bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of the 1,25-dihydroxyvitamin D3-24-hydroxylase gene in rat intestine: Response to calcium, vitamin D3 and calcitriol administration in vivo
Authors: Lemay Jacques , Demers Christian , Hendy Geoffrey N. , Delvin Edgard E. , Gascon-Barré Marielle 
Published: February 2010

Abstract
The 25(OH)D3/1,25(OH)2D3 24-hydroxylase (24-hydroxylase) displays an induction profile responsive to vitamin D (D) abundance and is hence only observed in normal extracellular Ca2+ concentrations. However, the participation of Ca2+ in the expression of the 24-hydroxylase gene in vivo is not known. The present studies investigate the role played by the circulating Ca2+ and the D3 and/or 1,25(OH)2D3 status on the 1,25(OH)2D3-mediated inducibility of the 24-hydroxylase gene in rat duodenum. Hypocalcemic D-depleted rats were supplemented with calcium alone to normalize serum Ca2+ without normalizing the D3 status or were acutely or chronically supplemented with D3 or 1,25(OH)2D3. Messenger RNA for the 24-hydroxylase was undetectable in the intestine of hypocalcemic D-depleted rats, and short- or long-term calcium supplementation was completely unsuccessful in inducing its expression. By contrast, acute 1,25(OH)2D3 administration led to significant increases in the levels of expression of the gene which was independent of the calcium intake, the prevailing circulating Ca2+, and the D3 or 1,25(OH)2D3 status. Moreover, 24-hydroxylase gene expression was only found to respond to acutely administered 1,25(OH)2D3, the mRNA levels being unaltered following continuous exposure to physiological or pharmacological doses of the hormone for 7 days. Time-course studies revealed, however, that induction of the gene was clearly apparent early in the 1,25(OH)2D3 supplementation course but gradually faded by 3 days to return to basal uninduced levels by 7 days, suggesting the presence of intestinal adaptation mechanism(s) which down-regulated the responsiveness in the continuous presence of 1,25(OH)2D3. Our data show the lack of effect of calcium alone or in combination with 1,25(OH)2D3 on the in vivo induction of the 24-hydroxylase gene expression in rat intestine. By rapidly reacting to surges in 1,25(OH)2D3 concentrations, the 24-hydroxylase efficiently controls the amount of 1,25(OH)2D3 in intestine as the first step in the biotransformation pathway aimed at the irreversible clearance of the secosteroid hormone. (J Bone Miner Res 1995;10:1148–1157)
Vitamin D status and sex hormone binding globulin: Determinants of bone turnover and bone mineral density in elderly women
Authors: Ooms Marcel E. , Lips Paul , Roos Jan C. , van der Vijgh Wim J. F. , Popp-Snijders Corrie , Bezemer P. Dick , Bouter Lex M. 
Published: February 2010

Abstract
To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density (BMD) in elderly women, BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry, in 330 healthy women aged 70 and over. Vitamin D metabolites, sex hormone binding globulin (SHBG), PTH(1–84), osteocalcin, alkaline phosphatase, and hydroxyproline and calcium excretion in 2 h fasting urine were measured. Multiple linear regression was used to adjust for potential confounders. In 65% of the women, serum 25(OH)D was below 30 nmol/l. Only values below a threshold for 25(OH)D were negatively related to serum PTH(1–84) (p = 0.02, threshold at 25 nmol/l) and to osteocalcin levels (p = 0.04, threshold at 30 nmol/l). BMD of the femoral neck and trochanter was positively related to serum 25(OH)D (left neck p = 0.001) with thresholds at 30 nmol/l whereas the distal radius was not (p = 0.32). Serum PTH was negatively related to BMD at all measurement sites (all p &lt; 0.001). Serum SHBG, an inverse measure of estrogen activity, was positively related to osteocalcin levels (p = 0.004) and the urinary hydroxyproline/creatinine ratio (p = 0.002) and negatively related to the BMD of the trochanter (left trochanter p = 0.02) and the distal radius (p = 0.001). We conclude that in elderly women, serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover. SHBG is positively related to bone turnover. Vitamin D deficiency especially influences BMD of the femoral neck, a cortical area. SHBG mainly influences BMD at the trochanteric region and distal radius, predominantly trabecular areas, which may reflect the effects of remaining estrogen activity.
Cloning and complete coding sequence of a novel human cathepsin expressed in giant cells of osteoclastomas
Authors: Li Yi-Ping , Alexander Mary , Wucherpfennig Anne L. , Yelick Pamela , Chen Wei , Stashenko Philip 
Published: February 2010

Abstract
A gene encoding a possible novel human cathepsin, a cysteine proteinase that is distinct from previously characterized enzymes, has been identified by differential screening of a human osteoclastoma cDNA library. This molecule, termed cathepsin X, appears to represent the human homolog of the osteoclast-expressed rabbit cathepsin OC-2. Cathepsin X (GenBank accession number U20280) is 93.9% identical to OC-2 at the amino acid level, and is 92% identical at the nucleotide level within the coding region. Cathepsin X is 52.2 and 46.9% identical to cathepsins S and L, respectively, and is therefore clearly distinct from these enzymes. Cathepsin X mRNA was localized to multinucleated giant cells within the osteoclastoma tumor by in situ hybridization. These data strongly support the hypothesis that cathepsin X represents a novel cysteine proteinase which is expressed at high levels in osteoclasts.
Changes in bone mineral density and markers of bone remodeling during lactation and postweaning in women consuming high amounts of calcium
Authors: Cross Nanna A. , Hillman Laura S. , Allen Susan H. , Krause Gary F. 
Published: February 2010

Abstract
A randomized clinical intervention trial to determine effects of lactation and 1 g of calcium (Ca) on bone remodeling was conducted in 15 women (calcium = 7, placebo [P] = 8) consuming 1.3–2.4 g of Ca/day from diet + prenatal supplement. Study periods were baseline, ≤2 weeks postpartum; lactation, 3 months lactation; and postweaning, 3 months postweaning. Bone mineral density (BMD) corrected for body weight was determined by dual-energy X-ray absorptiometry (DXA). Indicators of calcium metabolism, bone turnover, and lactation were measured: calcium metabolism, parathyroid hormone (PTH), 25-hydroxyvitamin D (25[OH]D), 1,25-dihydroxyvitamin D (1,25[OH]2D); bone turnover, formation, procollagen I carboxypeptides (PICP), osteocalcin, and bone alkaline phosphatase (B-ALP), resorption, tartrate resistant acid phosphatase (TRAP); and lactation, prolactin (PRL). Mean BMD changes differed by site: baseline to lactation –4.3% (P) (p &lt; 0.04) and –6.3% (Ca) (p &lt; 0.01) at the lumbar spine (L2–L4) and 5.7% gains of the ultradistal (UD) radius (Ca) (p &lt; 0.04); lactation to postweaning, –6% to –11% at all sites of the radius and ulna (Ca, P) (p &lt; 0.04) +3% at L2–L4 (Ca) (p &lt; 0.03); baseline to postweaning, (UD) radius –5.2% (P) (p &lt; 0.03), UD radius + ulna –6% to –8% (Ca, P) (p &lt; 0.04) but no significant loss of L2–L4 or total body. Bone turnover markers were higher at lactation than postweaning: PICP (+34%, p &lt; 0.001), osteocalcin (+25%, p &lt; 0.01), TRAP (+11%, p &lt; 0.005) as was PRL (+81%, p &lt; 0.001). Indicators of calcium metabolism were higher postweaning than lactation for PTH (+40%, p &lt; 0.01) and 25(OH)D (+45%, p &lt; 0.02) but not for 1,25(OH)2D. There were no differences between P or Ca for indices of calcium metabolism, bone turnover, or PRL. An increase in markers of bone turnover and a loss of BMD of the spine during lactation appears to be part of the physiological changes of lactation and not preventable by increasing calcium intake above the recommended dietary allowance (RDA). A return of BMD toward baseline of the spine but not the arm, was associated with an increase in PTH without an increase in 1,25(OH)2D postweaning. Loss of estrogen during lactation and a return postweaning may play an important role.
EndothelinB receptor activation enhances parathyroid hormone-induced calcium signals in UMR-106 cells
Authors: Lee Suk Kyeong , Dr. Stern Paula H. 
Published: February 2010

AbstractIn studies of the regulation of parathyroid hormone (PTH) signal transduction, we observed that the peptide endothelin-1 (ET) added prior to PTH greatly increased the calcium transients elicited by PTH in UMR-106 osteosarcoma cells and mouse primary osteoblastic cells. Enhancement by ET also occurred in the presence of EGTA. The ETB receptor-specific agonist sarafotoxin 6c (S6c) likewise enhanced PTH-induced Ca2+ transients. Blocking the ETA receptor-mediated component of the ET signal with BQ123 failed to abolish enhancement of PTH responses by ET. The nonselective ETA/ETB receptor antagonist PD 142893 blocked both ET and S6c-induced enhancement of the PTH responses. Prostaglandin F1α (PGF1α) pretreatment also maximally potentiated PTH responses, whereas α-thrombin, epidermal growth factor (EGF), or prostaglandin E1 (PGE1) did not affect the PTH responses. Neither active phorbol ester nor forskolin mimicked the ET effect. The ET effect was not prevented by indomethacin, NG-mono-methylarginine, genistein, pertussis toxin, 4-aminopyridine, tetraethylammonium chloride, okadaic acid, or long-term treatment with phorbol-12,13-dibutyrate. ET pretreatment did not abolish the inhibition of PTH signals by PTH(3–34), although in ET-pretreated cells the suppression of the PTH signal by PTH(3–34) was not as great. ET pretreatment did not enhance the cAMP response to PTH; rather, there was a significant inhibition of the cAMP response. Thus, the calcium signal elicited by PTH is selectively modulated by activation of the ETB receptor. The effect of ET to enhance PTH-stimulated calcium signaling appears to be independent of prostaglandins, nitric oxide, protein tyrosine kinase, protein kinase A, K+ channel activation, or phorbol ester-activated protein kinase C.
Endogenous bone-resorbing factors in estrogen deficiency: Cooperative effects of IL-1 and IL-6
Authors: Miyaura Chisato , Kusano Kenichiro , Masuzawa Toshihide , Chaki Osamu , Onoe Yoshiko , Aoyagi Maki , Sasaki Takahisa , Tamura Tatsuya , Koishihara Yasuo , Ohsugi Yoshiyuki , Suda Tatsuo 
Published: February 2010

Abstract
Estrogen deficiency causes a marked bone loss by stimulating osteoclastic bone resorption. To explore the endogenous bone-resorbing factors involved in estrogen deficiency, we examined the bone-resorbing activity present in the supernatant fraction of mouse bone marrow collected from ovariectomized (OVX) mice. Adding bone marrow supernatants at 20–80% to organ cultures of mouse long bones dose-dependently stimulated bone resorption. The endogenous bone-resorbing activity present in bone marrow supernatants from OVX mice was much higher than that from sham-operated mice 2–4 weeks after surgery, and it was significantly diminished by indomethacin in vitro. Anti-IL-1α antibody completely neutralized the bone-resorbing activity present in bone marrow supernatants from OVX mice. Antibodies against IL-1β, IL-6, and IL-6 receptors also neutralized it, but partially. The concentration of IL-1α measured by ELISA was much higher in bone marrow supernatants than in sera, but it was not appreciably changed before or after OVX. The concentration of IL-1β in bone marrow supernatants from OVX mice was less than the detection limit. OVX stimulated IL-1 activity in bone marrow supernatants measured by means of the proliferation of thymocytes. However, the level of IL-1α present in bone marrow supernatants from OVX mice was insufficient to stimulate bone resorption. Compared with the serum concentration, bone marrow supernatants contained a much higher level of IL-6 as well, and it was further increased by OVX. However, IL-6 alone present in bone marrow supernatants from OVX mice again did not stimulate bone resorption. The concurrent addition of IL-1 (50 pg/ml), IL-6 (0.2 ng/ml), sIL-6 receptor (1 ng/ml), and PGE2 (7 ng/ml), which equaled the endogenous concentrations in bone marrow supernatants from OVX mice, co-operatively induced bone resorption. These results suggest that the enhanced bone resorption that occurs during estrogen deficiency is due to multi-factors rather than to a single factor.
Regulation of plasminogen activation, matrix metalloproteinases and urokinase-type plasminogen activator-mediated extracellular matrix degradation in human osteosarcoma cell line MG63 by interleukin-1 alpha
Authors: de Bart Anton C. W. , Dr. Quax Paul H.A. , Löwik Clemens W.G.M. , Verheijen Jan H. 
Published: February 2010

Abstract
Plasmin-mediated extracellular proteolysis has been implicated in the degradation of bone in normal and pathological conditions. Normal and malignant osteoblasts can produce both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have used the osteosarcoma cell line MG63 to address the question of whether the enhanced bone turnover in osteosarcomas is mediated by t-PA or by u-PA and to study the effect of the cytokine interleukin-1α (IL-1α), known to influence bone degradation, on the plasminogen activator production and extracellular matrix degradation in malignant osteoblastic cells. Furthermore, the effect of IL-1α on the synthesis of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) was analyzed. u-PA production by MG63 was high (approximately 180 ng/106 cells/24 h). Also t-PA and PAI-1 production was observed. u-PA production was rapidly increased in MG63 by IL-1α (10 ng/ml), whereas an effect on t-PA production was only found after a prolonged incubation and hardly any effect of IL-1α on PAI-1 production was observed. mRNA analysis revealed similar effects. u-PA receptor (u-PAR) mRNA was detectable in MG63 cells and could be increased by IL-1α after 24 h. In MG63, u-PA-mediated extracellular matrix degradation was detectable, and IL-1α increased the u-PA-mediated matrix degradation (approximately 2-fold). Under control conditions in MG63, only MMP-2, TIMP-1, and TIMP-2 mRNA could be observed. After the addition of IL-1α, a very rapid increase in MMP-1 and MMP-3 mRNA could be observed as well as a moderate increase in TIMP-1 mRNA. The presence of MMP-2 was demonstrated by gelatin zymography. These results show that IL-1α can stimulate u-PA production and can regulate extracellular proteolytic activity mainly via u-PA induction in the MG63 osteosarcoma cell line. Furthermore, IL-1α has a strong stimulating effect on the production of MMP-1 and MMP-3. These findings suggest that u-PA and possibly MMP-1 and MMP-3 play an important role in the process of bone turnover in osteosarcomas.
Microcallus formations of the cancellous bone: A quantitative analysis of the human spine
Authors: DipL. Ing. BMT Hahn Michael , Vogel M. , Amling M. , Ritzel H. , Delling G. 
Published: February 2010

Abstract
Microcallus formations are demonstrable in nearly all spongy bone by means of suitable preparation techniques. Histologically, these structures are immature fibrous bone. Their genesis, frequency, and importance are largely unknown. To address these issues, 26 normal human spines, 11 osteoporotic spines, and different parts of the skeleton (femur head, iliac crest) were investigated for microcallus using a new preparation technique—allowing a combined 2- and 3-dimensional analysis. According to our analysis, microcallus formation occurs frequently in persons older than 45 years of age. These formations are mainly localized in the lower thoracic and lumbar spine and are obviously more frequent in females than in males. In individuals with a trabecular bone volume (BV/TV) in the spine below 11%, microcallus formations occur regularly. But the number of microcallus formations depends more on the microarchitecture of the cancellous bone (trabecular bone pattern factor, TBPf), than on individual trabecular parameters (trabecular number, TbN; trabecular bone volume, BV/TV; and trabecular thickness, TbTh). In about 33% of cases microfractures are demonstrable in the center of the microcallus formation. It is unclear whether microcallus may be the result of a nontraumatic process. In therapy studies the bone mass could be misrepresented due to the amount of microcallus. Although it indicates instability of the bone structure, microcallus formation is not only a negative mechanism, but stabilizes and regenerates the bone tissue. Furthermore, complete new trabeculae can be formed due to bridges of microcallus between the remnant trabeculae. Osteoporosis is not the result of an inability to form microcallus formations.
Regulation of COL1A1 expression in type I collagen producing tissues: Identification of a 49 base pair region which is required for transgene expression in bone of transgenic mice
Authors: Bedalov Antonio , Salvatori Roberto , Dodig Milan , Kronenberg MarkS , Kapural Belinda , Bogdanovic Zoran , Kream Barbara E. , Woody Charles O. , Clark Stephen H. , Mack Kristine , Rowe David W. , Lichtler Alexander C. 
Published: February 2010

Abstract
Previous deletion studies using a series of COL1A1-CAT fusion genes have indicated that the 625 bp region of the COL1A1 upstream promoter between -2295 and -1670 bp is required for high levels of expression in bone, tendon, and skin of transgenic mice. To further define the important sequences within this region, a new series of deletion constructs extending to -1997, -1794, -1763, and -1719 bp has been analyzed in transgenic mice. Transgene activity, determined by measuring CAT activity in tissue extracts of 6- to 8-day-old transgenic mouse calvariae, remains high for all the new deletion constructs and drops to undetectable levels in calvariae containing the -1670 bp construct. These results indicate that the 49 bp region of the COL1A1 promoter between -1719 and -1670 bp is required for high COL1A1 expression in bone. Although deletion of the same region caused a substantial reduction of promoter activity in tail tendon, the construct extending to -1670 bp is still expressed in this tissue. However, further deletion of the promoter to -944 bp abolished activity in tendon. Gel mobility shift studies identified a protein in calvarial nuclear extracts that is not found in tendon nuclear extracts, which binds within this 49 bp region. Our study has delineated sequences in the COL1A1 promoter required for expression of the COL1A1 gene in high type I collagen-producing tissues, and suggests that different cis elements control expression of the COL1A1 gene in bone and tendon.
Inhomogeneity in body fat distribution may result in inaccuracy in the measurement of vertebral bone mass
Authors: Formica Carmelo , Loro Maria-Luiza , Gilsanz Vicente , Prof. Seeman Ego 
Published: February 2010

AbstractWhen bone mineral content (BMC) is measured by dual X-ray absorptiometry (DXA), the X-ray beam is attenuated by bone and soft tissue. Since the component of the attenuation caused by the soft tissue overlying bone cannot be measured, the attenuation caused by soft tissue adjacent to bone is measured and is used in the calculation of BMC. The assumption underlying this approach is that the amount and composition of this adjacent soft tissue is the same as overlying bone. The aim of this study was to examine the validity of this assumption by determining whether fat distribution over and adjacent to bone differ and whether this introduces accuracy errors in the measurement of BMC by postero-anterior (PA) and lateral scanning. BMC (posterior processes plus vertebral body, g) of the third lumbar vertebra was 17.3 ± 0.7 by PA and 17.0 ± 0.7 by lateral scanning in 27 premenopausal women (p = NS), but 2.7 g or 20% higher by PA than lateral scanning in 27 postmenopausal women (14.4 ± 0.7, 11.7 ± 0.5, p &lt; 0.01). Thus, the respective diminutions across age by PA scanning was about half that by lateral scanning (16.8 ± 3.9%, 31.2 ± 3.0%, p &lt; 0.01). Percent fat in the soft tissue baseline (lateral to bone, ST-lat) used to derive BMC by PA scanning, was higher than in the soft tissue baseline (anterior to bone, ST-ant) used to derive BMC by lateral scanning by 2.6 ± 0.7% in premenopausal women and 7.5 ± 1.0% in postmenopausal women (both p &lt; 0.01). After adjusting for these differences in percent fat, BMC by PA and lateral scanning no longer differed. Fat content (cm2) measured by quantitative computed tomography (QCT) in an additional 46 women, was higher in the soft tissue baseline (ST-lat) than anterior to bone in the 18 premenopausal (30.7 ± 4.2, 24.3 ± 3.5, p &lt; 0.01) and the 28 postmenopausal women (41.6 ± 3.7, 34.1 ± 3.5, p &lt; 0.01). Fat content in the soft tissue baseline region (ST-ant) was higher than on either side of bone in premenopausal women (31.3 ± 5.7, 26.5 ± 4.2, p &lt; 0.05) but less than on either side of bone in postmenopausal women (44.7 ± 4.3, 50.6 ± 5.1, p &lt; 0.05). In summary, the differing composition of soft tissue anterior 6and lateral to bone calls to question the validity of the assumption of tissue homogeneity needed for accurate measurement of BMC by DXA. In the elderly, BMC may be too high by PA scanning, resulting in a reduced cross-sectional diminution with age. Thus accuracy errors due to fat inhomogeneity compound those caused by osteophytes and suggests caution is needed in making inferences regarding the magnitude of age-related bone loss determined in vivo using bone densitometry.
The bone mineral status of patients with marfan syndrome
Authors: Kohlmeier Lynn , Gasner Cheryll , Bachrach Laura K. , Marcus Robert 
Published: February 2010

Abstract
Osteopenia at the hip and low total body calcium content have been reported in women with Marfan syndrome. Using dual X-ray absorptiometry (DXA), we evaluated the lumbar spine L2-L4 and proximal femur bone mineral density (BMD, g/cm2) in 32 women and 16 children with Marfan syndrome. The women were 38 ± 10 (SD) years old (23–58 years); their mean height was 178.6 ± 8 cm. The children (9 boys and 5 girls) were 9.9–17.5 years old. Children were tall for their ages but of normal weight. All subjects were moderately active, without previous nontraumatic fracture. In the women, BMD was reduced at L2–L4, femoral neck (fnk), trochanter (tr), and intertrochanter (intr) (p &lt; 0.0001–0.006), compared with age-predicted values. Z scores for L2–L4 and for the fnk, tr, and intr, were –0.59 ± 1.06, –1.25 ± 0.99, –1.03 ± 1.10, and –1.31 ± 0.91, respectively. The average hip axis length (HAL) of 11.5 ± 0.093 cm was at the 80th percentile for women. No significant change was observed in 1 year follow-up BMD measurements in 13 women (fnk = –0.23 ± 23%/year, L2–L4 = –0.43 ± 1.57%/year). In Marfan children, BMD correlated with age, height, and pubertal development. Femoral neck BMD was reduced (Z = –0.74 ± 1.22, p &lt; 0.05) with a nonsignificant trend toward decreased BMD at L2–L4 (Z = –0.33 ± 1.48). Resorption markers in Marfan women were normal and did not correlate with bone status. We conclude that women with Marfan syndrome have both axial and peripheral osteopenia as well as an increased HAL. This combination of findings likely increases substantially their long-term risk for hip fracture. Presence of osteopenia in Marfan children indicates that the skeletal deficits of Marfan syndrome may reflect inadequate bone acquisition.