bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human protein tyrosine phosphatase-σ: Alternative splicing and inhibition by bisphosphonates
Authors: Endo Naoto , Rutledge Su Jane , Opas Evan E. , Vogel Robert , Rodan Gideon A. , Schmidt Azriel 
Published: February 2010

AbstractTwo forms of the transmembrane human protein tyrosine phosphatase (PTPσ), generated by alternative splicing, were identified by cDNA cloning and Northern hybridization with selective cDNA probes. The larger form of PTPσ is expressed in various human tissues, human osteosarcoma, and rat tibia. The hPTPσ cDNA codes for a protein of 1911 amino acid residues and is composed of a cytoplasmic region with two PTP domains and an extracellular region that can be organized into three tandem repeats of immunoglobulin-like domains and eight tandem repeats of fibronectin type III-like domains. In the brain, the major transcript of PTPσ is an alternatively spliced mRNA, in which the coding region for the fibronectin type III-like domains number four to seven are spliced out, thus coding for a protein of 1502 amino acid residues similar to the rat PTPσ and rat PTP-NE3. Using in situ hybridization, we assigned hPTPσ to chromosome 6, arm 6q and band 6q15. The bacterial-expressed hPTPσ exhibits PTPase activity that was inhibited by orthovanadate (IC50 = 0.02 μM) and by two bisphosphonates used for the treatment of bone diseases, alendronate (ALN) (IC50 = 0.5 μM) and etidronate (IC50 = 0.2 μM). In quiescent calvaria osteoblasts, micromolar concentrations of vanadate, ALN and etidronate stimulate cellular proliferation. These findings show tissue-specific alternative splicing of PTPσ and suggest that PTPs are putative targets of bisphosphonate action.
Expression of rat bone sialoprotein promoter in transgenic mice
Authors: Chen Jinkun , Thomas Huw F. , Jin Hangqing , Jiang Heping , Sodek Jaro 
Published: February 2010

Abstract
Bone sialoprotein (BSP) is a major protein of the mineralized bone extracellular matrix that has been implicated in the nucleation of hydroxyapatite crystals. Our previous studies have demonstrated that BSP mRNA is expressed by differentiated osteoblasts, odontoblasts, and cementoblasts involved in de novo mineralized tissue formation in a tissue-specific and developmentally regulated manner. To determine the basis of the selective expression of the BSP gene, we have generated four transgenic mouse lines in which ∼2.7 kb of the rat BSP promoter ligated to a luciferase reporter gene has been stably integrated into the mouse genome. Assays of luciferase activities in 5-day-old animals has revealed consistently high levels in bone tissues with negligible activities in various other organs including kidney, liver, stomach, intestine, and spleen. In some animals, variable expression was observed in brain and skin. Temporal analyses revealed the highest luciferase expression in neonatal bones, with expression decreasing markedly with subsequent growth and development, as observed previously for the endogenous gene in rats. Immunohistochemical analysis of luciferase activity and in situ hybridization of luciferase mRNA in bone tissues show that differentiated osteoblasts express the highest levels of luciferase, consistent with the induction of endogenous gene expression. These studies demonstrate that the regulation of the BSP gene during osteoblastic differentiation, together with its tissue-specific, developmentally regulated expression, is primarily mediated within the ∼2.7 kb region of the promoter.
Altered trabecular architecture induced by Corticosteroids: A Bone Histomorphometric Study
Authors: Chappard D. , Legrand E. , Basle M.F. , Fromont P. , Racineux J.L. , Rebel A. , Audran M. 
Published: February 2010

Abstract
Prolonged corticosteroid (CS) therapy induces osteoporosis and fractures. Osteoporosis is characterized at the histomorphometric level by reduced bone volume (BV/TV) and disruption of the three-dimensional (3D) trabecular architecture. Several stereological methods have been proposed to characterize these alterations: measurements of trabecular thickness and trabecular number, star volumes, interconnectivity index (ICI) of the bone marrow spaces, and trabecular bone pattern factor (TBPf). These methods were computerized with a single program running on an image analyzer to evaluate the bone changes in a series of iliac biopsies performed on 31 male patients. All of them were asthmatic and had received CS for a long period of time. BV/TV was reduced when compared with age-matched controls. In the CS-treated population, exponential relationships were obtained between bone volume and the different connectivity parameters. The various methods used to measure connectivity were well correlated. When the population was divided into two groups (BV/TV greater or less than an 11% threshold), the architectural disturbances were found to imply two mechanisms. A progressive decline in trabecular thickness was noted in both groups versus controls. Trabecular perforations were not established in the group with BV/TV &gt; 11% with the star volume or ICI, although some alterations were detected by trabecular bone pattern factor measurement. However, perforations were revealed in the group with BV/TV &lt; 11% by all the different methods. Perforations seemed to occur when the trabecular thickness was below 70 μm. This strongly suggests that bone histomorphometry should take into consideration bone volume in combination with detailed 3D descriptors of the trabecular architecture. Several histological methods need to be used in combination to appreciate the 3D architecture of trabecular bone.
Characterization of a collagenous cementum-derived attachment protein
Authors: Wu Dayang , Ikezawa Kazuhiko , Parker Todd , Saito Masahiro , Narayanan A. Sampath 
Published: February 2010

Abstract
We report further characterization of a cementum-derived protein that promotes the adhesion and spreading of periodontal cells. The cementum attachment protein (CAP) was extracted from bovine cementum, separated by diethylamino ethyl (DEAE)-cellulose chromatography, and purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and C18 reverse phase high performance liquid chromatography. The purified preparation contained a single protein band migrating with Mr 56,000. It did not cross-react with polyclonal antibodies to osteopontin, vitronectin, or other attachment proteins. The attachment activity was resistant to chondroitinase ABC digestion. An internal amino acid sequence of six peptides was determined by microsequencing, and the peptide sequences were not present in other attachment proteins described in cementum. Four sequences contained Gly-X-Y repeats typical of collagen helix. One 17 amino acid peptide had 82% homology with a type XII collagen domain. However, bovine type XII collagen did not promote fibroblast attachment. Although another 19-amino-acid-long peptide had 95% homology to bovine α1[I], two other peptides were only 74% and 68% homologous, and the CAP was not recognized by anti-type I collagen antibody. The attachment activity of CAP was susceptible to bacterial collagenase. The CAP did not cross-react with antibodies to type V, XII, and XIV collagens. These data and our previous immunostaining data indicate that the CAP is not related to other collagens or attachment proteins and that it is a collagenous attachment protein localized in cementum.
Osteomalacia and osteoporosis in a woman with ankylosing spondylitis
Authors: Kohlmeier Lynn A. , Federman Micheline , Leboff Meryl S. 
Published: February 2010

Abstract
Three months postpartum, a 33-year-old woman with ankylosing spondylitis (AS) suffered multiple vertebral fractures. Bone mineral density was 61–67% of age-matched normal values at the lumbar spine and proximal femur, and an initial iliac crest bone biopsy revealed osteoporosis and osteomalacia. Secondary causes of bone disease were excluded, and the patient was treated with calcium, vitamin D, and nasal spray calcitonin (400 μ/day). Over 4 years, she has shown partial recovery of bone mass and almost complete resolution of osteomalacia. Osteoporosis and fracture occur in patients with AS, yet this case represents a rare association between AS and both osteomalacia and postpregnancy spinal osteoporosis.
A new role for the chondrocyte in fracture repair: Endochondral ossification includes direct bone formation by former chondrocytes
Authors: Miss Scammell Brigitte E. , Roach Helmtrud I. 
Published: February 2010

Abstract
We studied the endochondral ossification that occurs during the transition of soft to hard callus during fracture healing in the rabbit. During this process, parts of the cartilaginous soft callus are invaded by capillaries, and new bone is laid down onto the central unresorbed cartilage struts. We found that the chondrocytes within these cartilage struts changed phenotype and became bone-forming cells which directly replaced the central cartilage core with bone matrix. We have termed this bone “lacunar” bone to distinguish it from the “vascular” bone laid down by osteoblasts. With time the lacunar bone spread beyond the confines of the lacunae and gradually replaced all the cartilage matrix that was originally present in the early endochondral spicules. The lacunar bone could still be distinguished from the vascular bone as follows: (1) it was woven bone, whereas vascular bone was lamellar bone; (2) it contained acid phosphatase activity, whereas vascular bone did not; and (3) it had strong antigenicity for bone sialoprotein, whereas this noncollagenous protein was undetectable in vascular bone. Eventually the hard callus was resorbed and remodeled, but at an interim period of endochondral ossification the direct replacement of cartilaginous callus by the formation of lacunar bone is a rapid mechanism by which the mechanical strength of fracture callus is increased.
Relationship between body composition and bone mass in women
Authors: Khosla Sundeep , Atkinson Elizabeth J. , Riggs B. Lawrence , Melton L. Joseph 
Published: February 2010

Abstract
Increasing body weight is associated both with higher bone mass and with lower rates of bone loss. Whether the effects of body weight are mediated by lean body mass (LBM) or fat body mass (FBM) is, however, uncertain because different studies have used different measures of bone mass and arrived at contradictory conclusions. The parameter actually measured is bone mineral content (BMC). Bone mineral density (BMD), bone mineral apparent density (BMAD), and the BMD/height attempt to “correct” BMC for differences in bone or body size, but these corrections may bias the analysis of the effects of body composition on the skeleton. To resolve this issue, we measured BMC at the total body, lumbar spine, proximal femur, and forearm using dual energy X-ray absorptiometry (DXA) in a population-based sample including 138 premenopausal women (age range 21–54 years, mean 35 years) and 213 postmenopausal women (age range 34–94 years, mean 68 years). BMD, BMAD, and BMD/ height were also calculated for each site. LBM and FBM were determined from the DXA whole body scan. In a multivariate analysis that included age and height, both LBM and FBM predicted total body BMC in pre- and postmenopausal women (p &lt; 0.002 for LBM and FBM in both groups). LBM had a dominant effect on spine and forearm BMC in both groups (p &lt; 0.004) and hip BMC in premenopausal women (p &lt; 0.001), whereas both LBM and FBM predicted hip BMC in postmenopausal women (p &lt; 0.001). However, as BMC was adjusted for bone or body size using BMD, BMAD, or BMD/height, FBM tended to become more important than LBM in the analysis. This was, in part, due to the fact that each of the correction factors in the BMD and BMAD calculations, as well as height, were highly correlated with LBM (r = 0.57 and 0.52 for height versus LBM in pre- and postmenopausal women, respectively [p &lt; 0.001]), and weakly or not at all with FBM (r = 0.08 and 0.11, respectively). Therefore, dividing BMC by these correction factors tended to bias the analysis against potential effects of LBM on bone mass. Thus, the relationship between body composition and bone mass is critically dependent on which bone mass parameter is used in the analysis. Both LBM and FBM have important effects on bone mass, depending on the bone mass parameter used, the skeletal site measured, and menopausal status.
Ca2+ oscillations and intercellular Ca2+ waves in ATP-stimulated articular chondrocytes
Authors: Dr. D'Andrea R. P. , Vittur F. 
Published: February 2010

AbstractCytosolic Ca2+ oscillations are known to occur in many cell types stimulated with agonists linked to the phosphoinositide signaling pathway. Trains of repetitive short-lasting Ca2+ spikes could be induced in articular chondrocytes by extracellular ATP, an agonist potently effective in stimulating cartilage resorption. The mechanism of these Ca2+ oscillations was studied by computerized video imaging on primary cultures of articular chondrocytes. Few cycles of oscillatory activity could be evoked in the absence of extracellular Ca2+, while, for oscillations to be sustained, Ca2+ influx was required. Thapsigargin irreversibly blocked Ca2+ oscillations, thus demonstrating the crucial involvement of intracellular stores in triggering the rhythmic activity. Apart from activating intracellular Ca2+ release, extracellular ATP also induced a noncapacitive Ca2+ influx in these cells. This ATP-mediated influx modulates both the oscillation frequency and intracellular stores refilling. In monolayers of confluent cells, Ca2+ oscillations spread from cell to cell in the form of intercellular waves. Propagating waves could also be observed in the absence of extracellular Ca2+, demonstrating that Ca2+ itself is not required for signal coordination. These results demonstrate that complex spatiotemporal pathways of Ca2+ oscillations and intercellular Ca2+ waves could be activated in articular chondrocytes during degenerative diseases. (J Bone Miner Res 1996;11:946-954)
Vitamin D receptor alleles, bone mineral density and turnover in premenopausal Japanese women
Authors: Dr. Tokitan Akifumi , Matsumoto Hiroshi , Morrison Nigel A. , Tawa Toshiya , Miura Yuko , Fukamauchi Kazutaka , Mitsuhashi Naoki , Irimoto Masahiro , Yamamori Syunji , Miura Masakazu , Watanabe Takako , Kuwabara Yoshihiro , Yabuta Keijiro , Eisman John A. 
Published: February 2010

Abstract
Recent studies have shown that genetic effects on bone mineral density (BMD) and bone turnover are related to allelic variation in the vitamin D receptor (VDR) gene. We examined allelic influences of the VDR gene on bone turnover and density in 202 normal healthy premenopausal Japanese women (age 30.1 ± 1.2, mean ± SEM). The VDR effect on BMD and turnover is similar to that observed in Caucasian women; however, there are major differences in allele frequency. The B allele by Bsm I restriction fragment length polymorphisms (RFLPs), associated with low BMD and high bone turnover, is found in only 12% of Japanese women (1.4% homozygote BB), compared with 41% of Caucasians (16.7% homozygote BB). In comparing the two most frequent genotypes, Bb heterozygotes (21.5%) and bb homozygotes (77.1%), BMD is 5.3% lower in Bb heterozygotes, and levels of bone formation markers including osteocalcin and bone-specific alkaline phosphatase are 20–32% higher with lower serum calcium (2.30 ± 0.02 vs 2.35 ± 0.01 mmol/1) and higher 1,25-dihydroxyvitamin D (95 ± 4.8 vs. 76 ± 3.8 pmol/1). Further discrimination of the genotype was achieved using two additional RFLPs (Apa I, A and Taq I, T); the lumbar spine BMD of the common genotype BbAATt was 9.3% (0.94 SD) lower than in the bbaaTT genotype in premenopausal Japanese women. These data confirm that VDR RFLPs affect bone mineral metabolism regardless of racial differences. Moreover, the VDR genotypes based on haplotype analysis should yield useful insights into the potential prevention of osteoporosis. (J Bone Miner Res 1996;11:1003-1009)
A prospective study of proximal femur bone mass following cemented and uncemented hip arthroplasty
Authors: Marchetti Michael E. , Steinberg Gerald G. , Greene James M. , Jenis Louis G. , Baran Daniel T. 
Published: February 2010

Abstract
Cross-sectional studies have demonstrated significant decreases in bone mass in femoral cortical bone adjacent to prostheses. Thirty-six patients who had undergone 31 cemented and 9 uncemented primary total hip arthroplasties (THA) were prospectively studied to define further the natural history of this femoral cortical bone loss. Dual-energy X-ray absorptiometry (DXA) was employed to quantify bone mineral density (BMD) changes in four subregions around the femoral prostheses. Femoral BMD loss (average 12.3%) was observed in the three proximal subregions 2 months postoperatively. This loss increased to 21.2% by 6 months postoperatively, and by 2 years postoperatively it averaged 25.5% in the same three subregions. There were no significant BMD changes in the subregion distal to the prosthesis tip or in the contralateral hip. Subgroups were compared based on prosthesis size and cement use. Statistically significant differences in BMD loss were observed between the large cemented cobalt chrome prosthesis group (n = 8) and the large uncemented titanium prosthesis group (n = 8). These differences were only present in the most proximal medial subregion where the large cemented groups had twice the bone loss in this area as compared with the large uncemented group. The data indicate that bone loss occurs adjacent to femoral prosthesis within 2 months of surgery and that DXA is a useful technique to quantify prospectively femoral cortical bone loss following THA. (J Bone Miner Res 1996;11:1033–1039)
Evaluation in vivo of a potent parathyroid hormone antagonist: [Nle8,18, D-Trp12, Tyr34]bPTH(7–34)NH2
Authors: Dresner-Pollak Rivka , Yang Qui-Ming , Behar Vered , Nakamoto Chizu , Dr. Chorev Michael , Rosenblatt Michael 
Published: February 2010

AbstractIn an effort to design and select potent parathyroid hormone (PTH) antagonists suitable for clinical utility, a PTH analog was evaluated in vivo in an animal model to assess its properties in preparation for human studies. The previously described PTH antagonist, [Nle8,18, D-Trp12, Tyr34]bPTH(7–34)NH2, which is highly active in vitro, was documented in these studies to be an effective antagonist of the PTH-stimulated calcemic response in vivo. In thyroparathyroidectomized (TPTX) rats, the efficacy of the antagonist was demonstrated to be dose-dependent. Inhibition was demonstrated when intravenous administration of antagonist started 1 h prior to coinfusion with the PTH agonist [Nle8,18,Tyr34]bPTH(1–34)NH2. Maximal inhibition by antagonist (an 84% decline in serum calcium levels compared with agonist alone) of the calcemic response was observed when a 200-fold molar excess of antagonist (12 nmol/h) was administered. At dose ratios of antagonist:agonist as low as 10:1, a 40–50% inhibition of PTH-stimulated calcemic response is evident, provided a longer (2 h) lead time for antagonist infusion is allowed. Based on these and related studies, the antagonist [Nle8,18,D-Trp12,Tyr34]bPTH(7–34) NH2 has displayed sufficient potency to obtain approval from the appropriate institutional and regulatory agencies for clinical trials in hypercalcemic states of parathyroid and tumor origin.
Broadband ultrasound attenuation imaging: A new imaging method in osteoporosis
Authors: Roux Christian , Fournier Bruno , Laugier Pascal , Chappard Christine , Kolta Sami , Dougados Maxime , Berger Geneviève 
Published: February 2010

Abstract
The purpose of this study was to evaluate the usefulness in osteoporosis of a new ultrasound imaging device able to create a parametric image of broadband ultrasound attenuation (BUA) at the os calcis. Three regions of interest were located in the great tuberosity of the os calcis. Precision was evaluated in 37 patients. Calcaneal bone mineral density (BMD) and BUA were compared in 33 patients. In 236 patients (including 77 with osteoporotic fractures), BUA and lumbar and femoral BMD measurements were performed. The measurements were compared using correlation coefficients. Their clinical value was estimated by comparisons of the results between patients with fractures and age-matched controls, using comparisons of the means, areas under the ROC curves, and logistic regression. Precision was in a 1.4-3.3% range. Local BUA and BMD were highly correlated (r = 0.88). Significant correlations were found between BUA and lumbar (r = 0.56) and femur (r = 0.66) BMD. In multiple regression, years since menopause and weight were significant predictors of BUA. Patients with fractures had lower BUA and BMD than age-matched controls. BUA showed the largest difference between the two populations (13-16%). Areas under the ROC curves were similar for BUA and BMD. Logistic regression after adjustment for confounding factors showed that BUA discriminated between fracture and nonfracture subjects. Broadband ultrasound attenuation imaging improves the reproducibility of ultrasound measurements. It may be useful in osteoporosis, due to its good discriminating value.
The role of type I collagen in the regulation of the osteoblast phenotype
Authors: Shi Songtao , Kirk Martin , Kahn Arnold J. 
Published: February 2010

Abstract
Evidence from a variety of sources indicates that the extracellular matrix forms an important part of a feedback loop governing the migration, proliferation, and differentiation of the cells that produce it. In keeping with this, we showed previously that the extracellular matrix of a multipotential mesenchymal clonal cell line (ROB-C26) induced to differentiate into a more osteoblastic cell type by the addition of exogenous retinoic acid produces an extracellular matrix capable of osteoinductive activity in vivo and of stimulating alkaline phosphatase activity in vitro. Since type I collagen is the major structural component of this extracellular matrix, we sought to determine whether and to what extent this protein is responsible for the previously observed inductive/stimulatory activity. To this end, C26 cells are cultured on plastic, in the presence of retinoic acid, on a type I collagen film, or on an extracellular matrix from retinoic acid-treated C26 cells, and cell differentiation is assessed by measuring changes in the abundance of a number of osteoblast-related mRNAs. These determinations are made by RNAse protection assay after 3 or 6 days of incubation and include measurements of the RNAs for type I collagen, alkaline phosphatase, osteopontin, transforming growth factor α1 and β2, and Vgr-1/BMP-6. In addition, C26 cells are incubated in the presence of retinoic acid and several established inhibitors of the synthesis or assembly of extracellular matrix components and the effects on induced alkaline phosphatase activity determined. Our data show that while the collagen substrate mimics some of the effects of retinoic acid and the extracellular matrix, it cannot reproduce all of them. Specifically, while the latter two culture conditions increase the abundance of all six mRNAs, type I collagen film increases the levels of only three of the six (collagen I, alkaline phosphatase, and osteopontin). Moreover, while type I collagen film produces an increase in alkaline phosphatase message, it fails to produce a similar change in alkaline phosphatase activity, an effect seen with both retinoic acid and extracellular matrix. However, interruption of collagen I synthesis by cis-4-hydroxy-L-proline blocks the increase in alkaline phosphatase activity associated with retinoic acid treatment. Thus, it appears likely that type I collagen is a necessary but, by itself, insufficient factor to elicit the comprehensive expression of the osteoblastic phenotype in immature mesenchymal cells.