bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone-resorbing activity of thyroid hormones is related to prostaglandin production in cultured neonatal mouse calvaria
Authors: Klaushofer Klaus , Hoffmann Oskar , Gleispach Helmut , Leis Hans-Jörg , Czerwenka Erwin , Koller Kristian , Peterlik Meinrad 
Published: February 2010

Abstract
The bone-resorbing activity of thyroid hormones was evaluated in neonatal mouse calvaria maintained in organ culture for 96 h. Thyroxine (T4) between 10−8 and 10−5 mol/liter and triiodothyronine (T3) between 10−8 and 10−7 mol/liter caused a dose-dependent release of calcium from cultured bone. The thyroid hormone effect was delayed in onset for at least 24 h, and after 96 h of culture amounted to 50–90% of the bone-resorbing activity of 10−8 mol/liter parathyroid hormone (PTH). The bone-resorbing action of T4 as well as of T3 was completely blocked by 100 U/ml interferon-γ (IF-γ) or 20 mU/ml salmon calcitonin (CT). “Escape” from CT inhibition, which is a well-known phenomenon in the action of PTH, was not observed with thyroid hormone-mediated bone resorption. Thyroid hormone treatment of cultured calvaria resulted in a gradual increase between 48 and 96 h of medium concentrations of prostaglandin (PG) E2 and particularly of 6-keto-PGF1α, the inactive metabolite of prostacyclin (PGI2). The release of PGF2α in general was not significantly affected. Although the effect of thyroid hormones on PG release from cultured calvaria was completely abolished by 5 × 10−7 mol/liter indomethacin, in some experiments indomethacin reduced thyroid hormone-mediated bone resorption by only 50%. This indicates that thyroid hormone action on bone is also mediated by a PG-independent mechanism.
Comparison of cross-sectional and longitudinal measurements of age-related changes in bone mineral content
Authors: Davis James W. , Ross Philip D. , Wasnich Richard D. , Maclean Charles J. , Vogel John M. 
Published: February 2010

Abstract
Age-related, postmenopausal bone loss was examined among a cohort of Japanese-American women living in Hawaii. None of the women were using estrogens or thiazides. Cross-sectional and longitudinal measurements of bone mineral content were compared at the calcaneus, the proximal radius, and the distal radius. Cross-sectional measurements were also available for the lumbar spine. The longitudinal data showed a slowing rate of bone loss with increasing age at the radius sites. By contrast, the cross-sectional data suggested constant rates of bone loss for all ages at both radius sites and the spine. The calcaneus demonstrated a complex pattern of bone loss in both cross-sectional and longitudinal analyses. The loss rates among women in their fifties were greater than for those in their sixties. From the middle sixties onward calcaneal bone loss remained essentially constant. Because of the sustained bone loss, however, women in their seventies were actually losing greater percentages of their calcaneal bone mineral than they had in their sixties.
Accelerated bone resorption in senescence-accelerated mouse (SAM-P/6)
Authors: Kawase Masahiro , Tsuda Masao , Matsuo Takao 
Published: February 2010

Abstract
Age-associated changes in the femoral bone and in urine and serum composition were studied to understand the low bone mass in a substrain of senescence-accelerated mouse (SAM), SAM-P/6. Age-matched normal SAM-R/1 mice were used as controls. After 13 weeks of age, the concentration of hydroxyproline in the femur of SAM-P/6 was slightly but significantly lower. The urinary excretion rates of cAMP and calcium were higher in SAM-P/6 throughout the whole experimental period, and those of hydroxyproline and phosphorus were higher after 8 weeks. The serum concentrations of calcium and inorganic phosphorus of SAM-P/6 were higher at 13 and 20 weeks. At 5 weeks, the serum alkaline phosphatase and tartrate-resistant acid phosphatase (TRAP) activities of SAM-P/6 were significantly higher. Furthermore, the serum of SAM-P/6 significantly stimulated calcium release from cultured fetal rat ulna. Since urinary cAMP and TRAP in the serum reflect the circulating level of parathyroid hormone and osteoclastic function, respectively, the present results suggest that, in SAM-P/6, accelerated bone resorption produced by a putative hyperparathyroid state causes the decrease in bone mass.
Renal cell carcinoma in tissue culture secretes nondialyzable product that stimulates bone resorption in organ-cultured mouse calvaria
Authors: Dr. Lerner Ulf H. , Ljungberg Börje 
Published: February 2010

Abstract
The bone-resorbing capacity of human renal cell carcinomas in vitro has been examined. Bone resorption in cultures of mouse calvarial bones was assessed by the release of 45Ca from bones prelabeled in vivo and the mobilization of stable calcium and inorganic phosphate from nonlabeled bones. In addition, bone organic matrix degradation was determined either by the release of 3H from [3H]proline-labeled bones or by the loss of hydroxyproline from bone explants during culture. Tumor tissue-conditioned media (TCM) from 13 of 13 renal cell carcinomas stimulated bone resorption in a dose-dependent manner. From 5 of 13 kidneys with renal cell carcinoma, normal kidney cortex tissue was cultured and 4 of these 5 also produced bone-resorbing activity, but the amount was much less compared with the tumor tissue. The stimulatory effect of TCM on 45Ca release could be observed first after 12–24 h of culture. The effect could be inhibited by calcitonin but not by inhibitors of prostaglandin synthesis. The production of bone-resorbing activity by tumor cells could be inhibited by indomethacin and meclofenamic acid. In some tumors, the inhibition by indomethacin was total, whereas in other tumors only partial inhibition could be obtained. In 3 of 4, TCM bone-resorbing activity could be found in the retentate after dialysis. The results show that fresh human renal cell carcinoma tissue can elaborate prostanoid as well as nonprostanoid products that can stimulate bone resorption.
Acetate inhibition of chick bone cell proliferation and bone growth in vitro
Authors: Saitta Joseph C. , Lipkin Edward W. , Howard Guy A. 
Published: February 2010

Abstract
A hypothesis has been advanced that parenteral solutions as commonly formulated for use in clinical practice have a toxic effect on cell metabolism. A specific component of these solutions, sodium acetate, has been suggested to disrupt normal bone turnover and therefore to contribute to the osteopenia observed in patients receiving hemodialysis and parenteral nutrition (PN). We developed an in vitro model to test the hypothesis that sodium acetate at concentrations that are infused in PN solutions has a deleterious effect on bone metabolism. Osteoblasts and preosteoblasts from 16- to 17-day-old embryonic chick calvaria, and tibiae and femora from 10-day-old embryonic chicks were grown in BGJb medium (control) or in BGJb medium plus sodium acetate (5, 10, or 20 mM). Calvarial cell proliferation was quantified by direct cell counts as well as by incorporation of [3H]TdR into DNA as an index of cell proliferation. Calvarial cell alkaline phosphatase activity was quantified by the ability of extracts of the cultured cells to hydrolyze p-nitrophenyl phosphate to p-nitrophenol, and bone growth was determined by measuring final dry weight. Calvarial cell counts as well as DNA synthesis showed a dose-dependent decrease in the presence of sodium acetate (5–20 mM) compared with controls. [3H]TdR incorporation was decreased a mean 19% with 5 mM, 38% with 10 mM, and 63% with 20 mM acetate. Alkaline phosphatase activity per cell increased 48% with 5 mM, 140% with 10 mM, and 355% with 20 mM acetate. Cell viability as assessed by trypan blue exclusion was identical for test and control media (&gt;95%). Long bone dry weight was decreased 6% with 5 mM acetate, 15% with 10 mM, and 33% with 20 mM acetate compared with controls. These effects were independent of the presence or absence of fetal bovine serum in the culture medium and could not be accounted for by pH differences between the test and control media. We conclude that sodium acetate inhibits the proliferation of chick osteoblasts and preosteoblasts as well as the growth of chick long bones in vitro and that the potential role of sodium acetate in parenteral solutions as a contributor to abnormal bone metabolism merits further investigation.
Cyclosporin A in the oophorectomized rat: Unexpected severe bone resorption
Authors: Movsowitz Colin , Epstein Sol , Ismail Firhaad , Fallon Michael , Thomas Steven 
Published: February 2010

Abstract
Local factors, such as interleukin-1, may mediate the accelerated bone remodeling in the acute estrogen-deficient rat. Cyclosporin A (CsA), which in vitro inhibits some of these local factors, was administered to oophorectomized (OX) rats in an attempt ot modify this high turnover state. Three groups of 15 rats were studied. Group A was sham operated, group B was OX, and group C was OX and received CsA (15 mg/kg per day) by gavage commencing 4 days postoophorectomy for 28 days. Estradiol levels were determined to confirm oophorectomy. Blood was sampled on days −7, 0, 7, 14, 21, and 28 for ionized calcium (Ca2+), 1,25-(OH)2-vitamin D, PTH, and bone gla protein (BGP). Rats received tetracycline hydrochloride for bone histomorphometric labeling. All results were compared to group A. Body weight was increased in group B (p &lt; 0.003) but not in group C. There was no difference in Ca2+ or PTH between the groups. BGP levels were higher in group B by day 28 (p &lt; 0.05); BGP levels were increased in group C from days 7–28 (p &lt; 0.002). 1,25-(OH)2-vitamin D was significantly increased in group C (p &lt; 0.0001) but not in group B. Tibial bone histomorphometry revealed increased measurements of bone formation and osteoclast number without a loss of bone volume (BV/TV) in group B. Group C showed a dramatic increase in bone turnover with significant loss of BV/TV (p &lt; 0.001). In conclusion, CsA in the OX rat resulted in unexpected enhanced bone remodeling with high BGP levels and severe bone resorption. These changes may be due to CsA alone or may be modified by oophorectomy.
Relationship of body composition, muscle strength, and aerobic capacity to bone mineral density in older men and women
Authors: Bevier Wendy C. , Wiswell Robert A. , Pyka Gisela , Kozak Kathryn C. , Newhall Katherine M. , Marcus Robert 
Published: February 2010

Abstract
We evaluated the relationship of body composition, maximal aerobic capacity (VO2max), and muscle strength to bone mineral density in 91 healthy men and women, age 61–84 years. Lean body mass was estimated from two independent measures of fat mass, bioelectrical impedance and skinfold thickness. VO2max was determined by treadmill ergometry with direct measurement of oxygen consumption. Grip and back strength were measured by isometric dynamometry. Mineral density of lumbar spine and midradius were measured by dual- and single-photon absorptiometry. Men had significantly greater lean mass, muscle strength, aerobic capacity, and bone density than women. In women, grip strength correlated with forearm and spine density (r = 0.37, r = 0.28, p &lt; 0.05). In men, grip strength correlated with forearm density (r = 0.47, p &lt; 0.05), and back strength was significantly correlated with both spine (r = 0.46, p &lt; 0.01) and forearm density (r = 0.46, p &lt; 0.01). In women, neither forearm nor spine density correlated significantly with aerobic capacity. In men, midradius density did not correlate significantly with oxygen consumption, but the simple correlation between spine density and VO2max was significant (r = 0.41, p &lt; 0.05). Back strength and VO2max were significantly related in men (r = 0.47, p &lt; 0.01). By stepwise multiple regression, back strength emerged as the most robust predictor of spine mineral, accounting for 19% of the variation in bone density. Addition of VO2max to the regression did not add significant predictive value. However, when VO2max was expressed per kilogram lean body mass, both back strength and VO2max contributed significantly to the prediction of spine density in men, and the coefficient of determination R2 increased to 0.30. We conclude that body mass and grip strength, but not aerobic capacity, significantly predict bone density in elderly women. In elderly men, back strength is a more robust predictor of axial bone density than traditional expressions of aerobic capacity, but VO2max per kilogram lean mass and back strength both make significant contributions to the prediction of spine mineral density. The applicability of these results to younger men and women is uncertain.
Calcium absorption in women: Relationships to Calcium intake, Estrogen status, and age
Authors: Heaney Robert P. , Recker Robert R. , Stegman Mary Ruth , Moy Alan J. 
Published: February 2010

Abstract
A total of 526 absorption studies, using both the double-isotope and balance-based methods, were performed in 189 middle-aged women in good general health. The study extended over 17 years of observation, with most subjects studied from two to four times at 5 year intervals. Each study was done on the woman's own self-selected calcium intake and was carried out under inpatient, metabolic balance controls.
There was a highly significant inverse correlation between calcium intake and absorption fraction, with the best fit provided by an hyperbola in which absorption fraction is approximately inversely proportional to the square root of intake. The range of absorptive performance was very broad at all intake levels. Mean absorption fraction declined from a value of 0.45 at very low intakes (approximately 200 mg Ca per day) to approximately 0.15 at intakes above 2000 mg/day. There was a highly significant fall in absorption efficiency with age, amounting to approximately 0.0021 per year and a one-time decrease, amounting to approximately 0.022 at the time of menopausal estrogen loss.
The effects of fluoride on bone and implant histomorphometry in growing rats
Authors: Turner Russell T. , Francis Rita , Hannon Kathleen S. , Brown Daniel , Garand Joseph , Bell Norman H. 
Published: February 2010

Abstract
The effects of fluoride at concentrations of 2.0 and 4.5 mM in drinking water on growth rate, vitamin D, water and mineral metabolism, bone histomorphometry, and osteoinduction of demineralized allogenic bone matrix (DABM) were compared in the rat. Whereas fluoride did not influence fluid intake or growth rate at the lower concentration, it increased fluid intake and inhibited growth rate at the higher concentration. Fluoride produced dose-related increases in serum fluoride and alkaline phosphatase but did not alter serum 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D. Serum calcium and phosphate were reduced by fluoride at concentrations of 2.0 mM but not 4.5 mM. Cancellous bone fractional area was increased by fluoride at 2.0 mM and was reduced by fluoride at 4.5 mM. Fluoride had no effect on cancellous bone surface length or the percentage surface lined by osteoblasts and osteoclasts. Fluoride increased medullary area and decreased the endosteal bone formation rate. Fluoride increased periosteal bone formation and apposition rates at concentrations of 2.0 mM but not 4.5 mM. Fluoride inhibited mineralization in DABM implants, and at the higher concentration, fluoride increased the formation of new bone matrix. These results indicate that in the rat, fluoride increases cortical and trabecular bone at therapeutic doses and reduces trabecular bone at toxic doses. The serum concentration of flouride at therapeutic doses in the rat is similar to that in patients with osteoporosis who are on treatment with fluoride. In the rat, there is a narrow range between toxic and therapeutic doses.
Parathyroid hormone-induced ornithine decarboxylase activity in fetal rat osteoblasts
Authors: Dr. van Leeuwen J.P.T.M. , Bos M. P. , Herrmann-Erlee M.P.M. 
Published: February 2010

Abstract
Induction of ornithine decarboxylase (ODC, E.C. 4.1.1.17) activity by parathyroid hormone (PTH) in cultured fetal rat osteoblasts was studied. PTH induced ODC activity and stimulated cAMP production in a dose-dependent manner, the ED50 for cAMP being five times as high as that for ODC. Induction of ODC activity by PTH was partly inhibited by actinomycin D and cycloheximide, with 40 and 55% inhibition, respectively. PTH increased the intracellular ionized calcium concentration ([Ca2+]1), which was absent in a Ca2+-free medium. Blocking calcium influx, lowering the extracellular calcium concentration, and adding trifluoperazine inhibited both induction of ODC activity and stimulation of cAMP production by PTH. A23187 (100 nM and 1 μM), combined with a low dose of PTH (4 nM), resulted in a synergistic induction of ODC activity and an inhibition of cAMP production. A23187 inhibited induction of ODC activity as well as stimulation of cAMP production by the dose of PTH (20 nM) maximally effective in inducing ODC activity. Forskolin together with this maximal dose of PTH resulted in an additive effect on ODC activity and a synergistic stimulation of cAMP production. The current results show similarities and differences with respect to results obtained with osteoblasts from other species and osteoblast cell lines. The present data indicate that (1) PTH stimulates ODC activity and this is partly due to new enzyme synthesis; (2) calcium is involved in induction of ODC activity and stimulation of cAMP production by PTH; furthermore, it is suggestive that calmodulin and/or protein kinase C are involved; and (3) stimulation of cAMP production by PTH depends on an optimal intracellular calcium concentration range.
Hypercalcemia fails to suppress elevated serum parathyroid hormone concentrations during lactation in rats
Authors: Garner Sanford C. , Boass Agna , Dr. Toverud Svein U. 
Published: February 2010

Abstract
We have previously reported that increased serum immunoreactive parathyroid hormone (iPTH) in the lactating (L) rat is generally accompanied by hypocalcemia when diets containing 0.4% calcium (Ca) or less are fed. However, instances were also observed in which elevated iPTH levels did not coincide with a hypocalcemia signal. To test the hypothesis that iPTH levels can remain elevated even in the presence of hypercalcemia in lactation, a diet containing 1.2% Ca and 0.4% phosphorus (P) was fed to lactating rats in three experiments (A, B, and C) to achieve serum ionized calcium (ICa) levels approximately 10% above levels for nonmated (NM) controls. The serum ICa of NM controls fed the 1.2% Ca diet was slightly, but significantly, elevated, and serum iPTH (determined by an N-terminal specific assay) was significantly suppressed compared with NM controls fed a 0.4% Ca diet. In experiment A, L rats fed a 1.2% Ca diet had 81% higher serum iPTH levels than NM controls fed the same diet in spite of a mean (+SEM) ICa level of 1.77 + 0.05 mM for L rats versus 1.46 + 0.01 mM for NM controls; NM controls fed a 0.4% Ca diet had serum ICa of 1.37 + 0.01 mM. This novel finding of significantly higher iPTH and ICa in L compared with NM rats fed a 1.2% Ca and 0.4% P diet was confirmed in experiment B with eight rats in each group of L or NM rats fed either the 1.2% or the 0.4% Ca diet. In experiment C, Ca IP (3 mg per 100 g body weight), which raised the serum ICa level of 20 day L rats fed 1.2% Ca diet to 2.20 + 0.18 mM at 40 minutes postinjection, did not suppress the elevated serum iPTH level (14.5 + 1.2 pg/ml for L versus 11.3 + 0.6 for NM). In NM rats fed the 0.4% Ca diet, however, Ca IP caused a rise in serum ICa to 1.86 + 0.04 mM and suppressed serum iPTH from 11.9 + 0.7 to 9.5 + 0.4 pg/ml (p &lt; 0.02) at 40 minutes. In experiment D injected iPTH-(1–34) disappeared from the circulation of L rats at a rate not significantly different from that in NM rats. It is suggested that during lactation PTH secretagogues other than hypocalcemia can stimulate PTH secretion so that even supraphysiological serum Ca levels do not suppress PTH secretion to the same degree as in NM rats.
Cyclooxygenase inhibitors enhance cell growth in an osteoblastic cell line, MC3T3-E1
Authors: Fujimori Akira , Tsutsumi Masaharu , Fukase Masaaki , Fujita Takuo 
Published: February 2010

Abstract
To elucidate the significance of endogenous prostaglandin E2 (PGE2) in osteoblastic cell function, we studied the effects of cyclooxygenase inhibitors on cell growth and alkaline phosphatase (ALP) activity in MC3T3-E1 cells. UMR-106 cells were also used as references in our experiments. MC3T3-E1 cells, cultured in α-minimal essential medium containing 10% fetal bovine serum, were shown to produce PGE2, which was markedly suppressed in the presence of indomethacin. Addition of indomethacin resulted in an increase in DNA content and [3H]thymidine incorporation. A similar growth stimulatory effect was observed when structurally different cyclooxygenase inhibitors, that is, acetyl salicylic acid (ASA), flurbiprofen, and piroxicam, were added. These cyclooxygenase inhibitors, however, differed in their effects on ALP activity. Indomethacin and ASA enhanced ALP activity, whereas flurbiprofen and piroxicam suppressed it. We then examined the effects of exogenous addition of PGE2. Although exogenous PGE2 at 6 × 10−6 M slightly stimulated cell growth, it inhibited cell growth at 6 × 10−8 M and 6 × 10−7 M. ALP activity was reduced in a dose-dependent fashion by exogenous PGE2. These results suggest that PGE2 produced by MC3T3-E1 may be suppressing cell proliferation and that cyclooxygenase inhibitors, per se, may stimulate cell growth by inhibiting endogenous PGE2 production in MC3T3-E1 cells. UMR-106 cells also produced PGE2, although less than MC3T3-E1 cells. In UMR-106 cells, the cyclooxygenase inhibitors did not influence DNA content or ALP activity as distinctly as in MC3T3-E1 cells. DNA content in these cells was reduced only by a high concentration of exogenous PGE2 (6 × 10−6 M), and ALP activity was unaltered by exogenous PGE2. Thus, although endogenous prostaglandins had a growth inhibitory effect on UMR-106 cells similar to those on MC3T3-E1 cells, its role may be less important in UMR-106 cells.
Effects of transforming growth factor α and interleukin-1 on DNA synthesis, collagen synthesis, procollagen mRNA levels, and prostaglandin E2 production in cultured fetal rat calvaria
Authors: Dr. Hurley Marja M. , Fall Pamela , Harrison John R. , Petersen Donna N. , Kream Barbara E. , Raisz Lawrence G. 
Published: February 2010

Abstract
Transforming growth factor α (TGF-α) and interleukin-1 (IL-1) have been shown to affect bone metabolism in vitro by prostaglandin-dependent and PG-independent mechanisms. We assessed the effects of the combination of these two agents on [3H]thymidine (TdR) incorporation into DNA, DNA content, [3H]proline incorporation into collagenase-digestible (CDP), noncollagen protein (NCP), and PGE2 production in 21 day fetal rat calvaria cultured for 24–96 h. We also determined whether TGF-α plus IL-1 altered procollagen mRNA levels at 96 h. TGF-α, 1–30 ng/ml, produced a 41–59% increase in TdR incorporation into DNA, but the effect was partially blocked by human recombinant IL-1. At 96 h TGF-α alone or in combination with IL-1 significantly increased the DNA content of calvaria. At 96 h, TGF-α inhibited CDP labeling and the addition of IL-1 further enhanced this inhibitory effect. The enhanced inhibitory effect of TGF-α plus IL-1 on collagen synthesis was associated with a synergistic increase in prostaglandin accumulation in the medium. Addition of indomethacin blocked PGE2 accumulation and partially reversed the inhibitory effect of TGF-α alone or in combination with IL-1 on collagen synthesis. TGF-α decreased procollagen mRNA levels by 55%, but the combination of TGF-α plus IL-1 decreased procollagen mRNA levels by 82%. Our results show that TGF-α and IL-1, which are both produced by certain tumors as well as activated macrophages, appear to act synergistically to increase prostaglandin synthesis and inhibit collagen synthesis in vitro. Thus these agents may have a regulatory role on bone formation in vivo.