bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of extracellular calcium on insulin-like growth factor II in human bone cells
Authors: Honda Yoko , Fitzsimmons Robert J. , Baylink David J. , Mohan Subburaman 
Published: February 2010

Abstract
Extracellular calcium concentration is critically important for normal function of the body. Recently, reports have shown that cells derived from parathyroid glands contain an extracellular calcium receptor that is responsive to changes in extracellular calcium. Bone is also intimately involved in calcium homeostasis; therefore, we sought to test the hypothesis that extracellular calcium has direct effects on bone cells. Extracellular calcium was increased by the addition of varying concentrations of CaCl2 (0.4–2.0 mM) to the control medium. An increase in extracellular calcium increased cell proliferation, as assessed by 3H-thymidine incorporation, in a number of cell types including normal human bone cells derived from vertebrae (HBV155) and a number of human osteosarcoma cell lines. The increase in cell proliferation by elevated CaCl2 was dose dependent, whereas MgCl2 was not effective at the doses tested (up to 2 mM added MgCl2). To test the hypothesis that the mitogenic activity of elevated extracellular calcium involved a growth factor, levels of insulin-like growth factor II (IGF-II) were measured in the conditioned medium of HBV155 cells by radioimmunoassay after removal of binding proteins by size exclusion chromatography. The effects of an increase in extracellular calcium by 1 mM were: 1) increased culture media levels of IGF-II within 1 h of treatment, 2) the increase in IGF-II levels reached a maximum after 8 h of treatment, and 3) IGF-II levels were still elevated after 24 h of treatment. Furthermore, a blocking monoclonal antibody against IGF-II abolished the increased cell proliferation in HBV155 cells following elevation of extracellular calcium. Taken together, these findings suggest that an increase in extracellular calcium results in an increase in IGF-II which is required for the subsequent increase in cell proliferation.
Stimulatory effect of bone morphogenetic protein-2 on osteoclast-like cell formation and bone-resorbing activity
Authors: Kanatani Masanori , Sugimoto Toshitsugu , Kaji Hiroshi , Kobayashi Tatsuya , Nishiyama Katsuhito , Fukase Masaaki , Kumegawa Masayoshi , Chihara Kazuo 
Published: February 2010

Abstract
Although the action of bone morphogenetic protein (BMP) on osteoblast differentiation has been extensively investigated, its effect on osteoclast differentiation remains unknown. In the present study, in vitro effects of BMP-2 on osteoclast-like cell formation and bone resorption were examined. BMP-2 (1–100 ng/ml) significantly stimulated bone resorption by preexistent osteoclast-like cells in mouse bone cell cultures containing stromal cells, whereas it did not affect the bone-resorbing activity of isolated rabbit osteoclast-like cells. When BMP-2 was added to unfractionated bone cells after degeneration of preexistent osteoclast-like cells, BMP-2 dose-dependently stimulated osteoclast-like cell formation at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Moreover, osteoclast-like cells newly formed by BMP-2 from unfractionated bone cells possessed the ability to form pits on dentine slices. Because these results indicated that BMP-2 directly or indirectly stimulated osteoclast differentiation and activity, we next examined the direct effect of BMP-2 on osteoclast precursors in the absence of stromal cells using hemopoietic blast cells derived from spleen cells. The mRNA for BMP-2/4 receptor was detected in hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor (GM-CSF) as well as osteoblastic MC3T3-E1 cells and MC3T3-G2/PA6 stromal cells by RNase protection assay. BMP-2 dose-dependently stimulated osteoclast-like cell formation from hemopoietic blast cells supported by GM-CSF at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced 1,25(OH)2D3-induced osteoclast-like cell formation from hemopoietic blast cells. The present data are the first to indicate that BMP-2 stimulates bone resorption through both direct stimulation of osteoclast formation and activation of mature osteoclasts, possibly via stromal cells, in vitro.
Changes in phenotypic gene expression in rat mandibular condylar cartilage cells during long-term culture
Authors: Inoue Hiroyuki , Nebgen Denise , Dr. Veis Arthur 
Published: February 2010

Abstract
Gene expression patterns have been investigated in prolonged cultures of rat mandibular condylar cartilage (MCC) cells to examine the possibility of culture-induced phenotypic changes. MCC cells were isolated from newborn rats and grown in the presence of 10% fetal bovine serum (FBS) and basic fibroblast growth factor (bFGF). MCC cells were passaged and cultured in the presence of 10% FBS and bFGF until confluent. After confluence, the medium was changed to that supplemented with 10% FBS, ascorbate, and β-glycerophosphate (day 1). Mineralization and gene expression of MCC cells have been investigated. Mineralization, visualized by staining with Alizarin red, was observed to begin at day 13 in culture, and increased up to day 22 in culture, which was the length of this study. Type II collagen and aggrecan mRNAs were highly expressed at the start of culture (day 1–4) and decreased in a time-dependent manner. Type I collagen, alkaline phosphatase, and osteopontin mRNAs expressed biphasic patterns that peaked at the start of culture and the beginning of mineralization (day 13–16). Osteonectin mRNA was expressed throughout the culture period. Osteocalcin mRNA was expressed before the beginning of mineralization peaking at day 7. These observations suggest that the gene expression patterns of MCC cells can be categorized into two different periods in prolonged culture: maturation (day 1–10) and mineralization (day 13–22). The cell culture system of MCC represents a new model system in which the differentiation of embryonic MCC cells can be examined.
Early induction of alterations in cancellous and cortical bone histology after orchiectomy in mature rats
Authors: Gunness M. , Orwoll E. 
Published: February 2010

Abstract
Androgen deficiency is associated with low bone mass in humans and animals, but the remodeling alterations that lead to bone loss are unclear. Our objective was to define early responses in both cancellous and cortical bone to orchiectomy (ORX) using histomorphometry in sexually mature (4-month-old) rats. A total of 62 male rats, 4 months of age, were divided into six groups, sham operated (SH) or orchiectomized (ORX), and sacrificed 1, 2, or 4 weeks after ORX. Calcein was given 5 and 2 days before sacrifice to label mineralizing surfaces. Bone mineral density (BMD) was measured in excised femurs by dual energy X-ray absorptiometry (DEXA). Static and dynamic histomorphometry was evaluated in the cancellous bone of the proximal tibial metaphysis and lumbar vertebral bodies, and in the cortical bone of the tibial diaphysis. Osteopenia began to develop by 2 weeks after ORX, though weight gain and femur length did not change. Femoral BMD was significantly reduced and BMC decreased (NS) by 4 weeks after ORX (p &lt; 0.05). Tibial and vertebral cancellous bone volume decreased 19% and 13%, respectively, while osteoblast and osteoclast surfaces, and numbers of osteoclasts, increased after ORX. At 2 weeks post-ORX, an increase in cancellous bone formation rate was attributable primarily to an increase in mineralizing surfaces and a smaller rise in mineral apposition rate. In contrast, cortical bone periosteal, but not endosteal, bone formation rate and mineralizing surfaces decreased. We conclude that ORX stimulates cancellous and diminishes periosteal bone turnover rapidly after ORX, with subsequent decreases in bone volume and mineral density. The clear divergence in cortical and cancellous bone responses to hypogonadism raises important questions regarding the control of bone formation and its role in defining the skeletal phenotype.
Body composition and bone mineral density in premenopausal and early perimenopausal women
Authors: Salamone Loran M. , Glynn Nancy , Black Dennis , Epstein Robert S. , Palermo Lisa , Meilahn Elaine , Kuller Lewis H. , Cauley Jane A. 
Published: February 2010

Abstract
Body composition appears to be an important determinant of bone mineral density (BMD). BMD at the femoral neck, lumbar spine, and whole-body and the whole-body soft-tissue composition were measured cross-sectionally in 334 healthy premenopausal and early perimenopausal women, aged 44–50 years, using a Hologic QDR densitometer. Correlations between lean mass and BMD at the hip, spine, and whole-body were greater (r = 0.40, r = 0.44, and r = 0.45, respectively, p &lt; 0.0001) than those for fat mass (r = 0.19, r = 0.16, and r = 0.16, respectively, p &lt; 0.01). There was a significant linear trend in femoral BMD from the lowest to highest category of lean mass (0.75 ± 0.10 g/cm2, 0.80 ± 0.10 g/cm2, and 0.86 ± 0.09 g/cm2, p &lt; 0.0001). Similar trends were demonstrated for spinal and whole-body density. For categories of fat mass, there was a significant linear trend at the hip (0.78 ± 0.10 g/cm2, 0.79 ± 0.10 g/cm2, and 0.83 ± 0.10 g/cm2, p = 0.0106), but not at the spine or whole-body. There was a 5.00% (3.62, 6.38; 95% confidence limits) difference in hip BMD per unit (standard deviation) of lean mass, while only a 0.73% (-0.66, 2.11) difference in hip BMD per unit (SD) of fat mass. Differences in BMD were examined by categories of lean and fat mass (low, medium, high) for a total of nine possible combinations of lean and fat measures. BMD at the hip, spine, and whole-body were significantly higher in those with high lean mass than in those with low lean mass, irrespective of fat mass. Women with high lean/low fat had similar hip, spinal, and whole-body BMD as those with high lean/high fat, despite their significantly lower body weight (62.5 ± 3.3 kg vs 85.7 ± 5.4 kg, respectively, p &lt; 0.0001). In premenopausal and early perimenopausal women, body weight alone may not be associated with increased bone mass unless a significant proportion of that weight is comprised of lean mass. The stronger association between lean mass and BMD than that for fat mass may be attributed to differences in determinants of lean mass, such as exercise, lifestyle factors, estrogen levels, or a combination of these factors.
Hip and calcaneal bone loss increase with advancing age: Longitudinal results from the study of osteoporotic fractures
Authors: Ensrud Kristine E. , Palermo Lisa , Black Dennis M. , Cauley Jane , Jergas Michael , Orwoll Eric S. , Nevitt Michael C. , Fox Kathleen M. , Cummings Steven R. 
Published: February 2010

Abstract
It is uncertain whether or how rapidly elderly women continue to lose bone with advancing age. To determine rates of change in bone mass at the hip and at the calcaneus in elderly women and to compare these rates of change among estrogen users and nonusers, we prospectively measured rates of change in bone mineral density (BMD) at the total hip and its four subregions (mean ± SD, 3.55 ± 0.29 years between examinations) and at the calcaneus (mean ± SD, 5.69 ± 0.33 years between examinations) in 5698 community-dwelling white women aged 65 years or older at the baseline examination. The rate of decline in total hip BMD steadily increased from 2.5 mg/cm2/year (95% confidence interval 2.0 to 2.9) in women 67–69 years old to 10.4 mg/cm2/year in those aged 85 or older (95% confidence interval 8.4 to 12.4). The rate of bone loss also increased with aging at all subregions of the hip and at the calcaneus. The average loss of bone from the total hip is sufficient to increase the risk of hip fracture by 21% per 5 years in women aged 80 years or older. Compared with nonusers, current estrogen users had a 33% lower age-adjusted mean rate of loss at the total hip (2.9 vs 4.3 mg/cm2/year, p ≤ 0.0001) and a 35% lower age-adjusted mean rate of loss at the calcaneus (3.9 vs 6.0 mg/cm2/year, p ≤ 0.0001). The rate of bone loss in the hip and calcaneus steadily increases with advancing age in older women. Estrogen therapy may significantly decrease this loss. Efforts to understand and prevent bone loss should include elderly women.
Comparison of rates of bone loss from the spine measured using two manufacturers' densitometers
Authors: Peel N.F.A. , Dr. Eastell R. 
Published: February 2010

Abstract
Measurements of bone mineral density of the lumbar spine (LS-BMD) by dual-energy X-ray absorptiometry (DXA), made using different manufacturers' densitometers, differ by approximately 15%. The aim of this study was to compare the rate of bone loss from the lumbar spine measured using two manufacturers' densitometers. LS-BMD (vertebrae L2-L4) was measured using both a Lunar DPX and a Hologic QDR 1000/W in 17 postmenopausal women at baseline and 2 years. The mean rate of change of LS-BMD made using the two densitometers did not differ (DPX -0.54% per year; QDR -0.17% per year). Although rates of change of LS-BMD measured using the two densitometers correlated (r = 0.47, p = 0.05), the variance of the rates of loss differed such that, in individual subjects, the difference between the rates of loss of LS-BMD, measured using the two densitometers, was related to the average rate of loss (r = 0.61, p = 0.009). For both densitometers, as bone mineral content (BMC) increased, the measured area also increased, leading to an underestimate of change in bone mineral density (BMD). This relation differed between the two densitometers such that the change in BMD was underestimated to a greater extent by QDR. We conclude that in the context of multicenter studies it may not be possible to directly combine data on the rate of bone loss acquired using different manufacturers' densitometers.
Assessment of biochemical markers of bone metabolism in relation to the occurrence of fracture: A retrospective and prospective population-based study of women
Authors: Åkesson K. , Ljunghall S. , Jonsson B. , Sernbo I. , Johnell O. , Gärdsell P. , Obrant K.J. 
Published: February 2010

Abstract
We have in a population-based setting evaluated biochemical markers of bone metabolism in 328 women, aged 40–80 years, and related it to contents of bone mineral measurements and the retrospective and prospective presence of fracture. The participants were recruited from the city population files. Serum samples for analysis of osteocalcin (Oc), procollagen I carboxy-terminal extension peptide (PICP), and carboxy-terminal telopeptide of type I collagen (ICTP) were taken, and forearm bone mineral content (BMC) was measured by single photon absorptiometry (SPA). Fracture history was recorded, and the information was verified and supplemented from both radiologic and orthopedic files. Five years later the registration of fractures was repeated. At the initial investigation, Oc was 23% lower in women who had sustained a fracture (n = 37) within 6 years before measurement (6.3 ± 3.6 μg/1 vs 8.2 ± 4.2 μg/1 (p = 0.006)), after adjusting for age and BMC differences. PICP and ICTP were not different from values in the women without fracture. However, in women aged 70–80 years with a fracture sustained during the previous 6 years, PICP was lower (128 ± 32 μg/1 vs 144 ± 34 μg/1, p = 0.046). Oc and ICTP were significantly correlated to age and BMC (Oc-age r = 0.36, Oc-BMC r = –0.31, ICTP-age r = 0.44, ICTP-BMC r = –0.24). The correlations of PICP were weaker. Prospectively, logistic regression gave an odds ratio (OR) of 1.8 (p = 0.015) for a low PICP and fracture susceptibility, at a change of 1 SD, independent of age and BMC. In the age bracket 70–80, the odds ratio was 2.4 (p = 0.036). The odds ratio for ICTP, independent of age and BMC, was 1.9 (p = 0.043) for 1 SD decrease and subsequent fracture risk. We concluded that women who had sustained at least one recent fracture had an altered bone turnover with decreased bone formation but an unaltered resorption. Women with retrospectively registered fractures also sustained subsequent fractures. A decrease from the mean of the collagen markers PICP and ICTP was associated with an increased risk for future fracture. Utilizing these biochemical markers of bone metabolism in a female population, PICP and ICTP had a similar influence on the risk of future fracture as forearm BMC (OR = 1.6, p = 0.03).
Short-term treatment with growth hormone stimulates osteoblastic and osteoclastic activity in osteopenic postmenopausal women: A dose response study
Authors: Brixen Kim , Kassem Moustapha , Nielsen Henning K. , Loft Anne Gitte , Flyvbjerg Allan , Mosekilde Leif 
Published: February 2010

Abstract
To investigate the potential use of growth hormone (GH) in Activate-Depress-Free-Repeat treatment of postmenopausal osteoporosis, we measured changes in serum levels of biochemical markers of bone turnover, insulin-like growth factor-I (IGF-I), calciotropic hormones, and bone mineral density in 40 postmenopausal women with osteopenia (ages 52–73 years) in response to 7 days of treatment with either placebo or GH (0.05, 0.10, or 0.20 IU/kg/day) administered subcutaneously in the evening. GH treatment increased serum osteocalcin (p &lt; 0.01) and C-terminal type-I procollagen propeptide (p &lt; 0.01) and also serum levels of type-I collagen telopeptide (p &lt; 0.001), fasting urinary hydroxyproline/creatinine (p &lt; 0.05), pyridinoline/creatinine (p &lt; 0.05), and deoxypyridinoline/creatinine (p &lt; 0.01) in a dose-dependent fashion. Even the lowest dose of GH tested induced a significant increase in these parameters; however, the effects were transient lasting only 1–2 weeks. In the highest dose group, however, a somewhat prolonged effect (30 days) on serum osteocalcin was observed. Furthermore, GH increased serum levels of IGF-I, insulin, and tri-iodothyronin. No effect on serum 1,25-dihydroxyvitamin D3 or parathyroid hormone could be demonstrated. Adverse effects were mainly related to fluid retention. They were clearly dose-dependent and rapidly reversible. In conclusion, short-term GH treatment stimulates bone formation and bone resorption in postmenopausal women with osteopenia.
Radial and ulnar cortical thickness of the second metacarpal
Authors: Fox Kathleen M. , Kimura Sumiko , Powell-Threets Kia , Plato Chris C. 
Published: February 2010

Abstract
Differential bone mass at various skeletal sites, which may be due to mechanical stress exerted by the muscles attached to the bone, has been demonstrated for athletes who exert one limb more than the other. The question arises as to whether this bilateral asymmetry extends to the two sides of the same bone with different muscular attachments. The objectives of this study were to ascertain whether the radial and ulnar sides of the second metacarpal have similar cortical thicknesses and determine if bone mass decreases equally with age on the radial and ulnar sides. Hand-wrist radiographs were obtained from 201 male and 191 female Caucasian participants of the Baltimore Longitudinal Study of Aging. Differences between radial and ulnar cortical thickness within age groups were tested with Student's t-test and between age groups using analysis of variance. Radial cortical thickness of the second metacarpal was found to be 11–12% greater in men and 10–12% greater in women than ulnar cortical thickness in both the left and right hands. Age-related changes in radial cortical thickness were evident in both sexes. In men, radial cortex decreased linearly from age 40 to 89. For women, there was a sharp decline in radial thickness from age 50 to age 60. Ulnar cortical thickness declined from age 50 to 60 for women only. Muscle attachment along the radial length of the second metacarpal may influence the accumulation of bone mass on the radial side at younger ages while muscle disuse may precipitate the loss of bone preferentially from the radial side.
Soft Tissue Body Composition: Familial Resemblance and Independent Influences on Bone Mineral Density,
Authors: Krall Elizabeth A. , Dawson-Hughes Bess 
Published: February 2010

Abstract
Familial resemblance in fat and lean soft tissue and the influence of these body composition measures on bone mineral density (BMD) were determined in 162 adult members of 42 families. Whole body fat and lean mass and BMD of the spine and femoral neck were measured by dual-energy X-ray absorptiometry and BMD of the heel and radius by single-photon absorptiometry. Significant correlations of lean tissue were observed between mothers and daughters (r = 0.35, p &lt; 0.05), fathers and sons (r = 0.36, p &lt; 0.05), and daughters and sons (r = 0.42, p &lt; 0.01) after adjustment for age, height, fat mass, physical activity, and parity (among women). Fat tissue was not significantly correlated among any family member pairs. Lean tissue, but not fat, was positively associated with BMD in one or more family member subgroups at all skeletal sites. These findings suggest a hereditary component to muscle mass. Previously documented familial similarities in bone density may be related in part to the influence of lean mass on bone density.
Comparative effects of 1,25-dihydroxyvitamin D3 and EB 1089 on mouse renal and intestinal 25-hydroxyvitamin D3-24-hydroxylase
Authors: Roy Stéphane , Martel Josée , Dr. Tenenhouse Harriet S. 
Published: February 2010

Abstract
EB 1089 is a vitamin D analog that is less potent than 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in its calcemic action but more potent in its antiproliferative action. We characterized the interaction of 1,25(OH)2D3 and EB 1089 with renal 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway, and compared the effects of 1,25(OH)2D3 and EB 1089 on induction of 24-hydroxylase mRNA in mouse kidney and intestine. 1,25(OH)2D3 and EB 1089 were competitive inhibitors of 24-hydroxylase activity. However, the K1 for 1,25(OH)2D3 (5.2 ± 2.5 nM) was significantly lower than that for EB 1089 (286 ± 59 nM). In the kidney, the time course and extent of 24-hydroxylase mRNA induction, relative to 18S rRNA, was similar for 1,25(OH)2D3 and EB 1089 with a peak response at ≈ 6 h that was sustained for at least 16 h. In the intestine, however, induction of 24-hydroxylase mRNA, relative to 18S rRNA, was ∼50% lower for EB 1089 than for 1,25(OH)2D3 at 3 h (p &lt; 0.05) and 6 h (p &lt; 0.05) while at 16 h 24-hydroxylase mRNA was no longer detectable. Moreover, while both 1,25(OH)2D3 and EB 1089 elicited a similar dose-dependent induction of 24-hydroxylase mRNA in the kidney (EC50 = 0.4 ± 0.13 and 0.3 ± 0.08 ng/g for EB 1089 and 1,25(OH)2D3, respectively), the EC50 for EB 1089 (6.6 ± 1.7 ng/g) was significantly higher than that for 1,25(OH)2D3 (0.9 ± 0.32 ng/g) in the intestine (p &lt; 0.01). EB 1089 was also less effective than 1,25(OH)2D3 in the induction of intestinal but not renal calbindin-D9k mRNA. To determine the mechanism for tissue-specific differences in potency, we determined the binding affinity of 1,25(OH)2D3 and EB 1089 for the vitamin D receptor. In the kidney, Kd values for 1,25(OH)2D3 (0.40 ± 0.05 nM) and EB 1089 (0.48 ± 0.04 nM) were not different. However, in the intestine, the Kd for EB 1089 (1.43 ± 0.19 nM) was significantly higher than that for 1,25(OH)2D3 (0.85 ± 0.06 nM; p &lt; 0.05). Our results demonstrate that: (i) EB 1089 has a 50-fold lower affinity than 1,25(OH)2D3 for renal 24-hydroxylase, suggesting that it is more resistant to catabolism by the C-24 oxidation pathway; and (ii) EB 1089 and 1,25(OH)2D3 exhibit tissue-specific differences in vitamin D receptor-mediated responses in vivo that may be ascribed, at least in part, to differences in binding affinities for the vitamin D receptor.