bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine production and surface antigen expression by peripheral blood mononuclear cells in postmenopausal osteoporosis
Authors: Hustmyer Frank G. , Walker Edwin , Yu Xiao-Peng , Girasole Giuseppe , Sakagami Yoshiyuki , Peacock Munro , Manolagas Stavros C. 
Published: February 2010

Abstract
It was reported earlier that IL-1 production by cultured monocytes and the ratio of helper (CD4) to suppressor (CD8) lymphocytes in peripheral blood are different in osteoporotic compared to nonosteoporotic subjects. We examined these and several other parameters related to the biosynthetic activity and differentiation status of peripheral blood mononuclear cells (PBMC) in untreated osteoporotic postmenopausal women (age 65 ± 7, n = 46), nonosteoporotic postmenopausal women (age 55 ± 3, n = 20), and nonosteoporotic premenopausal women (age 37 ± 7, n = 8), as defined by spine density. We found that unstimulated monocytes from osteoporotics did not produce detectable IL-1β as determined by ELISA. In addition, there were no significant differences between osteoporotics and nonosteoporotics in IL-1β or IFN-γ production by PBMC stimulated with OKT3, a monoclonal antibody to the T cell-receptor complex. The proliferative response of lymphocytes to OKT3 was significantly less (p &lt; 0.02) in osteoporotics compared to nonosteoporotic post- and premenopausal women; multiple-regression analysis, however, indicated that this difference was not due to bone density but to age. Flow cytometric analysis of PBMC revealed no difference between osteoporotics and nonosteoporotics in the distribution of 18 phenotypic subsets determined, including CD4-or CD8-positive lymphocytes or the ratio of CD4 to CD8 cells. Further, there was no correlation of the surface markers with bone density, the exceptions being the subsets expressing the CD3/CD56 and CD8/CD56 markers, which were inversely related to spine density in the osteoporotic women. Nonetheless, in the osteoporotic women, the CD8/CD56 and CD14/CD13 cells were positively correlated with the levels of plasma 1,25-(OH)2D3 (r = 0.33, p &lt; 0.04; r = 0.39, p = 0.028, respectively), whereas the CD4 cells were negatively correlated with 1,25-(OH)2D3 (r = −0.35, p = 0.026). These data suggest that cytokine production by peripheral blood mononuclear cells and the distribution of the various subsets of these cells in the peripheral blood are not related to bone mass in osteoporosis. Distribution of PBMC subsets in the peripheral blood, however, may be influenced by circulating levels of 1,25-(OH)2D3.
Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels
Authors: Guidon Peter T. , Salvatori Roberto , Bockman Richard S. 
Published: February 2010

AbstractGallium nitrate, a group IIIa metal salt, has been found to be clinically effective for the treatment of accelerated bone resorption in cancer-related hypercalcemia and Paget's disease. Here we report the effects of gallium nitrate on osteocalcin mRNA and protein levels on the rat osteoblast-like cell line ROS 17/2.8. Gallium nitrate reduced both constitutive and vitamin D3-stimulated osteocalcin protein levels in culture medium by one-half and osteocalcin mRNA levels to one-third to one-tenth of control. Gallium nitrate also inhibited vitamin D3 stimulation of osteocalcin and osteopontin mRNA levels but did not affect constitutive osteopontin mRNA levels. Among several different metals examined, gallium was unique in its ability to reduce osteocalcin mRNA levels without decreasing levels of other mRNAs synthesized by ROS 17/2.8 cells. The effects of gallium nitrate on osteocalcin mRNA and protein synthesis mimic those seen when ROS 17/2.8 cells are exposed to transforming growth factor β1 (TGFβ1); however, TGF-β1 was not detected in gallium nitratetreated ROS 17/2.8 cell media. Use of the RNA polymerase II inhibitor 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole demonstrated that gallium nitrate did not alter the stability of osteocalcin mRNA. Transient transfection assays using the rat osteocalcin promoter linked to the bacterial reporter gene chloramphenicol acetyltransferase indicated that gallium nitrate blocked reporter gene expression stimulated by the osteocalcin promoter. This is the first reported effect of gallium nitrate on isolated osteoblast cells.
Serum markers of type I collagen formation and degradation in metabolic bone disease: Correlation with bone histomorphometry
Authors: Eriksen Erik F. , Charles Peder , Melsen Flemming , Mosekilde Leif , Risteli Leila , Risteli Juha 
Published: February 2010

Abstract
Type I collagen makes up more than 90% of bone matrix. Therefore, analysis of antigens related to collagen formation and degradation in bone should provide good and specific estimates of both bone resorption and bone formation rates. In this study we measured serum levels of the pyridinoline cross-linked telopeptide domain of type I collagen (ICTP) as a marker of bone resorption and serum carboxy-terminal propeptide of type I procollagen (PICP) as a marker of bone formation. Serum levels of the two antigens were correlated to histomorphometric indices of bone resorption and bone formation calculated from iliac crest bone biopsies in a group of 18 individuals with high- and low-turnover bone disease (myxedema, primary hyperparathyroidism, and thyrotoxicosis). After logarithmic transformation the regression of S-ICTP on volume-referent resorption rate (BRs/R/BV) was significant (r = 0.61, p &lt; 0.01, SEM/Y = 56%). S-ICTP also showed a significant regression on the volume-referent cancellous bone balance (r = −0.45, p &lt; 0.05, SEM/Y = 412%).
S-PICP was significantly correlated to the mineral appositional rate (r = 0.53, p &lt; 0.05) and volume-referent bone formation rate (r = 0.61, p &lt; 0.01, SEM/Y = 48%). The correlation to bone turnover as expressed in the activation frequency was also highly significant (r = 0.61, p &lt; 0.01, SEM/Y = 51%). No significant correlation with wall thickness or bone balance was demonstrable per remodeling cycle. Thus, assays employing antigens that reflect collagen formation and degradation are useful instruments for the evaluation of rates of bone remodeling in metabolic bone disease.
Autocrine regulators of MC3T3-E1 cell proliferation
Authors: Amarnani Saral , Merriman Harold L. , Linkhart Thomas A. , Baylink David J. , Mohan Subburaman 
Published: February 2010

Abstract
MC3T3-E1 cells, a clonal osteoblast-like mouse calvarial cell line, secrete several growth regulating factors. These regulators include insulin-like growth factor (IGF) type I, transforming growth factor β (TGF-β), and IGF-II in descending order of abundance. MC3T3-E1 cells in culture also produce two IGF binding proteins (IGFBP), Mr 25 and 32 kD, having sequence identity with IGFBP-4 and IGFBP-6, respectively. In addition, this is the first observation that osteoblast-like bone cells in culture produce IGFBP-6. To determine if growth factors produced by MC3T3-E1 cells have autocrine actions on these cells, the effects of IGF-I, IGF II, TGF-β1, and IGFBP-4 on MC3T3-E1 cell proliferation were determined. Exogenous addition of IGF-I and IGF-II stimulated MC3T3-E1 cell proliferation, but TGF-β1, and IGFBP-4 inhibited MC3T3-E1 cell proliferation. Based on these findings, we conclude that MC3T3-E1 cells in culture produce autocrine regulators of MC3T3-E1 cell proliferation and that the actions of IGFs may also be regulated by IGFBPs produced by these same cells.
Pre- and postmenopausal bone mineral density of the spine and proximal femur in Japanese women assessed by dual-energy X-ray absorptiometry: A cross-sectional study
Authors: Soda Masa-Yuki , Mizunuma Hideki , Honjo Shige-Ichirou , Okano Hiroya , Ibuki Yoshito , Igarashi Masao 
Published: February 2010

Abstract
To investigate the influence of menopause on bone mineral density (BMD) of Japanese women, BMD of the spine and proximal femur was measured by dual-energy x-ray absorptiometry (DXA) in 220 premenopausal and 166 postmenopausal Japanese women. The peak bone density of the spine in premenopausal women was detected between 35 and 39 years of age, and that of femur before 20. Thereafter spinal and femoral BMD showed a slight decrease, but they did not show a significant decrease until menopause or menstruation became irregular. Duration of substantial bone loss at lumbar spine continued for about 10 years after menopause, but that at the femur was much longer. To investigate the effect of early menopause on bone loss, postmenopausal women were divided into two groups according to the age at onset of menopause. The BMD of postmenopausal women whose menopause occurred before 50 was significantly less over the latter part of life than that of women whose menopause occurred after 50. These results suggest that bone loss is related to menopause or irregular menstruation rather than age per se, and early menopause should be recognized as one of the risk factors for involutional osteoporosis.
Leukemia inhibitory factor inhibits osteoclastic resorption, growth, mineralization, and alkaline phosphatase activity in fetal mouse metacarpal bones in culture
Authors: Van Beek Ermond , Van Der Wee-Pals Lianne , Van De Ruit Marjan , Nijweide Peter , Papapoulos Socrates , Löwik Clemens 
Published: February 2010

Abstract
Leukemia inhibitory factor (LIF) has been reported to affect bone metabolism, but results are variable. We examined the effect of mouse recombinant LIF on osteoclastic resorption in fetal bone explants representing different stages of osteoclast development. In cultures of 17-day-old fetal mouse metacarpals in which only osteoclast progenitors and precursors are present, resorption (measured as 45Ca release) was significantly inhibited to 29.2% and to 96.6% in the presence of LIF 100 and 1000 U/ml, respectively. Histologic examination of the explants treated with 1000 U/ml of LIF confirmed the biochemical findings and showed that osteoclast progenitors and precursors remained in the periosteum and did not invade the mineralized matrix. In metacarpals of older fetuses (18- and 19-day-old) in which the mineralizied cartilage has been invaded by mature osteoclasts, the inhibition of resorption by LIF (1000 U/ml) was 87.9 and 74.7%, respectively, the latter being significantly less than the inhibition observed in 17-day-old metacarpal cultures. The inhibitory effect of LIF was absent during concurrent administration of PTH or 1,25-(OH)2D3 and could be reversed by PTH. In addition, LIF was found to inhibit growth, mineralization, and alkaline phosphatase activity in metacarpals independently of osteoclastic resorption. These results suggest that LIF affects the development rather than the activity of osteoclasts, probably through an effect on the osteogenic cells. LIF may be an important endogenous regulator of bone metabolism.
Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis
Authors: Storm Tommy , Steiniche Torben , Thamsborg Gorm , Melsen Fleming 
Published: February 2010

Abstract
Intermittent, cyclic etidronate therapy (400 mg/day for 2 weeks followed by 13 weeks free from study drug administration) resulted in a significant increase in lumbar bone mineral content and a significant decrease in the rate of new vertebral fractures in patients with postmenopausal osteoporosis. To investigate the effect of the treatment on bone histomorphometry, transiliac crest bone biopsy samples were obtained in this study before treatment and after 60 and 150 weeks of treatment with either intermittent, cyclic etidronate (n = 33) or placebo (n = 33). After 60 weeks of etidronate therapy, significant decreases in activation frequency (from 0.55 to 0.09 year,−1P &lt; 0.01) and resorption depth (from 53.2 to 37.8 μm, P &lt; 0.05) were observed, leading to a positive balance per remodeling cycle. In the placebo group, no significant changes were seen. The 150 week bone biopsy samples were suboptimal for analysis, probably as a result of a regional acceleratory phenomenon. Our results suggest that, as a result of reductions in both activation frequency and resorption depth, intermittent, cyclic etidronate therapy may protect the trabecular network against fortuitous perforations and thereby maintain the strength of the bony tissue.
Role of bone matrix in osteoclast recruitment in cultured fetal rat calvariae
Authors: Braidman Isobel P. , Anderson David C. 
Published: February 2010

Abstract
In cultured 19 day fetal rat calvaria, osteoclasts first appear after 48 h, more rapidly than with other cultured embryonic long bone rudiments. This may be because the calvarial osteoclast precursors are more differentiated or intramembraneous bone is a more powerful stimulus for osteoclast maturation than endochondral bone. To investigate this further, 19 day calvariae were stripped of their endocranial membranes, devoiding them of osteoclast precursors, and cocultured with the membranes or with other sources of these cells, such as bone marrow, fetal liver, spleen, and blood. There was similar recruitment of mature osteoclasts onto the surface of the “stripped” calvariae from the endocranial membranes and from the hematopoietic tissues after 48 h culture. Intact 19 day fetal calvariae were cultured with human recombinant granulocyte-macrophage colony-stimulating factor (hrGM-CSF) or with 1,25-dihydroxyvitamin D3, [1,25-(OH)2D3], each thought to influence different stages of osteoclast maturation. They stimulated osteoclast recruitment, although 1,25-(OH)2D3 was effective only in the first 24 h of culture. They also increased osteoclast recruitment from fetal liver onto stripped calvariae. When intact bones were cultured with hrGM-CSF and 1,25-(OH)2D3 together, osteoclast number decreased but their area increased. Calvariae therefore appear to contain osteoclast precursors at earlier (GM-CSF-sensitive) and later [1,25-(OH)2D3-sensitive] stages. As recruitment onto stripped calvariae was similar whichever source of precursors was used, it is likely that calvarial bone matrix is an important influence on rapid osteoclast maturation in these bones in vitro.
Attachment to extracellular matrix molecules by cells differing in the expression of osteoblastic traits
Authors: Majeska Robert J. , Port Michael , Einhorn Thomas A. 
Published: February 2010

Abstract
Two sets of clonal cell populations differing in the expression of osteoblastic traits, the rat osteosarcoma cell lines ROS 17/2.8 and ROS 25/1 and the immortalized fetal rat calvarial cell lines RCT-1 and RCT-3, were compared for their ability to attach to a series of extracellular matrix (ECM) constituents in vitro. Both osteoblastic (ROS 17/2.8, RCT-3) and nonosteoblastic (ROS 25/1, RCT-1) cell lines attached in a time- and concentration-dependent manner to plates coated with fibronectin (FN), osteopontin (OP), type I collagen (Col I), type IV collagen (Col IV), and laminin (LN) but only weakly to osteocalcin (OC) and thrombospondin (TSP). In both systems, the osteoblastic and nonosteoblastic clones attached identically to FN. Both ROS 17/2.8 and ROS 25/1 attached to similar molar amounts of substrate with the same preference order: FN &gt; LN &gt; Col I ≥ Col IV. Maximal ROS 17/2.8 attachment to OP was ≥ Col I but required approximately 2.5 times more substrate. ROS 25/1 attached less effectively than ROS 17/2.8 to most non-FN substrates. RCT-3 cells attached similarly to ROS 17/2.8 except that the preference order for Col I and LN was reversed and attachment to OP was lower than for ROS 17/2.8 RCT-1 cells attached best to Col I rather than FN, and equaled or surpassed RCT-3 in attachment to other non-FN substrates. Thus in these experimental systems, cells expressing an osteoblast-like phenotype exhibited generally similar ECM attachment properties. Their nonosteoblastic counterparts recognized the same spectrum of ECM constituents but differed from the osteoblastic cells and from each other in the effectiveness of their attachment to substrates other than FN.
Pattern of gene expression following rat tibial marrow ablation
Authors: Suva Larry J. , Seedor Gregory J. , Endo Naoto , Quartuccio Helen A. , Thompson David D. , Bab Itai , Rodan Gideon A. 
Published: February 2010

Abstract
Following injury to bone marrow there is a phase of osteogenesis in which bone trabeculae replace the initial blood clot and fill the marrow cavity. The newly formed bone is subsequently fully resorbed by osteoclasts and normal bone marrow is restored. In this study we correlated the morphologic events with the pattern of gene expression that defines this sequence. Following marrow ablation, the trabecular bone volume in the affected section of the marrow cavity increased from control to 27% at day 6, declined to 18% at day 8, and eventually returned to control levels at day 14. Osteoblast number increased up to day 6 and declined substantially by day 8, but the number of osteoclasts peaked between days 8 and 10. Histologic analysis of alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP) activity correlated with the observed cellular changes. Northern blot analysis of the levels of AP, osteocalcin (OC), and osteopontin (OP) mRNA shows a specific pattern of regulated gene expression, with AP mRNA maximal at day 6, OC mRNA very low until days 6–8, and OP mRNA expressed at very high levels throughout. In addition, procollagen α1(I) and α1(III) mRNAs show a regulated pattern of expression, with procollagen α1(I) maximally expressed between days 4 and 10 and procollagen α1(III) expressed at lower levels between days 4 and 6. The mRNA encoding insulin-like growth factor I (IGF-I) was found to be highly expressed between days 5 and 12; however, transforming growth factor β1, (TGF-β1) and TGF-β3 mRNA were only weakly expressed between days 4 and 10. These data demonstrate a temporal pattern of gene expression consistent with the observed morphologic profile, identify changes in growth factor mRNA that may be related to this repair process, and suggest that this is a suitable model for studying in vivo a synchronized sequence of bone formation and resorption at a well-defined anatomic site.
Protein kinase C-activating domains of parathyroid hormone-related protein
Authors: Dr. Gagnon Lyne , Jouishomme Hervé , Whitfield James F. , Durkin Jon P. , MacLean Susanne , Neugebauer Witold , Willick Gordon , Rixon Ray H. , Chakravarthy Balu 
Published: February 2010

Abstract
N-terminal fragments of PTH-related protein (PTHrP), PTHrP-(1–34), and PTHrP-(1–40) stimulated both adenylyl cyclase and a mechanism that increases membrane-associated protein kinase C (PKC) activity in ROS 17/2 rat osteosarcoma cells. There were two peaks in the PKC response to the N-terminal PTHrP fragments: one peak was obtained with picomolar and the other with nanomolar PTHrP concentrations. The PKC-stimulating picomolar concentrations of the PTHrP fragments did not detectably stimulate adenylyl cyclase, but the nanomolar concentrations did. Since a similar two-peak response of PKC activity was obtained with PTHrP-(28–34), the single, N-terminal PKC activation domain of the PTHrP is in the same 28–34 region of the molecule as that of PTH despite this region having different primary amino acid sequences in the two hormones. Unlike PTH, PTHrP has a second PKC activation domain, as indicated by the ability of picomolar concentrations of the PTHrP-(107–111) fragment to stimulate maximally membrane-associated PKC activity in the osteosarcoma cells.
Outcome of bone mineral density in anorexia nervosa patients 11.7 years after first admission
Authors: Herzog Wolfgang , Minne Helmut , Deter Christian , Leidig Gudrun , Schellberg Dieter , Wüster Christian , Gronwald Rainer , Sarembe Egbert , Kröger Friedebert , Bergmann Günther , Petzold Ernst , Hahn Peter , Schepank Heinz , Ziegler Reinhard 
Published: February 2010

Abstract
Osteopenia is a typical finding in patients suffering from anorexia nervosa. Unfortunately, available longitudinal studies are limited by a relatively short follow-up period. Therefore cross-sectional long-term follow-up studies may help to determine both the outcome of this bone lesion and variables that influence its subsequent development. Of an initial 66 consecutive patients with anorexia nervosa, 51 (77.3%) could be further evaluated. After an average of 11.7 years following first admission, cross-sectional measurements of lumbar and proximal radial bone mineral density (BMD) were performed. The ability to predict BMD using variables obtained from anamnestic and clinical data was then determined by multiple-regression analysis. The BMD of both radial and lumbar bone in anorexic patients with poor disease outcome (as defined by the Morgan-Russell general outcome categories) deviated by −2.18 and −1.73 SD (Z score), respectively. In patients with a good disease outcome lumbar BMD was significantly less reduced compared with radial BMD (–0.26 versus −0.68 SD). Variables reflecting estrogen deficiency and nutritional status in the course of the disease, that is, relative estrogen exposure (for lumbar BMD) and years of anorexia nervosa (for radial BMD), allowed the best prediction of BMD. A marked reduction in cortical and trabecular BMD in anorexic patients with poor disease outcome suggests a higher risk of fractures in these patients. Furthermore, the finding of a persistently reduced cortical and a slightly reduced trabecular BMD, even in patients with good disease outcome, suggests that a recovery of trabecular BMD might be possible, at least in part. Recovery of cortical bone, if possible at all, seems to proceed more slowly.
Procollagen synthesis and extracellular matrix deposition in MG-63 osteosarcoma cells
Authors: Jukkola Arja , Risteli Leila , Melkko Jukka , Dr. Risteli Juha 
Published: February 2010

Abstract
We compared the procollagen synthetic properties of MG-63 osteosarcoma cells with those of cultured human skin fibroblasts. In both cells, the expressions of type I and III procollagens are largely dependent on the constant presence of ascorbate and coordinately decreased by the neutral polymer dextran T-40. The amino-terminal propeptides of pro-α1 and pro-α2 chains of type I procollagen are phosphorylated and those of the pro-α1 and pN-α1 chains of type III procollagen both phosphorylated and sulfated, there being no difference in net charge in the propeptides between these cell types. The major differences between MG-63 and normal fibroblasts are the exceptionally high relative synthesis of type III procollagen by MG-63 cells, up to about 40% of the total of types I and III (6% in cultured skin fibroblasts), and the inability of ascorbate-supplemented MG-63 cells to deposit collagens into an insoluble pericellular matrix. A longer dextran treatment shifts up to one-fourth of the proline-labeled extracellular macromolecules into the matrix fraction within 4 days (in control 4%). Despite processing of the procollagens to the respective collagens in the matrix, neither control matrices nor those induced by dextran induced increased production of alkaline phosphatase. In cultures up to 4 days postconfluence the proportion of type III collagen produced tended to increase over that in early confluent cultures. With respect to collagen production, the MG-63 cell line is not a representative of the osteoblast lineage but rather resembles a proliferative wound fibroblast.