoblast-like cells. Cultured supernatants of activated PBMCs also induced apoptotic cell death of MG63 and primary osteoblast-like cells. In contrast, both unstimulated PBMCs and cultured supernatants of unstimulated PBMCs did not induce apoptosis of these cells. Furthermore, the cytotoxic effect and induction of apoptosis against MG63 and primary osteoblast-like cells by activated PBMCs and cultured supernatants were inhibited significantly by human Fas chimeric protein. Our data showed that human osteoblasts expressed Fas fuctionally and both membrane-type and soluble form FasL from activated PBMCs induced apoptosis of these cells, providing the one possible mechanism of bone loss in inflammatory diseases such as rheumatoid arthritis.
Phosphorylation of the Human Calcitonin Receptor by Multiple Kinases Is Localized to the C-Terminus
Authors: Nygaard Sean C. , Kuestner Rolf E. , Moore Emma E. , Stroop Steven D. 
Published: April 2006

Abstract
The calcitonin receptor is a seven-transmembrane G-protein coupled receptor which is located on osteoclasts, in kidney, and in brain. The receptor signals through multiple pathways, including activation of adenylate cyclase, leading to inhibition of bone resorption. In the present study, we used antibodies raised against the C-terminus of the human calcitonin (CT) receptor to study receptor phosphorylation. In baby hamster kidney cells transfected with the human CT receptor, phosphorylation of the receptor increased approximately 2.5-fold after cells were treated with calcitonin, phorbol ester, forskolin, or calcitonin plus phorbol ester. Phosphorylation reached a maximum 20 minutes after treatment with sCT and half-maximal phosphorylation was observed at 0.1 nM sCT, a hormone concentration related to receptor occupancy. Digestion of the immunoprecipitated receptor with cyanogen bromide (CNBr) yielded a single32P-labeled fragment which migrates at Mr 14 kD on gel electrophoresis. This corresponds to the predicted size of the CNBr fragment containing the C-terminal domain of the receptor. No32P-labeled bands were observed for CNBr fragments predicted to contain the first, second, or third intracellular loops. An identical labeling pattern was seen with cells expressing an alternatively spliced isoform of the human receptor (insert-positive isoform). Phosphorylation of the receptor by phorbol ester and forskolin was further localized to a Mr 6 kD proteolytic fragment within the C-terminus. The protein kinase A and C inhibitors staurosporine, chelerythrine, and H-89 had little effect on CT-induced phosphorylation, suggesting that nonsecond messenger-activated kinases are involved in hormone-dependent CT receptor phosphorylation.
A Collagenous Cementum-Derived Attachment Protein Is a Marker for Progenitors of the Mineralized Tissue-Forming Cell Lineage of the Periodontal Ligament
Authors: Liu Hong Wei , Yacobi Rinat , Savion Naphtali , Narayanan A. Sampath , Pitaru Sandu 
Published: April 2006

Abstract
The periodontal ligament (PDL) is a fibrous and cellular connective tissue that mediates tooth attachment to bone, and it comprises fibroblastic and mineralized tissue-forming (MTF) progenitors. The MTF progenitors are believed to give rise to the cementoblastic and osteoblastic lineages. Cementum attachment protein (CAP) is a collagenous cementum-derived protein which binds strongly to osteoblasts, moderately to PDL cells, and weakly to gingival fibroblasts. The aim of the present study was to determine the relationship between the capacity of PDL progenitors to bind CAP and their potential to express alkaline phosphatase (ALP) and form mineralized-like tissue in culture. Cloned human PDL progenitor populations obtained from nine human donors were assayed for their constitutive capacity to bind CAP and express ALP, and for the dexamethasone-induced potential to form mineralized-like tissue in culture in the presence of ascorbic acid and β-glycerophosphate. Forty percent of the progenitor clones produced mineralized-like tissue. Two patterns of mineralization were observed: a spread and flat pattern similar to that produced by human bone cells in culture and a nodular ridge–like type resembling that formed by human cementoma-derived cells. A direct correlation was found between the percentage of ALP positive cells in each progenitor clone and the amount of mineralized-like tissue formed (r = 0.565). Similar correlations were found between the number of ALP positive cells and the binding capacity of each clone (r = 0.392) and between the CAP binding capacity and mineralized-like tissue formation (r = 0.584). Multiple regression analysis indicated that the constitutive capacity of a clone to bind CAP and express ALP is directly correlated to its dexamethasone-induced potential to form mineralized tissue (r = 0.675). These results indicate that CAP binding and ALP expression can serve as markers for the identification of MTF progenitors in the heterogeneous cultured population of the human periodontal ligament. These data show for the first time that binding capacity to extracellular components of mineralized tissues can be a marker for mineralized tissue-forming progenitors.
Evidence for Increased Bone Formation Following a Brief Endurance-Type Training Intervention in Adolescent Males
Authors: Eliakim Alon , Raisz Lawrence G. , Brasel Jo Anne , Cooper Dan M. 
Published: April 2006

Abstract
The effect of exercise training, particularly relatively brief periods, on bone turnover markers in adolescents has been poorly studied. Thirty-eight healthy males (16 ± 0.7 years) participated in a 5-week summer school program in which 20 subjects were randomly assigned to a training group consisting of 2 h/day, 5 days/week of endurance exercise, and 18 subjects were assigned to a control group. Bone formation was assessed by measurements of circulating osteocalcin, bone-specific alkaline phosphatase (BSAP), and the C-terminal procollagen peptide (PICP). Bone resorption was assessed by urinary levels of free deoxypyridinoline cross-links (dPYR) and the C-(CTX) and N-terminal (NTX) telopeptide cross-links. Prior to training, there was a weak positive correlation between fitness and PICP (r = 0.27, p &lt; 0.05), but no correlations were observed between fitness and either the other markers of bone formation or bone resorption. Training led to a significant increase in (1) osteocalcin (15 ± 4%, p &lt; 0.03), (2) BSAP (21 ± 6%, p &lt; 0.02), and (3) PICP (30 ± 11%, p &lt; 0.03) and to a significant decrease in NTX (−21 ± 3%, p &lt; 0.05). These bone turnover markers did not change in the control subjects (osteocalcin, 0 ± 4%; BSAP, 2 ± 4%; PICP, −4 ± 6%; NTX, −6 ± 4%). There was no change in urinary dPYR and CTX in either control or trained subjects. Fitness is only weakly, if at all, correlated with bone formation, but a relatively brief period of endurance training leads to a substantial increase in bone formation markers in adolescent males. School-based, short-term exercise training programs could play a role in enhancing bone formation in adolescents.
Long-Term Effects of Intravenous Pamidronate in Fibrous Dysplasia of Bone
Authors: Chapurlat Roland D. , Delmas Pierre D. , Liens Daniel , Meunier Pierre J. 
Published: April 2006

Abstract
Fibrous dysplasia of bone (FD) is a rare disorder characterized by proliferation of fibrous tissue in bone marrow leading to osteolytic lesions. It causes bone pain and fractures. To date the only treatment is orthopedic. Histological and biochemical similarities between FD and Paget's bone disease related to increased osteoclastic resorption led us to propose treatment with the bisphosphonate pamidronate. The aim of the study was to assess the long-term effects of intravenous pamidronate in FD. In this open label phase III study, 20 patients with FD (11 males and 9 females; mean age 31 years) received courses of 180 mg of intravenous pamidronate every 6 months (60 mg/day during 3 days by infusion). The mean duration of follow-up was 39 months (range 18–64). Severity of bone pain, number of painful skeletal sites per patient, X-rays of all involved areas, serum alkaline phosphatase, fasting urinary hydroxyproline, and urinary type I collagen C-telopeptide were assessed every 6 months. The severity of bone pain and the number of painful sites appeared to be significantly reduced. All biochemical markers of bone remodeling were substantially lowered. We observed a radiographic response in nine patients with refilling of osteolytic lesions. A mineralization defect proven by bone biopsy was observed in one case. Four patients sustained bone stress lines, but no fracture occurred. We suggest that intravenous pamidronate alleviates bone pain, reduces the rate of bone turnover assessed by biochemical markers, and improves radiological lesions of FD. Few side effects were observed.
Appendicular Bone Mass in Children with a High Prevalence of Low Dietary Calcium Intakes
Authors: Pettifor John M. , Moodley Gopal P. 
Published: April 2006

Abstract
We have previously documented evidence of dietary calcium deficiency in black children living in a rural community in the eastern part of South Africa. The present study determined the bone mass of the distal one-third of the radius in a random sample of children living in the same community and compared their bone mass measurements with those of black children living in a similar rural community but without evidence of dietary calcium deficiency. Further, factors (weight, height, serum corrected total calcium, phosphorus, and alkaline phosphatase [ALP]) that might influence appendicular bone mass were assessed and correlated with the bone mass measurements. A random sample of 306 boys and 345 girls between the ages of 1 and 20 years were included in the study. Hypocalcemia was found in 6.5% of the boys and 5% of the girls, while elevated ALP values were recorded in 20 and 26% of the boys and girls, respectively. After adjusting for differences in age, weight, and height, bone mineral density (BMD) and bone mineral apparent density (BMAD) were significantly lower and bone width (BW) greater in study than control children. In a stepwise regression analysis, weight and/or height accounted for the majority of the observed variance in BMC, BW, and BMD; however, a significant effect of serum calcium (positively) and ALP (negatively) on BMC and BMD was also found. In boys, but not girls, serum ALP also had a positive effect on BW. BMAD was negatively correlated to ALP and positively correlated to serum calcium in both boys and girls. Those children with hypocalcemia or elevated ALP levels had significantly lower BMC, BMD, and BMAD and a trend toward greater BW than children with normal biochemistry. The findings suggest that low dietary calcium intake may have a detrimental effect on appendicular bone density in rural black children. Whether or not these effects are disadvantageous in the long-term is not known.
The Short-Term Effects of Cisplatin Chemotherapy on Bone Turnover
Authors: Young David R. , Virolainen Petri , Inoue Nozomu , Frassica Frank J. , Chao Edmund Y. S. 
Published: April 2006

Abstract
Cisplatin is an effective agent in the treatment of osteosarcoma of bone but little is known of its effects on normal bone turnover. Twenty-four dogs divided into three study groups were used to study the effect of cisplatin on normal bone turnover at the distant site of surgery. Group 1 served as the control group, group 2 received four cycles of cisplatin every 3 weeks before the surgery, and group 3 received four cycles postoperatively. The bone turnover rate was evaluated by measuring levels of systemic bone markers, osteocalcin, alkaline phospohatase, urine pyridinoline cross-links, and by determination histomorphometric indices. Histomorphological analysis showed poor correlation on bone formation with systemic bone markers at distant sites of surgery. Histomorphometrically normal bone turnover was affected by administration of cisplatin, but the effect was temporary, late, and less significant than what occurred at the surgical site. Our data showed that significant effects of cisplatin are observed at the site of active cellular induction and proliferation, such as implant-host interface, and less effects are seen at the sites of normal bone turnover.