bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accretion of Bone Mass and Strength with Parathyroid Hormone Prior to the Onset of Estrogen Deficiency Can Provide Temporary Beneficial Effects in Skeletally Mature Rats
Authors: Shen V. , Birchman R. , Liang X. G. , Wu D. D. , Dempster D. W. , Lindsay R. 
Published: April 2006

Abstract
Intermittent administration of parathyroid hormone (PTH) has been shown to be an anabolic agent for animal and human skeletons. In previous studies, PTH has been used concurrent with, or subsequent to, the onset of bone loss. However, it is entirely possible that PTH may be used as an anabolic agent in a situation where there is stable skeletal remodeling. Increasing bone mass at this time might confer long-lasting beneficial effects when bone loss begins, for example, subsequent to the loss of ovarian function. To test this hypothesis, we evaluated the effects of administering rat PTH(1–34) (80 μg/kg/day, subucutaneously [sc]) to 6-month-old rats for a 2-week period prior to ovariectomy, and followed the natural occurrence of bone loss over a 14-week period. To determine the effects of estrogen intervention on bone gained by PTH treatment, one group was repleted with 17β-estradiol (10 μg/kg/day via sc implant). Serial measurements of bone mass in vivo at the distal femur were obtained at 2-week intervals using dual-energy X-ray absorptiometry, while histologic and mechanical strength data were obtained from excised proximal tibiae and distal femurs after sacrifice. Two weeks of PTH treatment resulted in an increase of bone mineral density (BMD), mechanical strength, and cancellous bone volume (CnBV/TV). Four weeks after PTH withdrawal, significant residual beneficial effects on BMD and strength, irrespective of ovarian status, were observed. However, 14 weeks after PTH withdrawal, although there were still residual effects on CnBV/TV in ovariectomized animals pretreated with PTH, the PTH effects on BMD and mechanical strength had been lost. Estradiol repletion during the rapid bone loss phase following ovariectomy prevented the reduction in BMD associated with either ovariectomy or PTH withdrawal. Our results suggest that: treatment of rats with PTH prior to ovariectomy produces an increase in BMD and strength, these beneficial effects extend for a period of at least three times the treatment duration, the BMD that is lost when PTH is discontinued equates to the amount accrued during the PTH treatment, estrogen replacement can be used to maintain the bone gained as a result of PTH treatment.
The Side-to-Side Differences of Bone Mass at Proximal Femur in Female Rhythmic Sports Gymnasts
Authors: Wu J. , Ishizaki S. , Kato Y. , Kuroda Y. , Fukashiro S. 
Published: April 2006

Abstract
This cross-sectional study examined the side-to-side differences of the bone mineral density (BMD) at proximal femora in female rhythmic sports gymnasts (RSGs). The hypothesis on which the study is based is that gymnasts use a different leg in take-off (left leg) and in landing (right leg) and therefore differ in the loading for the left and right legs. The gymnasts made up two groups: the regular group, which consisted of 15 regular players who had trained for about 28 h/week, and the substitutes group, which consisted of 8 substitute players who had trained for about 12 h/week. The control group consisted of 10 nonathletic college women who had not participated in any kind of regular sports activity. BMD (g/cm2) was measured in three hip sites using the XR-26 dual-energy X-ray absorptiometer scanner. Muscle strength at knee extensors (EXT) and flexors (FLX) was examined using an isokinetic dynamometer (CYBEX6000), and the vertical ground reaction force was determined with a force platform during take-off and landing movements. In the regular players, the BMDs of the left leg were significantly higher than those of the right leg at the femoral necks, greater trochanters, and Ward's triangles (p &lt; 0.01 ∼ 0.005). The side-to-side differences were 4.7 ∼ 9.6%. Regarding the strength parameters, the left side was greater than the right side significantly at EXT 60°/s (p &lt; 0.01), although the overall side-to-side difference was small. In the substitutes, the BMDs at the three sites mentioned above were also higher in the left leg than the right, but the side-to-side difference was statistically significant only at Ward's triangles (9.3%, p &lt; 0.05). The side-to-side difference of strength was not significant. In the controls, there were small left-to-right differences of the BMDs, ranging from −1.8 to 0.5%, which was significantly lower than in the regular players at each site. The overall average strength measurements were larger in the right leg than in the left except at the 120°/s. The side-to-side difference was statistically significant at EXT 30°/s and 60°/s (p &lt; 0.05). The peak force was greater in take-off than in landing, and the unit time force during take-off was significantly greater than that during landing (p &lt; 0.001). In conclusion, regarding the side-to-side difference of the BMD at proximal femora, our results demonstrate: that the left leg for take-off had higher measurements than the right leg for landing in both gymnasts' groups, which accounts for the vertical ground reaction force during take-off being greater than that during landing; that the difference in the regular players group was greater than that in the substitute group, which can be explained because the regular players practiced much more than the substitutes did; and that there was no difference in the control group.
Interleukin-1 Represses COLIA1 Promoter Activity in Calvarial Bones of Transgenic ColCAT Mice In Vitro and In Vivo
Authors: Harrison John R. , Kleinert Lisa M. , Kelly Penny L. , Krebsbach Paul H. , Woody Charles , Clark Stephen , Rowe David W. , Lichtler Alexander C. , Kream Barbara E. 
Published: April 2006

Abstract
Interleukin-1 (IL-1) inhibits collagen synthesis in osteoblastic cell lines and primary osteoblast-like cells. However, promoter elements regulating type I collagen A1 (COLIA1) expression in vivo and in organ culture may differ from those regulating expression in cell culture. We have examined the effects of IL-1 on reporter gene activity in neonatal transgenic mouse calvariae bearing COLIA1 promoter-chloramphenicol acetyltransferase (ColCAT) fusion genes. The parent construct, ColCAT 3.6, contains 3.5 kb of 5′ flanking sequence and 115 bp of 5′ untranslated region fused to the CAT reporter. In 48-h calvarial organ cultures, IL-1 repressed ColCAT 3.6 promoter activity and collagen synthesis in a dose-related manner, with a maximal inhibition of 40–65%. This repression was retained in 5′ deletion constructs truncated to −1719 bp. The inhibition of transgene mRNA was blocked by cycloheximide, indicating a requirement for new protein synthesis. Pretreatment with indomethacin diminished the inhibitory effect of IL-1 on CAT activity and collagen synthesis, suggesting partial mediation by prostaglandins. Local in vivo injection of IL-1 (500 ng) decreased calvarial transgene mRNA after 8 h, an effect that was partially blocked by indomethacin. ColCAT transgenic mice represent a useful model for in vitro and in vivo assessment of COLIA1 promoter regulation by cytokines and other factors.
Increased Interleukin-6 Production in Mouse Osteoblastic MC3T3-E1 Cells Expressing Activating Mutant of the Stimulatory G Protein
Authors: Motomura Takashi , Kasayama Soji , Takagi Miki , Kurebayashi Shogo , Matsui Hideo , Hirose Takahisa , Miyashita Yoshihiro , Yamauchi-Takihara Keik , Yamamoto Takehisa , Okada Shintaro , Kishimoto Tadamitsu 
Published: April 2006

Abstract
The McCune–Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, café-au-lait spots, and multiple endocrine hyperfunction. An activating missense mutation of the α subunit of the Gs protein (Gsα) was found in several affected tissues, resulting in prolonged stimulation of adenylate cyclase. Our recent study has indicated that the cells derived from the fibrous bone dysplasia tissues in MAS patients produced increased levels of interleukin-6 (IL-6), which may be responsible for the increased bone resorption in this disease. In the present investigation, to analyze the molecular mechanism of the increased IL-6 production by activating mutant Gsα in bone cells, we established mouse osteoblastic MC3T3-E1 cells stably transfected with the activating mutant Gsα expression vector. These cells showed a significant increase of intracellular cAMP levels and produced a higher amount of IL-6 than the cells transfected with control vector or wild-type Gsα expression vector. Analysis of the IL-6 promoter revealed that any of the AP-1, nuclear factor (NF)-IL6, and NF-κB binding elements are important for the activating mutant Gsα-induced gene expression. Electrophoretic mobility-shift assays using nuclear extracts of the mutant Gsα-expressing cells showed that phospho(Ser133)-cAMP-responsive element binding protein (CREB), AP-1, NF-IL6, and NF-κB were increased, compared with the control cells or the wild-type Gsα-expressing cells. These results indicate that activating mutant Gsα increases the transcriptional factors binding to CRE, AP-1, NF-IL6, and NF-κB elements to induce IL-6 gene expression in the osteoblastic cells.
Mice Lacking Osteopontin Show Normal Development and Bone Structure but Display Altered Osteoclast Formation In Vitro
Authors: Rittling Susan R. , Matsumoto Hiroko N. , Mckee Marc D. , Nanci Antonio , An Xiao-Rong , Novick Kristine E. , Kowalski Aaron J. , Noda Masaki , Denhardt David T. 
Published: April 2006

Abstract
We have used homologous recombination in embryonic stem cells to generate mice with a targeted disruption of the osteopontin (Opn, or Spp1, for secreted phosphoprotein 1) gene. Mice homozygous for this disruption fail to express osteopontin (OPN) as assessed at both the mRNA and protein level, although an N-terminal fragment of OPN is detectable at extremely low levels in the bones of −/− animals. The Opn−/− mice are fertile, their litter size is normal, and they develop normally. The bones and teeth of animals not expressing OPN are morphologically normal at the level of light and electron microscopy, and the skeletal structure of young animals is normal as assessed by radiography. Ultrastructurally, proteinaceous structures normally rich in OPN, such as cement lines, persist in the bones of the Opn−/− animals. Osteoclastogenesis was assessed in vitro in cocultures with a feeder layer of calvarial osteoblast cells from wild-type mice. Spleen cells from Opn−/− mice cells formed osteoclasts 3- to 13-fold more frequently than did control Opn+/+ cells, while the extent of osteoclast development from Opn−/− bone marrow cells was about 2- to 4-fold more than from the corresponding wild-type cells. Osteoclast development occurred when Opn−/− spleen cells were differentiated in the presence of Opn−/− osteoblasts, indicating that endogenous OPN is not required for this process. These results suggest that OPN is not essential for normal mouse development and osteogenesis, but can modulate osteoclast differentiation.
Response of Biochemical Markers of Bone Turnover to Hormone Replacement Therapy: Impact of Biological Variability
Authors: Hannon Rosemary , Blumsohn Aubrey , Naylor Kim , Eastell Richard 
Published: April 2006

Abstract
Biochemical markers of bone turnover may be useful to monitor patients taking hormone replacement therapy (HRT). The aim of this study was to assess the utility of markers in monitoring HRT by comparing the response of a large panel of markers to HRT with their within subject variability. We measured the response of markers to transdermal estradiol in 11 postmenopausal women over 24 weeks. We measured the within subject variability of markers in 11 untreated healthy postmenopausal women over the same period. The mean decrease in markers of bone formation after 24 weeks treatment ranged from 19% for procollagen type I C-terminal propeptide (PICP) to 40% for procollagen type I N-terminal propeptide (PINP). The mean decrease in markers of bone resorption ranged from 10% for tartrate-resistant acid phosphatase (TRAP) to 67% for C-terminal cross-linked telopeptide. The least significant change (LSC at p &lt; 0.05), calculated from the within subject variability in the untreated group, was used to define response. LSC for osteocalcin was 21%, bone alkaline phosphatase 28%, PICP 24%, PINP 21%, type I collagen telopeptide 28%, TRAP 17%, urinary calcium 90%, hydroxyproline 75%, total deoxypyridinoline 47%, free pyridinoline 36%, free deoxypyridinoline 26%, N-terminal cross-linked telopeptide 70%, and C-terminal cross-linked telopeptide 132%. The greatest number of responders after 24 weeks of treatment were found using PINP and osteocalcin (9 each), and free deoxypyridinoline (8 each) and total deoxypyridinoline (7 each). Lumbar spine bone mineral density defined four patients as responders. The ability to detect a response differs between markers and is not dependent on the magnitude of response to therapy.
In Vivo High Resolution MRI of the Calcaneus: Differences in Trabecular Structure in Osteoporosis Patients
Authors: Link Thomas M. , Majumdar Sharmila , Augat Peter , Lin John C. , Newitt David , Lu Ying , Lane Nancy E. , Genant Harry K. 
Published: April 2006

Abstract
The purpose of this study was to use high resolution (HR) magnetic resonance (MR) images of the calcaneus to investigate the trabecular structure of patients with and without osteoporotic hip fractures and to compare these techniques with bone mineral density (BMD) in differentiating fracture and nonfracture patients. Axial and sagittal HR MR images of the calcaneus were obtained in 50 females (23 postmenopausal patients with osteoporotic hip fractures and 27 postmenopausal controls). A three-dimensional gradient–echo sequence was used with a slice thickness of 500 μm and in plane resolution of 195 × 195 μm. Texture analysis was performed using morphological features, analogous to standard histomorphometry and fractal dimension. Additionally, BMD measurements of the hip (dual-energy X-ray absorptiometry) were obtained in all patients. Significant differences between both patient groups were obtained using morphological parameters and fractal dimension as well as hip BMD (p &lt; 0.05). Odds ratios for the texture parameters apparent (app.) bone volume/total volume and app. trabecular separation were higher than for hip BMD. Receiver operator characteristic values of texture measures and hip BMD were comparable. In conclusion, trabecular structure measures derived from HR MR images of the calcaneus can differentiate between postmenopausal women with and without osteoporotic hip fractures.
Camurati-Engelmann Disease: Two Case Reports Describing Metadiaphyseal Dysplasia Associated with Cerebellar Ataxia
Authors: Kormas Nic , Diamond Terry , Shnier Ronnie 
Published: April 2006

Abstract
This clinical report describes two patients presenting with progressive diaphyseal dysplasia (Camurati–Engelmann Disease) and cerebellar ataxia. The clinical and magnetic resonance imaging findings of the bony and cerebellar lesions are presented.
Identification of a Membrane Receptor for 1,25-Dihydroxyvitamin D3 Which Mediates Rapid Activation of Protein Kinase C
Authors: Nemere I. , Schwartz Z. , Pedrozo H. , Sylvia V. L. , Dean D. D. , Boyan B. D. 
Published: April 2006

Abstract
This paper is the first definitive report demonstrating a unique membrane receptor for 1,25-dihydroxyvitamin D3(1,25(OH)2D3) which mediates the rapid and nongenomic regulation of protein kinase C (PKC). Previous studies have shown that 1,25(OH)2D3 exerts rapid effects on chondrocyte membranes which are cell maturation-specific, do not require new gene expression, and do not appear to act via the traditional vitamin D receptor. We used antiserum generated to a [3H]1,25(OH)2D3 binding protein isolated from the basal lateral membrane of chick intestinal epithelium (Ab99) to determine if rat costochondral resting zone (RC) or growth zone (GC) cartilage cells contain a similar protein and if cell maturation-dependent differences exist. Immunohistochemistry demonstrated that both RC and GC cells express the protein, but levels are highest in GC. The binding protein is present in both plasma membranes and matrix vesicles and has a molecular weight of 66,000 Da. The 66 kDa protein in GC matrix vesicles has a Kd of 17.2 fmol/ml and Bmax of 124 fmol/mg of protein for [3H]1,25(OH)2D3. In contrast, the 66 kDa protein in RC matrix vesicles has a Kd of 27.7 fmol/ml and a Bmax of 100 fmol/mg of protein. Ab99 blocks the 1,25(OH)2D3-dependent increase in PKC activity in GC chondrocytes, indicating that the 1,25(OH)2D3-binding protein is indeed a receptor, linking ligand recognition to biologic function.
Reduced Expression of Interleukin-11 in Bone Marrow Stromal Cells of Senescence-Accelerated Mice (SAMP6): Relationship to Osteopenia with Enhanced Adipogenesis
Authors: Kodama Yoshiaki , Takeuchi Yasuhiro , Suzawa Miyuki , Fukumoto Seiji , Murayama Hisashi , Yamato Hideyuki , Fujita Toshiro , Kurokawa Takahide , Matsumoto Toshio 
Published: April 2006

Abstract
Aging is associated with an increase in bone marrow adipose tissue and a reduction in bone turnover. The P6 strain of senescence-accelerated mice (SAM) exhibit an early decrease in bone mass with a reduction in bone remodeling. In the bone marrow, suppressed osteoblastogenesis and osteoclastogenesis with enhanced adipogenesis are observed. The present study was undertaken to clarify the mechanism of age-related changes in bone turnover using bone marrow cells from SAMP6 mice. Because interleukin (IL)-11 has been shown to potently inhibit adipogenesis and to stimulate osteoclast formation, the effect of IL-11 on the differentiation of bone marrow cells was examined. The impaired formation of both osteoblasts and osteoclasts was restored and the enhanced formation of adipocytes was suppressed by the addition of 10 pM recombinant human IL-11. Other cytokines that activate gp130 as a common signal transducer, IL-6 and leukemia inhibitory factor, did not have such effects. Sequence analysis of the entire coding region of IL-11 cDNA obtained from SAMP6 stromal cells revealed no mutations. Constitutively secreted IL-11 protein into culture media, and its mRNA expression stimulated by transforming growth factor β were reduced in stromal cells from SAMP6 compared with those in control mice. These results demonstrate that the expression of IL-11 is reduced in bone marrow cells of SAMP6 and suggest that the reduction in IL-11 actions is involved in the impairment of both osteoblastogenesis and osteoclastogenesis in these mice. There is a possibility that alterations in IL-11 actions may be associated with the age-related impairment in bone metabolism.
Calcitonin Receptor Binding Properties in Bone and Kidney of the Chicken During the Oviposition Cycle
Authors: Yasuoka Tadashi , Kawashima Mitsuo , Takahashi Tetsuya , Tatematsu Norichika , Tanaka Katuhide 
Published: April 2006

Abstract
The binding property of calcitonin (CT) in the membrane fraction of calvaria and kidney of egg-laying and nonlaying hens was analyzed using a [125I]CT binding assay system. Binding properties of CT receptors in both tissues satisfy the authentic criteria of a receptor-ligand interaction in terms of specificity, reversibility, and saturation. Scatchard plots revealed a single class of binding sites. Values of the equilibrium dissociation constant (Kd) and binding capacity (Bmax) in laying hens showed a decrease during the period between 3 h before and 2 h after oviposition. No change was observed in nonlaying hens. In vivo administration of 17β-estradiol or progesterone caused the decrease in Kd and Bmax values. The results suggest that the binding affinity and capacity of the CT receptor in the calvaria and the kidney of the hen may be modulated by the ovarian steroid hormone.
Variation in the Short-Term Changes in Bone Cell Activity in Three Regions of the Distal Femur Immediately Following Ovariectomy
Authors: Baldock Paul A. J. , Morris Howard A. , Need Allan G. , Moore Robert J. , Durbridge Timothy C. 
Published: April 2006

Abstract
The effect of ovariectomy (OVX) on cancellous bone in the rat is not uniform at all sites of the skeleton. We report variation in the short-term effects of adult OVX in three regions of the distal femur: the diaphysis (DIA), the metaphysis (META), and the epiphysis (EPI). Cancellous bone parameters were estimated in the three separate zones of the femora and compared with changes in bone cell activity, as estimated by osteoclast surface (Oc.S) and bone formation rate (BFR). Changes were studied for 30 days in a series of rats either sham-operated (Sham) or ovariectomized (OVX) at 7 months of age. Oc.S and BFR were elevated following OVX in all regions. The time course for the OVX-induced changes differed between regions: DIA, both Oc.S and BFR were elevated at day 9; META, Oc.S was also elevated at day 9, while the rise in BFR was delayed until day 21; EPI, Oc.S remained stable but increased relative to ovary-intact rats by day 18 due to reduced levels in the latter, but BFR did not rise until day 28. These changes in bone cell activity following OVX produced a 71% reduction of cancellous bone in the DIA and a 35% reduction in the META. In contrast, no OVX-induced bone loss was observed in the EPI. This study shows that bone cell activity increases in each region of the distal femur within the first 30 days following OVX, independent of bone loss. However, the time course of increased bone cell activity is not uniform. These data highlight the role of local factors in the response to ovarian hormone deficiency.
Changes in Bone Turnover Markers and Menstrual Function After Short-term Oral DHEA in Young Women with Anorexia Nervosa
Authors: Gordon Catherine M. , Grace Estherann , Jean Emans S. , Goodman Elizabeth , Crawford Margaret H. , Leboff Meryl S. 
Published: April 2006

Abstract
Bone loss is a serious consequence of anorexia nervosa (AN). Subnormal levels of serum dehydroepiandrosterone (DHEA) are seen in patients with AN and may be causally linked to their low bone density. We hypothesized that oral DHEA would decrease markers of bone resorption (urinary N-telopeptides [NTx]), and increase markers of bone formation (serum bone-specific alkaline phosphatase and osteocalcin [OC]). Fifteen young women (age 15–22 years) with AN were enrolled in a 3-month, randomized, double-blinded trial of 50, 100, or 200 mg of daily micronized DHEA. Blood and urinary levels of adrenal and gonadal steroids and bone turnover markers were measured. No adverse clinical side effects of DHEA were noted, and a 50 mg daily dose restored physiologic hormonal levels. At 3 months, NTx levels had decreased significantly in both the 50 mg (p = 0.018) and the 200 mg (p = 0.016) subgroups. OC levels simultaneously increased within treatment groups over time (p = 0.002). Eight out of 15 (53%) subjects had at least one menstrual cycle while on therapy. Short-term DHEA was well-tolerated and appears to normalize bone turnover in young women with AN. Resumption of menses in over half of subjects suggests that DHEA therapy may also lead to estradiol levels sufficient to stimulate the endometrium in this group of patients.