bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Proteome Study of Secreted Prostatic Factors Affecting Osteoblastic Activity: Galectin-1 Is Involved in Differentiation of Human Bone Marrow Stromal Cells
Authors: Andersen Helle , Jensen Ole N , Moiseeva Elena P , Eriksen Erik F 
Published: April 2006

Abstract
Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found to be proteins with molecular weights between 20 and 30 kDa, but the identity of the osteoblastic mitogenic factor or factors produced by prostate cancer cells is still unknown. Therefore, the aim of this study was to characterize the protein profile of conditioned medium (CM) from PC3 cells in the molecular weight range from 5 to 30 kDa using proteome analysis. A protein profile of the CM from PC3 cells was performed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). Thirty protein spots with molecular weights ranging from 5 to 30 kDa were analyzed by matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). One of these spots was identified as galectin-1. We examined whether PC3 CM, recombinant galectin-1 alone, or combined with insulin-like growth factor-I (IGF-I) had any effects on the proliferation or differentiation of human bone marrow stromal (hBMS) cells. Furthermore, we tested whether adhesion of PC3 cells to plastic, laminin, fibronectin, and collagen type I was influenced by lactose, which inhibits galectin-1. Galectin-1 (1000 ng/ml) inhibited the proliferation of hBMS cells up to 70 ± 12% (treated/control) of control in contrast to PC3 CM, which induced hBMS cell proliferation by 3-fold. This effect was abolished by IGF-I. PC3 CM and galectin-1 in concentrations of 10 and 1000 ng/ml increased the alkaline phosphatase (ALP) activity of hBMS cells up to 175 ± 27%, 137 ± 8%, and 131 ± 11%, respectively, compared with ALP activity of untreated cells, and inhibited the secretion of osteocalcin (OC) up to 81 ± 3%, 93 ± 1%, and 58 ± 2%, respectively, compared with OC secretion of untreated cells. These effects were affected by IGF-I. Lactose inhibited adhesion of PC3 cells to plastic, fibronectin, laminin, and collagen type I up to 58 ± 4%, 30 ± 12, 72 ± 9%, and 86 ± 4%. In conclusion, galectin-1 modulated osteoblastic proliferation and differentiation. These effects were affected by IGF-I. Thus, galectin-1 is likely be involved in the osteoblastic response, caused by prostate cancer cells metastasizing into bone, by affecting the matrix mineralization.
Antagonistic Effects of Different Classes of Bisphosphonates in Osteoclasts and Macrophages In Vitro
Authors: Frith Julie C. , Rogers Michael J. 
Published: April 2006

Abstract
Nitrogen-containing bisphosphonates, such as alendronate and ibandronate, inhibit bone resorption by preventing protein prenylation in osteoclasts, whereas non-nitrogen-containing bisphosphonates, such as clodronate, are metabolized to nonhydrolyzable analogs of ATP, resulting in osteoclast apoptosis. Because these two classes of bisphosphonates have different molecular mechanisms of action, we examined in vitro whether combined treatment with clodronate and alendronate would alter antiresorptive effectiveness. Although, in cultures of rabbit osteoclasts, the antiresorptive effect of 10 μM alendronate was increased by the addition of clodronate, the effect of higher concentrations of alendronate was not altered by addition of clodronate. Furthermore, the inhibition of protein prenylation in osteoclasts caused by higher alendronate concentrations was partially prevented by cotreatment with clodronate. As in osteoclasts, the inhibition of protein prenylation in J774 cells caused by alendronate or ibandronate treatment was dose-dependently prevented by cotreatment with clodronate. Furthermore, alendronate-induced J774 apoptosis was significantly inhibited in the presence of clodronate. The presence of clodronate also decreased the short-term cellular uptake of [14C]ibandronate. These observations suggest that combined treatment with clodronate could enhance the antiresorptive effect of a low concentration of nitrogen-containing bisphosphonate, but clodronate can also antagonize some of the molecular actions and effects of higher concentrations of nitrogen-containing bisphosphonates. The exact molecular basis for the antagonistic effects between bisphosphonates remain to be determined, but could involve competition for cellular uptake by a membrane-bound transport protein.
Cathepsin K mRNA and Protein Expression in Prostate Cancer Progression
Authors: Brubaker KD , Vessella RL , True LD , Thomas R , Corey E 
Published: April 2006

Abstract
Prostate cancer (CaP) is the most commonly diagnosed malignancy in men and is often associated with bone metastases, which cause much of the morbidity associated with CaP. Lesions associated with CaP generally exhibit increased bone formation and resorption. Increased bone resorption may release factors from the extracellular matrix that contribute to tumor growth. Cathepsin K (cat K) is a cysteine protease that exhibits strong degradative activity against the extracellular matrix and is involved in osteoclast-mediated bone destruction. In this study, we analyzed the expression of cat K in CaP cell lines and patient samples. Cat K message was detected in CaP cell lines by reverse transcription-polymerase chain reaction (RT-PCR) and in primary CaP and metastases by in situ hybridization. Immunohistochemistry revealed variable expression of cat K in primary CaP samples, as well as nonosseous metastases, whereas expression in bone metastases was significantly higher than in primary CaP, and normal prostate tissues were negative. Cat K protein was detected in CaP cell lines by Western blotting after immunoprecipitation. Cat K enzymatic activity was also detected in CaP cell lines by a fluorogenic assay and by an assay for degradation of collagen type I. Increased levels of NTx, a marker of bone matrix degradation mediated primarily by cat K, were also detected in sera of patients with CaP bone metastases. We hypothesize that CaP-expressed cat K may contribute to the invasive potential of CaP, while increased expression in bone metastases is consistent with a role in matrix degradation.
Endoglin Is Expressed on Human Chondrocytes and Forms a Heteromeric Complex With Betaglycan in a Ligand and Type II TGFβ Receptor Independent Manner
Authors: Parker Wendy L , Goldring Mary B , Philip Anie 
Published: April 2006

Abstract
Previous work has implicated transforming growth factor β (TGFβ) as an essential mediator of cartilage repair and TGFβ signaling as a requirement for the maintenance of articular cartilage in vivo. However, the mechanisms regulating TGFβ action in chondrocytes are poorly understood. Endoglin, an accessory receptor of the TGFβ receptor superfamily, is highly expressed on endothelial cells and has been shown to potently modulate TGFβ responses. It is not known whether chondrocytes express endoglin or whether it modulates TGFβ signaling in these cells. In this study, we show that endoglin is expressed on human chondrocytes at levels comparable with endothelial cells and that it forms higher order complexes with the types I and II TGFβ receptors. More importantly, we show that endoglin forms a heteromeric complex with betaglycan on these cells at endogenous receptor concentrations and ratios. Endoglin complexes with betaglycan in a ligand-independent and -dependent manner as indicated by co-immunoprecipitation in the absence of TGFβ and after affinity labeling with radiolabeled TGFβ, respectively. Also, the endoglin-betaglycan association can occur independently of the type II TGFβ receptor. These findings, taken together with the available evidence that endoglin and betaglycan are potent modulators of TGFβ signal transduction, imply that the complex formation between endoglin and betaglycan may be of critical significance in the regulation of TGFβ signaling in chondrocytes.
Relative Contributions of Bone Density, Bone Turnover, and Clinical Risk Factors to Long-Term Fracture Prediction
Authors: Melton L Joseph , Crowson Cynthia S , O'Fallon W Michael , Wahner Heinz W , Riggs B Lawrence 
Published: April 2006

Abstract
Long-term fracture prediction using bone mineral density remains controversial, as does the additional contribution from assessing bone turnover or clinical risk factors. We measured bone mineral density at various sites, along with biochemical markers of bone turnover, sex steroid levels, and over 100 clinical variables, at baseline on an age-stratified sample of 304 Rochester, MN women in 1980. The 225 postmenopausal women were subsequently followed for 3146 person-years (median, 16.2 years per subject), wherein they experienced 302 new fractures: 81% resulted from minimal or moderate trauma and 60% of these involved the proximal femur, thoracic or lumbar vertebrae, or distal forearm. Accounting for multiple fractures per subject, these osteoporotic fractures together were best predicted by baseline femoral neck bone mineral density (age-adjusted hazard ratio [HR] per SD decrease, 1.37; 95% CI, 1.10–1.70); 19 moderate trauma forearm fractures were best predicted by distal radius bone mineral content, whereas 28 hip fractures and 100 vertebral fractures were best predicted by femoral neck bone mineral density. Femoral neck bone mineral density performed comparably in predicting osteoporotic fracture risk within the first decade of follow-up (HR, 1.38; 95% CI, 1.10–1.74) as well as more than 10 years after baseline (HR, 1.39; 95% CI, 1.05–1.84). The older biochemical markers were not associated with fractures, but serum “free” estradiol index was independently predictive of short- and long-term fracture risk. Consistent clinical risk factors were not identified, but statistical power was limited. Identifying patients at increased long-term risk of fracture is challenging, but it is reassuring that femoral neck bone mineral density can predict osteoporotic fractures up to 20 years later.
Ten-Year Longitudinal Relationship Between Physical Activity and Lumbar Bone Mass in (Young) Adults
Authors: Bakker Ingrid , Twisk Jos WR , Van Mechelen Willem , Roos Jan C , Kemper Han CG 
Published: April 2006

Abstract
Little is known about the influence of long-term daily physical activity (PA) on lumbar bone mass after peak bone mass has been reached, that is, during [young] adulthood. The purpose of this study was to investigate the longitudinal relationship between PA and lumbar bone mineral density (LBMD) in healthy subjects over a 10-year period. The data reported here relate to 225 male and 241 female participants in the Amsterdam Growth and Health Longitudinal Study, who were measured at the mean ages of 27, 32, and/or 36. LBMD, habitual daily PA, total body weight, and calcium intake were assessed at each measurement point. The effects of two aspects of PA were analyzed: the mechanical (MECHPA; sum of all ground reaction forces) and metabolic (METPA; weighted metabolic score of intensity, frequency, and duration) components, each within a separate model. Multilevel analysis was used to investigate the relationship between PA and LBMD over the 10-year period. Gender, total body weight, and calcium intake were included in the analysis as covariates. The results indicated that MECHPA was a significant positive linear predictor of LBMD for males (r = 0.09; p &lt; 0.001) but not for females. For the METPA, no linear longitudinal relationship with LBMD was found. The results suggest that there is a metabolic threshold at which extra PA becomes “deleterious” and METPA in its totality becomes ineffective for LBMD. It is concluded that during the (young) adult period, between 27 and 36 years of age, PA causing mechanical loading on the skeleton has a small positive influence on LBMD in males.
Hormone Replacement Therapy Dissociates Fat Mass and Bone Mass, and Tends to Reduce Weight Gain in Early Postmenopausal Women: A Randomized Controlled 5-Year Clinical Trial of the Danish Osteoporosis Prevention Study
Authors: Jensen LB , Vestergaard P , Hermann AP , Gram J , Eiken P , Abrahamsen B , Brot C , Kolthoff N , Sørensen OH , Beck-Nielsen H , Nielsen S Pors , Charles P , Mosekilde L 
Published: April 2006

Abstract
The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45–58 years from 3 months to 2 years past last menstrual bleeding were included. One thousand were randomly assigned to HRT or no HRT in an open trial, whereas the others were allocated according to their preferences. All were followed for 5 years for body weight, bone mass, and body composition measurements. Body weight increased less over the 5 years in women randomized to HRT (1.94 ± 4.86 kg) than in women randomized to no HRT (2.57 ± 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias.
Distinct Anabolic Response of Osteoblast to Low-Intensity Pulsed Ultrasound
Authors: Naruse Kouji , Miyauchi Akimitsu , Itoman Moritoshi , Mikuni-Takagaki Yuko 
Published: April 2006

Abstract
Low-intensity pulsed ultrasound, a form of mechanical energy transmitted as high-frequency acoustical pressure waves, provides noninvasive therapeutic treatment for accelerating fracture repair and distraction osteogenesis. Relatively young osteoblasts respond to ultrasound by transiently upregulating message levels of immediate-early genes as well as that of osteocalcin and insulin-like growth factor I (IGF-I). Osteocytes derived from newborn rat tibia and calvaria responded to a lesser extent only in c-fos and cyclooxygenase-2 (COX-2) messages. Compared with the stretched osteocytes, which use stretch-activated and parathyroid hormone (PTH)-potentiated Ca2+ influx as an entry route to the protein kinase A (PKA) signal transduction pathways, there was no evidence of Ca2+ internalization by any of the cells tested on exposure to the ultrasound. On the other hand, inhibitors of p38 mitogen-activated protein kinase (MAPK) and upstream phosphoinositide 3-kinase (PI3K) blocked COX-2 and osteocalcin upregulation by the ultrasound-exposed ST2, murine bone marrow-derived cells. This is distinct from the aforementioned osteocytic response to low-frequency stretching and implies the involvement of integrins. Our findings suggested that accelerated fracture repair and distraction osteogenesis by the low-intensity pulsed ultrasound depend, at least in part, on the stimulation of osteoblastic cells at relatively early stages of osteogenic lineage. Bone is under control of multiple regulatory mechanisms so that diverse physical forces can be reflected to the microenvironment of each cell, in turn, to the entire bone.
Bone Loss Detection in Rats Using a Mouse Densitometer
Authors: Binkley N , Dahl DB , Engelke J , Kawahara-Baccus T , Krueger D , Colman RJ 
Published: April 2006

Abstract
Estrogen-depletion bone-loss studies often use ovariectomized (ovx) rats and measure bone mineral density in vivo or ex vivo using DXA. Recently, a portable densitometer (PIXImus) was developed for mouse research; however, its use in rats is unclear. This study compared the ability of PIXImus and a standard densitometer (DPXL) to detect ovx-induced bone loss in rats both in vivo and ex vivo. Additionally, instrument accuracy was assessed by comparing measured bone mass with ash weight. Finally, the use of two distal femur regions of interest (ROI) to detect ovx-induced bone loss was evaluated. Twenty-three 6-month-old nulliparous female Sprague-Dawley rats were randomly assigned to sham or ovx groups. Distal femur bone mineral density was assessed at baseline and at 1 and 2 months postoperatively, using a PIXImus and DPXL densitometer. At 3 months postoperatively, all animals were killed, and ex vivo femur scans obtained. Distal femur bone loss was demonstrable by 1 month post-ovx using either densitometer. With the PIXImus, a 4-mm ROI demonstrated greater bone loss (p &lt; 0.05) than an 8-mm ROI. Using the 4-mm ROI, similar amounts of bone loss were detected by the PIXImus and DPXL: 22.2% and 22.4%, respectively, at 2 months post-ovx. Total femur bone mineral content was overestimated by the PIXImus but highly correlated with the DPXL measurement (r = 0.988) and ash weight (r = 0.998). Given its comparability to standard DXA plus its rapid scan speed and portability, the PIXImus is useful in evaluating ovx-induced osteopenia in rats.
Growth Hormone Increases Bone Mineral Content in Postmenopausal Osteoporosis: A Randomized Placebo-Controlled Trial
Authors: Landin-Wilhelmsen Kerstin , Nilsson Anders , Bosaeus Ingvar , Bengtsson Bengt-Åke 
Published: April 2006

Abstract
Eighty osteoporotic, postmenopausal women, 50–70 years of age, with ongoing estrogen therapy (HRT), were randomized to recombinant human growth hormone (GH), 1.0 U or 2.5 U/day, subcutaneous, versus placebo. This study was double-blinded and lasted for 18 months. The placebo group then stopped the injections, but both GH groups continued for a total of 3 years with GH and followed for 5 years. Calcium (750 mg) and vitamin D (400 U) were given to all patients. Bone mineral density and bone mineral content were measured with DXA. At 18 months, when the double-blind phase was terminated, total body bone mineral content was highest in the GH 2.5 U group (p = 0.04 vs. placebo). At 3 years, when GH was discontinued, total body and femoral neck bone mineral content had increased in both GH-treated groups (NS between groups). At 4-year follow-up, total body and lumbar spine bone mineral content increased 5% and 14%, respectively, for GH 2.5 U (p = 0.01 and p = 0.0006 vs. placebo). Femoral neck bone mineral density increased 5% and bone mineral content 13% for GH 2.5 U (p = 0.01 vs. GH 1.0 U). At 5-year follow-up, no differences in bone mineral density or bone mineral content were seen between groups. Bone markers showed increased turnover. Three fractures occurred in the GH 1.0 U group. No subjects dropped out. Side effects were rare. In conclusion, bone mineral content increased to 14% with GH treatment on top of HRT and calcium/vitamin D in postmenopausal women with osteoporosis. There seems to be a delayed, extended, and dose-dependent effect of GH on bone. Thus, GH could be used as an anabolic agent in osteoporosis.
Association of a Haplotype (196Phe/532Ser) in the Interleukin-1-Receptor-Associated Kinase (IRAK1) Gene With Low Radial Bone Mineral Density in Two Independent Populations
Authors: Ishida Ryota , Emi Mitsuru , Ezura Yoichi , Iwasaki Hironori , Yoshida Hideyo , Suzuki Takao , Hosoi Takayuki , Inoue Satoshi , Shiraki Masataka , Ito Hiromoto , Orimo Hajime 
Published: April 2006

Abstract
Osteoporosis, a multifactorial common disease, is believed to result from the interplay of multiple environmental and genetic determinants, including factors that regulate bone mineral density. Interleukin-1 (IL-1) is one of the most potent bone-resorbing factors, and interleukin-1-associated kinase 1 (IRAK1) is an essential effector of the IL-1 receptor signaling cascade. In genetic studies of two independent populations of postmenopausal women (cohort A: 220 individuals and cohort T: 126 individuals) from separated geographical regions of Japan, we found that radial bone mineral density levels had similar associations with IRAK1 genotypes in both populations. Two amino acid-substituting variations in the gene, encoding Phe196Ser and Ser532Leu, were in complete linkage disequilibrium (D′ = 1.0000, r2 = 1.0000, χ2 = 192.000, p = 1.2 × 10−43), and we found two exclusive haplotypes (196F/532S, frequency 0.74; 196S/532L, frequency 0.26) of the IRAK1 gene among our test subjects. In both populations, a significant association with decreased radial bone mineral density was identified with haplotype 196F/532S (in cohort A: r = 0.21, p = 0.0017; in cohort T: r = 0.23, p = 0.011). Radial bone mineral density was lowest among 196F/532S homozygotes, highest among 196S/532L homozygotes, and intermediate among heterozygotes. Accelerated bone loss also correlated with the 196F/532S haplotype in a 5-year follow-up. These results suggest that variation of IRAK1 may be an important determinant of postmenopausal osteoporosis, in part through the mechanism of accelerated postmenopausal bone loss.
Abnormal Regulation of Renal 25-Hydroxyvitamin D-1α-Hydroxylase Activity in X-Linked Hypophosphatemia: A Translational or Post-Translational Defect
Authors: Fujiwara Ikuma , Aravindan Rolands , Horst Ron L , Drezner Marc K 
Published: April 2006

Abstract
The hyp mouse exhibits abnormal metabolic/hormonal regulation of renal 25(OH)D-1α-hydroxylase activity. Whether this results from aberrant transcriptional regulation of the 1α-hydroxylase gene, CYP27B1, remains unknown. To investigate this possibility, we compared phosphate and parathyroid hormone effects on renal proximal convoluted tubule and thyrocalcitonin effects on proximal straight tubule enzyme activity and mRNA expression in normal and hyp mice. We assayed 25(OH)D-1α-hydroxylase activity by measuring 1,25(OH)2D production and mRNA by ribonuclease protection. Phosphate-depleted mice exhibited a 3-fold increment of 25(OH)D-1α-hydroxylase activity compared with normals, whereas hyp mice displayed no enhanced enzyme function. Phosphate-depleted mice concurrently displayed a 2-fold increase in mRNA transcripts; in contrast, despite failure to alter enzyme activity, hyp mice exhibited a similar increment in mRNA transcripts. Parathyroid hormone stimulation of normal mice increased 25(OH)D-1α-hydroxylase activity 10-fold, while eliciting only a 2-fold increment in hyp mouse enzyme function. This disparity occurred despite increments of mRNA transcripts to comparable levels (22.2 ± 3.5- vs. 19.9 ± 1.8-fold). The dissociation between phosphate- and parathyroid hormone-mediated transcriptional activity and protein function was not universal. Thus, thyrocalcitonin stimulation of normal and hyp mice resulted in comparable enhancement of mRNA transcripts and enzyme activity. These observations indicate that abnormal regulation of vitamin D metabolism in hyp mice occurs in the proximal convoluted tubule and results, not from aberrant transcriptional regulation, but from a defect in translational or post-translational activity.