bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of collagen type I and biglycan mRNA levels by hormones and growth factors in normal and immortalized osteoblastic cell lines
Authors: Thiébaud D. , Guenther H.L. , Porret A. , Burckhardt P. , Fleisch H. , Hofstetter W. 
Published: February 2010

Abstract
Growth factors, such as transforming growth factor β (TGF-β) and insulin-like growth factors (IGF) I and II, have been shown to exert anabolic effects on bone cells in vitro. Hormones, such as PTH and probably insulin and growth hormone, were recently shown to stimulate bone formation in vivo as well. The aim of the present study was to assess by northern blots, which were quantitated by densitometry, the effects of these anabolic growth factors and hormones in two osteogenic cell populations: CRP 10/30 cells, a clonal cell population derived from primary rat calvarial cells, and IRC 10/30-myc cells, which were established from CRP 10/30 by immortalization. Transcripts for α1(I) collagen, biglycan, osteonectin, osteopontin, and osteocalcin were detected in both cell populations, which is consistent with the phenotype expressed by mature osteoblasts. There were no difference in the basal expression of bone matrix mRNAs between the two cell populations. PTH increased α1(I) collagen mRNA levels in both osteoblastic cells but had no effect on the biglycan transcripts. Neither insulin nor growth hormone affected mRNA levels of either matrix protein after 24 h exposure. All three growth factors, TGF-β, IGF-I, and IGF-II, increased α1(I) collagen transcripts in a time- and dose-dependent manner in both cell populations. Biglycan mRNA levels were enhanced in both osteoblastic lines only by IGF-I and IGF-II, but not TGF-β. The transcriptional effect was ascertained by nuclear run-on assays or actinomycin inhibition. When the effects of TGF-β, IGF-I, and IGF-II on the expression of α1(I) collagen and biglycan mRNAs were compared in the two cell populations, there was a similar pattern of response. The only significant difference between the immortalized cell line and the parent cell population was a stronger stimulation of α1(I) collagen mRNA by TGF-β and a delayed increase in biglycan mRNA levels in IRC 10/30-myc. The results show that the immortalized cell line IRC 10/30-myc is useful to study the modulation of two osteoblastic markers, α1(I) collagen and biglycan mRNA, in response to exogenous factors. Biglycan is little modulated and only by IGFs, whereas PTH, IGF-I and II, and TGF-β strongly increase α1(I) collagen transcripts, confirming their anabolic effects on bone cells in vitro.
Normal osteoclastic and osteoblastic responses to exogenous growth hormone in patients with postmenopausal spinal osteoporosis
Authors: Kassem M. , DR. Brixen K. , Blum W.F. , Mosekilde L. , Eriksen E.F. 
Published: February 2010

Abstract
The cause of bone loss in patients with osteoporosis is not known, but both increased bone resorption and decreased bone formation have been reported. Theoretically, these effects may result from either increased activity of osteoclasts or decreased activity of osteoblasts, or both. In vivo, growth hormone (GH) administration leads to activation of osteoclasts and osteoblasts as evidenced by increased biochemical markers of bone resorption and bone formation. To test for disturbances in responsiveness of bone cells to exogenous hormonal stimuli in osteoporosis, we compared 15 patients with postmenopausal osteoporosis with 15 healthy age-matched postmenopausal women before and during a 3 day stimulation test with GH (0.2 IU/kg/day). Serum insulin-like growth factor I increased in both groups (p &lt; 0.001). GH treatment increased biochemical markers of bone resorption (serum carboxyl-terminal telopeptide of type I collagen [ICTP] [p &lt; 0.001] and, to a lesser extent, 24 h urinary hydroxyproline/creatinine) in the two groups. Similarly, biochemical markers for bone formation increased in both groups [osteocalcin (p &lt; 0.01) and procollagen type I C-terminal propeptide, PICP (p &lt; 0.001)]. GH treatment reduced alkaline phosphatase (ALP, p &lt; 0.05) and its bone-specific isoenzyme (bone ALP, p &lt; 0.01) in both groups. The maximal response, the area under the curve (AUC) of response curves for IGF-I, bone resorption markers, and bone formation markers were not different between groups. Our data do not support the hypothesis that osteoporotic patients display major disturbances in responsiveness to GH.
Single-cell analysis of cyclic AMP response to parathyroid hormone in osteoblastic cells
Authors: Civitelli Roberto , Bacskai Brian J. , Mahaut-Smith Martyn P. , Adams Stephen R. , Avioli Louis V. , Tsien Roger Y. 
Published: February 2010

Abstract
We previously demonstrated that the [Ca2+], response to PTH is heterogeneous in single UMR-106-01 osteogenic sarcoma cells. To verify whether response heterogeneity is a universal feature of PTH signal transduction, cAMP production was monitored in monolayer cultures of UMR-106-01 cells and human trabecular bone osteoblasts (HOB) using the cAMP-sensitive fluorescent indicator FICRhR. FICRhR was microinjected into single cells, and the 500-530/&gt;560 nm fluorescence ratio was monitored by confocal laserscanning video imaging as a measure of cAMP concentration ([cAMP]). Virtually all UMR-106-01 cells exposed to bovine PTH(1-34) (10−7 M) exhibited an increase in intracellular [cAMP], with an average fluorescence ratio change of 145 + 17% of baseline (n = 15), corresponding to nearly maximal dissociation of protein kinase A. In the continued presence of the hormone (10−7 M), [cAMP] remained elevated for at least 30 minutes. This effect was accompanied by a slow translocation of the fluorescein-labeled catalytic subunit of protein kinase A from the cytoplasm to the nucleus. In contrast, PTH(1-34) caused no detectable increase in [cAMP] in HOB cells, although PGE2 (3 x 10−6 M) stimulation was able to increase the FICRhR ratio (154 + 27%, n = 10). The truncated fragment PTH (2-34) was only 67% as potent at PTH(1-34), but deletion of the first two amino acids at the N terminus abolished the hormone's ability to stimulate cAMP production in UMR-106-01 cells. Brief exposure to 10−7 M of either PTH(3-34) or PTH(7-34) did not affect the amplitude of the fluorescence ratio change induced by equimolar doses of PTH(1-34). Thus, in osteoblast-like cells stimulated with PTH, the [cAMP] response is much more homogeneous from cell to cell than the [Ca2+]i response.
Correlates of bone mineral density in the postmenopausal estrogen/progestin interventions trial
Authors: Marcus Robert , Greendale Gail , Blunt Barbara A. , Bush Trudy L. , Sherman Sherry , Sherwin Roger , Wahner Heinz , Wells Bradley 
Published: February 2010

Abstract
We assessed the cross-sectional relationship of age, menopausal years, body mass, previous estrogen use, and ethnic background to bone mineral status in a sample of 875 healthy postmenopausal women at the time they were recruited from the community to participate in a multicenter clinical trial. The women were 1-10 years postmenopause, 45-64 years of age, and had not received estrogen replacement therapy within 3 months of enrollment. Of the participants, 89% were white, 69% had a spontaneous menopause, and 53% had a history of previous estrogen replacement therapy. Bone mineral density (BMD) of the lumbar spine (L2-4) and proximal femur was measured by dual-energy x-ray absorptiometry. Results were consistent with a significant negative linear regression of BMD on age or years from menopause. Body mass index (BMI) correlated significantly with BMD at all sites (L 2-4 r = 0.28; femoral neck r = 0.34, p &lt; 0.0001). BMD adjusted for age and BMI were higher at both sites in women who had taken estrogen versus those who had not (L2-4 0.976 + 0.009 versus 0.932 + 0.01; femoral neck 0.740 + 0.006 versus 0.708 + 0.008, p &lt; 0.05). Adjusted BMD also increased with duration of ERT. Parity was negatively associated with L2-4 BMD (p = 0.03) but did not correlate significantly with BMD at the femoral neck. Black women had the highest L2-4 BMD, and Hispanic women had the highest femoral neck BMD, even when results were adjusted for age and BMI. When data were corrected for differences in bone size, these interethnic differences were no longer significant. We conclude that increased body mass is positively correlated with BMD, and this may confer a degree of skeletal protection to heavier postmenopausal women. Exposure for 5 years to exogenous estrogen is associated with significantly increased age- and BMI-adjusted BMD.
The bone-remodeling transient: Implications for the interpretation of clinical studies of bone mass change
Authors: Heaney Robert P. 
Published: February 2010

AbstractA computer simulation of the bone-remodeling transient is described, in which the focus is explicitly on changes in clinically measurable bone mass (or density). Based upon quantitative remodeling data accumulated by histomorphometry and calcium tracer kinetics, the simulation shows that much of the apparent gain in bone produced by several agents currently employed to treat osteoporosis can be explained as a remodeling transient rather than as a fundamental alteration of remodeling balance. Even gains as large as 30% or more can be produced by nothing more than the remodeling transient under certain plausible combinations of basal remodeling rate, remodeling period, and degree of bone loss. The simulation further highlights the importance, in evaluating bone-active agents, of separating the response across the first remodeling period from bone changes that may ensue thereafter.
Low bone mass in idiopathic renal stone formers: Magnitude and significance
Authors: Jaeger Philippe , Lippuner Kurt , Casez Jean-Paul , Hess Bernhard , Ackermann Daniel , Hug Christian 
Published: February 2010

Abstract
To assess bone mineral density (BMD) in idiopathic calcium nephrolithiasis, dual-energy x-ray absorptiometry was performed at lumbar spine, upper femur (femoral neck, Ward's triangle, and total area), distal tibial diaphysis, and distal tibial epiphysis in 110 male idiopathic calcium stone formers (ICSF); 49 with and 61 without hypercalciuria on free-choice diet). Results were compared with those obtained in 234 healthy male controls, using (1) noncorrected BMD, (2) BMD corrected for age, height, and BMI, and (3) a skeletal score based on a tercile distribution of BMD values at following four sites: lumbar spine, Ward's triangle, tibial diaphysis, and tibial epiphysis. After correction, BMD—and therefore also skeletal score—tended to be lower in the stone formers than in controls at five of the six measurement sites, that is, lumbar spine, upper femur, Ward's triangle, tibial diaphysis, and tibial epiphysis, limit of significance being reached for the last two sites without difference between hypercalciuric (HCSF) and normocalciuric stone formers (NCSF). Estimated current daily calcium intake was significantly lower in patients (616 + 499 mg/24 h, mean + SEM) than in controls (773 + 532, p = 0.02). Of 17 patients who in the past had received a low-calcium diet for at least 1 year, 10 had a low skeletal score (4-6) whereas only 1 had a high score (10-12; p = 0.037). Of the 12 stone formers in the study with skeletal score 4 (i.e., the lowest), 8 had experienced in the past one or more fractures of any kind versus only 19 of the remaining 77 patients with skeletal score 5-12 (p = 0.01). Significant correlations were found between corrected BMD at various sites and 24 h sulfate, uric acid and sodium excretion, and urinary pH, as well as serum uric acid concentration. BMD at tibial diaphysis was negatively correlated with pyridinoline/ creatinine concentration ratio in 24 h urine samples, and skeletal score was negatively correlated with fasting hydroxyprolinuria. In summary, there is a slight decrease in skeletal mineral content in idiopathic calcium stone formers at the tibial site that appears to be related at least in part to dietary habits (low-calcium diet and animal protein and sodium intake) experienced by these patients.
Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein-stimulated osteoclast formation in mice
Authors: Nakano Yoichiro , Watanabe Kenichi , Morimoto Isao , Okada Yosuke , Ura Kazumi , Sato Kanji , Kasono Keizo , Nakamura Toshitaka , Eto Sumiya 
Published: February 2010

Abstract
We examined the in vivo effects of recombinant murine IL-4 (rmIL-4) on spontaneous and stimulated mouse osteoclast formation. EC-GI cells, which produce PThrP and IL-1α, were explanted in nude mice. These EC-GI cell-bearing nude mice developed hypercalcemia (4.90 + 0.68 mM), and the calcium levels were decreased to near normal (3.48 + 0.73 mM, p &lt; 0.05) at day 3 by continuous infusion of rmIL-4 at a dose of 7 μg/day. When infused with 0.6 nmol/day of PTHrP(1-34) in ICR mice, rmIL-4 at a dose of 1 or 5 μg/day for 3 days caused a marked inhibitory effect on hypercalcemia induced by PTHrP(1-34) (3.73 + 0.56-2.54 + 0.14 mM, p &lt; 0.01). However, rmIL-4 alone did not change the serum calcium in mice. Histomorphometric analysis revealed that rmIL-4 inhibits both spontaneous and PTHrP(1-34)-stimulated osteoclast formation in mice, with a decrease in osteoclastic surface and in the number of osteoclasts per mm bone surface, respectively. We conclude that IL-4 inhibits spontaneous and stimulated bone resorption resulting from inhibition of osteoclast formation and modulates the development of humoral hypercalcemia of malignancy.
Abnormal bone mineralization after fluoride treatment in osteoporosis: A small-angle x-ray-scattering study
Authors: Dr. Fratzl P. , Roschger P. , Eschberger J. , Abendroth B. , Klaushofer K. 
Published: February 2010

Abstract
Sodium fluoride treatment of osteoporosis is known to stimulate bone formation and to increase bone mass, but recent clinical trials failed to prove its antifracture effectiveness. The formation of bone with abnormal structure and, therefore, increased fragility is discussed as a possible explanation. Until now, however, exact information on the mineral structure of osteoporotic bone after fluoride treatment has been lacking. Bone biopsies were taken from three patients with postmenopausal osteoporosis before and after fluoride treatment (60 mg NaF/day for 1-2 years), from one patient with iatrogenic fluorosis, as well as from three normal controls. The mineral in these samples was investigated by a combination of backscattered electron imaging and small-angle x-ray scattering. Depending on the total dose of fluoride, an increasing amount of new bone is laid down on the surface of preexisting trabeculae. Its mineral structure is identical to that of heavy fluorosis and is characterized by the presence of additional large crystals, presumably located outside the collagen fibrils. These large crystals, which are not present in the controls or in osteoporotic bone before fluoride treatment, contribute to increase the mineral density without significantly improving the biomechanical properties of the bone. The possible success of fluoride treatment depends not only on the amount of newly formed bone but also on the rate of bone turnover. Indeed, as soon as significant amounts of fluoride are present, bone turnover leads to the replacement of old (normal) bone by new (pathologically mineralized) bone. In particular, in the case of high turnover rates we expect fluoride therapy even to lead to a deterioration in the overall mechanical stability of the skeleton.
Exercise can provide protection against bone loss and prevent the decrease in mechanical strength of femoral neck in ovariectomized rats
Authors: Peng Zhiqi , Tuukkanen Juha , Väänänen Kalervo H. 
Published: February 2010

Abstract
The effect of treadmill exercise on bone loss in ovariectomized (OVX) rats was studied in two different sets of experiments. In the first experiment rats were either ovariectomized (n = 38) or sham operated (n = 18) at the age of 12 weeks. Half the OVX rats were trained twice a day for 30 minutes by running at 10 m/minute for 7 or 17 weeks. In the second experiment 40 female rats, aged 12 weeks, were divided into five groups (n = 8). One group of rats was sacrificed on day 0 for the baseline data. Other rats were sham operated or ovariectomized for 9 weeks. Half of both groups were trained using the same training program as in the first experiment. OVX reduced trabecular bone volume (TBV) in the distal femur to 42.7 and 48.3% in 8 and 18 weeks, respectively. Exercise opposed this effect significantly but could not prevent it totally. Exercise did not have any significant effect on sham-operated animals. OVX induced a 17.7 and 30.7% decrease in maximal failure load of femoral neck in 8 and 18 weeks, respectively. A corresponding decrease was also observed in the torque capacity of tibia. Exercise was able to prevent almost totally the decrease in bone strength of femoral neck, tibia, and humerus. In conclusion, our results suggest that the measurement of bone strength in aging female rat femoral neck can be used as a useful indicator of the deleterious effect of OVX in bone. These results further indicate that exercise can overcome a significant part of the decrease in trabecular bone volume and maintain the mechanical strength of femoral neck and tibial shaft in the OVX rats.
Identification of osteocalcin mrna in nonosteoid tissue of rats and humans by reverse transcription—polymerase chain reaction
Authors: Fleet James C. , Hock Janet M. 
Published: February 2010

Abstract
Diseased or necrotic tissue can become calcified in a way that resembles bone. We examined soft tissues for the presence and regulation of the mRNA for the bone-associated protein, osteocalcin (OC). RNA was isolated from liver, kidney, lung, brain, muscle, and bone of young (2 months) male SD rats and analyzed for β-actin, IGF-I, metallothionein IIa, α1 collagen, calbindin-D9k (CaBP), and OC mRNA by reverse transcription-polymerase chain reaction (RT-PCR). All PCR products but CaBP were found in bone; CaBP was present only in duodenum, kidney, and lung. OC product was detected in all tissues; the identity of the PCR product was confirmed by sequencing. Bone OC mRNA levels were calculated to be 1000-fold higher than duodenal levels. Rats fed a 0.8% strontium diet for 7 days to drive down serum 1,25-dihydroxyvitamin D3 levels [1,25(OH)2D3] and then injected with 300 ng 1,25(OH)2D3/100 body weight had increased duodenal CaBP (2.5-fold) and femur OC mRNA (2.2-fold) 24 h after treatment. Duodenal OC mRNA was unchanged. OC mRNA was found in nondiseased human aortae, and the amount of message was elevated in calcified aorta and calcified aortic plaques. These results demonstrate that (1) tissues other than bone have low basal expression of OC mRNA, (2) OC mRNA is not regulated by vitamin D in nonosteoid tissue, and (3) expression of OC mRNA in atherosclerotic aorta reflects a role for bone-forming cells in ectopic bone formation observed in certain disease conditions.
Bafilomycin A1 inhibits bone resorption and tooth eruption in vivo
Authors: Sundquist Kai T. , Marks Sandy C. 
Published: February 2010

Abstract
It has been shown that a specific inhibitor of vacuolar H+-ATPases, bafilomycin A1, inhibits bone resorption by isolated chicken osteoclasts by blocking the proton pump in the ruffled border membrane. We report here the effects of bafilomycin A1 on bone resorption in vivo. Using a cannulated osmotic minipump delivery system, we infused bafilomycin locally to the eruption pathway of permanent premolars of beagle dogs. We used pit formation by osteoclasts in vitro to estimate the concentrations and heat stability of bafilomycin to be used in vivo. In this model, osteoclasts were cultured on thin bone slices, in which they form pits indicative of resorption. After 2 weeks preincubation at 37°C, bafilomycin concentrations of 10−6 and 10−7 M but not 10−8 M completely inhibited the resorptive activity of cultured osteoclasts, and the two larger doses were chosen for use in vivo. Local delivery of 10−6 M bafilomycin to the eruption pathway of the fourth permanent mandibular premolar during mideruption inhibited tooth eruption by blocking bone resorption as assayed by radiography, light microscopy, and scanning electron microscopy. Bafilomycin at 10−7 M had similar but less intensive effects. Moreover, osteoclasts in the alveolar bone of crypts treated with 10−7 M bafilomycin A1 stained very weakly for tartrate-resistant acid phosphatase. The effect of bafilomycin on bone resorption was shown to be very local, and no side effects of treatment with bafilomycin were observed in adjacent teeth or the behavior of dogs. We report here, for the first time, inhibition of tooth eruption caused by inhibited bone resorption using bafilomycin A1 in vivo.
Bone sialoprotein is localized to the root surface during cementogenesis
Authors: Macneil R.L. , Sheng N. , Strayhorn C. , Fisher L.W. , Somerman M.J. 
Published: February 2010

Abstract
Bone sialoprotein (BSP), an RGD-containing protein with cell attachment properties, is believed to play a regulatory role in the biomineralization of various connective tissues. To determine its possible role in tooth root formation, murine dentoalveolar tissues at sequential phases of development were analyzed immunohistochemically for the presence of BSP. BSP was localized to alveolar bone and cementum at time points associated with initial mineralization of these tissues. In addition, northern blot analyses of dental follicle tissue at day 27 of tooth development indicated that BSP mRNA is expressed by dental follicle cells at a time point coincident with the initiation of cementogenesis on the peripheral tooth root surface. Collectively, these findings indicate that BSP may play an important role in the formation and mineralization of cementum.
Small-angle x-ray scattering study of dispersed crystals from bone and tendon
Authors: Wachtel Ellen , Weiner Stephen 
Published: February 2010

Abstract
A small-angle x-ray scattering study of dispersed crystals from rat bone and mineralized turkey tendon shows that the particles in both preparations have the same scattering behavior. The data are very similar to those reported by Fratzl et al.(13) for intact turkey tendon and are consistent with the crystals being plate shaped. These observations have important implications for understanding both the structure and mineralization processes of these tissues.
Interaction between current smoking, leanness, and physical inactivity in the prediction of hip fracture
Authors: Forsén Lisa , Bjørndal Arild , Bjartveit Kjell , Edna Tom-Harald , Holmen Jostein , Jessen Vigleik , Westberg Gunell 
Published: February 2010

AbstractTo study the association between smoking habits and the incidence of hip fracture, adjusted for leanness and physical inactivity, a cohort study with 3 years follow-up was conducted. Subjects were 34,856 adults aged 50 years or older who attended a health screening in Nord-Trøndelag County in Norway in 1984–1986 (91% of eligible subjects in 1986, n = 38,356). Of these, 421 suffered a hip fracture during the years 1986–1989. Using Cox regression models, the relative risk (with 95% confidence interval) of suffering a hip fracture for female smokers versus nonsmokers was 1.5 (1.0–2.4). These results refer to females when the female body mass index (BMI) was set at 25 kg/m2 in the female model (the mean BMI for the smoking female population in this study). Among thinner females, however, smoking had a much stronger effect. For instance, if the female BMI was set at 20 kg/m2, the relative risk was 3.0 (1.8–5.0). The relative risk of hip fracture for male smokers versus nonsmokers was 1.8 (1.2–2.9) irrespective of BMI. Smoking is associated with incidence of hip fracture in both sexes and also after adjusting for body mass index and physical inactivity (the effect of physical inactivity was adjusted for self-reported ill health because ill health was included in the model). For lean females, the association with current smoking was large, as large as if they added 10 years to their age.