bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fibronectin gene expression, synthesis, and accumulation during in vitro differentiation of chicken osteoblasts
Authors: Winnard Robert G. , Gerstenfeld Louis C. , Toma Cyril D. , Dr. Franceschi Renny T. 
Published: February 2010

Abstract
A well-defined chicken osteoblast culture system(18) has been used to examine fibronectin (FN) mRNA levels, synthesis, and accumulation during in vitro differentiation and matrix mineralization. Immunofluorescent staining of cells after 6 or 18 days in culture revealed that FN was initially associated with the cell surface and in partial coalignment with cytoskeletal elements while at the latter time most FN was associated with the extracellular matrix as a ubiquitous fibrillar network. Western blot analysis of total cell-associated proteins also detected FN at all culture times. However, when results were normalized to cellular DNA, FN levels increased until days 12–16 and remained relatively constant thereafter. Similarly, FN synthesis as measured by [35S]-methionine labeling, and immunoprecipitation was greatest in early cultures (culture day 3) and then declined such that synthesis decreased 60% at day 18 and 94% after 24–31 days. FN mRNA levels as measured by Northern blot analysis were well correlated with FN synthesis. These results clearly show that FN is made by primary osteoblasts during their in vitro maturation. In contrast to other osteoblast markers such as alkaline phosphatase, osteocalcin, and osteopontin, whose expression increases as cells differentiate, FN accumulates in the matrix during periods of early cell growth and attachment and then remains proportional to cell number. Results with FN differ from those obtained with collagen which continues to accumulate in the extracellular matrix during osteoblast maturation. These results are consistent with FN being important for the initial attachment of early osteoblasts or osteoblast precursors to the pericellular matrix.
Technical considerations of dual-energy X-ray absorptiometry-based bone mineral measurements for pediatric studies
Authors: Dr. Koo Winston W. K. , Walters Jocelyn , Bush Andrew J. 
Published: February 2010

Abstract
Dual-energy X-ray absorptiometry (DXA) measurements have been shown to provide useful information on bone mineral status in young pediatric subjects. The purpose of this study was to challenge this system under various conditions to determine the clinical and experimental parameters that may be encountered which could interfere with DXA-based bone mineral content (BMC) and bone mineral density (BMD) measurements. Variations in data acquisition, including the covering of step phantom (external calibration standard) with a cotton blanket or partial exclusion of step phantom in the scan field, tissue freezing, or the presence of small nonmetallic objects, did not significantly alter DXA BMC or BMD measurements. By contrast, the presence of movement artifact, radiographic contrast media, and nonmetallic orthopedic casts significantly interfered with DXA BMC and BMD measurements. Variability in operator-dependent analysis of DXA scans occurred with regional analysis of whole body scans for DXA BMC and BMD measurements (average coefficient of variation was 2.9% and 1%, respectively, depending on the region analyzed) but did not affect the total (whole body) result. A minor adjustment in the manual delineation of the step phantom during data analysis may result in almost a 30% difference in DXA BMC and BMD. We conclude that movement artifact, radiographic contrast media, nonmetallic orthopedic cast, and variations in operator-dependent data analysis may interfere with DXA BMC and BMD measurement in young pediatric subjects. Therefore, appropriate care should be taken to reduce or eliminate such interference.
1α,25-dihydroxyvitamin D3 inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5
Authors: Akiyama Haruhiko , Hiraki Yuji , Shigeno Chohei , Kohno Hiroaki , Shukunami Chisa , Tsuboyama Tadao , Kasai Ryuichi , Suzuki Fujio , Konishi Junji , Nakamura Takashi 
Published: February 2010

Abstract
Here we report the effects of lα,25-dihydroxyvitamin D3 [1,25(OH)2D3] in vitro on the growth and chondrogenesis of a chondroprogenitor-like clonal mouse EC cell line, 10−10 to 10−7 M ATDC5, 1,25(OH)2D3 inhibited [3H]thymidine incorporation in undifferentiated chondroprogenitor-like ATDC5 cells in time- and dose-dependent manners. 1,25(OH)2D3 suppressed cartilage-nodule formation and the accumulation of cartilage-specific proteoglycan in ATDC5 cells in a dose-dependent manner. The 1,25(OH)2D3-induced inhibition of cartilage-nodule formation was reversible and direct, unrelated to the antiproliferative action of the hormone on the undifferentiated ATDC5 cells. ATDC5 cells even in the precartilaginous stage expressed 4.4 kb vitamin D receptor (VDR) mRNA as assessed by northern blot analysis. The equilibrium saturation binding experiment revealed the presence of a single class of saturable and high-affinity binding sites for 1,25(OH)2D3 in the cytosols. These results provide evidence for the hypothesis that both recruitment and chondrogenesis of chondroprogenitors are negatively regulated by 1,25(OH)2D3 via a VDR-mediated process in vivo.
Aspirin and NSAID use in older women: Effect on bone mineral density and fracture risk
Authors: Bauer Douglas C. , Orwoll Eric S. , Fox Kathleen M. , Vogt Thomas M. , Lane Nancy E. , Hochberg Marc C. , Stone Katie , Nevitt Michael C. 
Published: February 2010

Abstract
Prostaglandin inhibition by aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) may inhibit bone loss and preserve bone mineral density (BMD) in vitro and in animal models. The effect of these agents on BMI) and fracture risk in postmenopausal women is unknown. We assessed the risk factors for osteoporosis and the use of aspirin and NSAIDs in 7786 white women over age 65. Axial BMD was measured at the same time, and fractures were prospectively documented over the subsequent 4 years of follow-up. In age-adjusted analyses, daily use of aspirin or NSAIDs was associated with a 2.3–5.8% increase in BMD of the hip and spine. The relationship persisted even after adjustment for weight, a variety of medications, self-reported arthritis, and for radiographic findings of osteoarthritis, but the multiply adjusted increase in BMD was only 1.0–3.1%. Fracture risk was similar among daily users of aspirin and NSAIDs and nonusers. After adjustment for potential confounders, among daily aspirin users the relative risk of hip fracture was 1.1 (95% confidence interval [CI]: 0.7, 1.6), and among daily NSAID users the risk was 0.9 (CI: 0.6, 1.4). Considering all nonspine fractures together, the risk among aspirin users was 1.0 (CI: 0.8. 1.2), and among NSAID users the risk was also 1.0 (CI; 0.8, 1.2). Regular use of aspirin or NSAIDs may have a modest beneficial effect on BMD in postmenopausal women. This effect persists after adjustment for obesity and the presence of osteoarthritis. However, among women who take aspirin or NSAIDs regularly, there is no clinically significant protective effect on the subsequent risk of fractures.
Aluminum potentiates the effect of fluoride on tyrosine phosphorylation and osteoblast replication in vitro and bone mass in vivo
Authors: Dr. Caverzasio Joseph , Imai Toshio , Ammann Patrick , Burgener Dominique , Bonjour Jean-Philippe 
Published: February 2010

Abstract
Osteosclerosis in workers exposed to fluoride (F) and aluminum (Al) (industrial fluorosis) led to the use of F as a treatment to increase bone mass in osteoporosis patients. Because the influence of traces of Al on the effects of F on bone formation is heretofore unknown, we have investigated this issue both in vitro and in vivo. We have found that minute amounts of Al (≤10−5 M) potentiate the effects of F in vitro such that osteoblast proliferation increased by 15 ± 2.7% at 50 μM (p &lt; 0.001) and by 117.6 ± 5.1% at 750 μM (p &lt; 0.001), concentrations of F with no mitogenic effect alone. F + Al time-dependently modulated a growth factor signaling pathway(s) associated with enhanced tyrosine phosphorylation (TyrP) of several proteins (p90 [2.9x], p77 [4.9x], p68 [9.6x], and mitogen activated protein kinases [3x]). TyrP was only slightly or not at all changed by F and Al alone, respectively. The effects of F + Al on TyrP and cell proliferation were markedly reduced by 100 μM ryrphostin-51, a tyrosine kinase inhibitor. Protein kinase A (PKA) and protein kinase C (PKC) pathways were not involved in this response. In vivo, F + Al administered for 8 months, at doses that had no effect when the minerals were administered individually, significantly enhanced proximal tibia bone mineral density (BMD) by 6.3 ± 1% compared with initial values and by 2-fold compared with control ovariectomized rats (p &lt; 0.0001). These effects are consistent with a crucial role of Al in osteosclerosis observed in industrial fluorosis. The results suggest that the combination of F + Al modulates a growth factor-dependent TyrP pathway enhancing mitogen-activated protein kinase and osteoblastic proliferation and bone mass.
Parathyroid hormone-induced resorption in fetal rat limb bones is associated with production of the metalloproteinases collagenase and gelatinase B
Authors: Witty Jean P. , Foster Shirley A. , Stricklin George P. , Matrisian Lynn M. , Stern Paula H. 
Published: February 2010

Abstract
The role of matrix metalloproteinases in parathyroid hormone (PTH)-induced bone resorption was assayed using a fetal rat limb bone culture system. Cotreatment of bones with PTH and recombinant inhibitor of metalloproteinases, TIMP-1, in vitro, inhibited the PTH-stimulated 45Ca release from the limb bones without affecting β-glucuronidase release. TIMP-1 was fully effective when added during only the final 24 h of a 72 h culture with PTH but was ineffective when added for only the first 24 h of the 72 h culture. In contrast, calcitonin (CT) was effective when added for either the first 24 or the final 24 h of the culture. Using in situ hybridization, the mRNA for collagenase was detected in mononuclear cells of cultured bone. Treatment of the bones with PTH resulted in an increase in the number of cells producing collagenase mRNA, some of which had osteoclastic morphology. PTH also caused a dramatic induction of the mRNA for the 92-kD gelatinase B metalloproteinase in both mononuclear and osteoclastic cells. There was no detectable mRNA for the metalloproteinases stromelysin-1, stromelysin-2, or matrilysin in PTH-treated or control cultures. These results suggest that PTH-induced bone resorption is mediated, at least in part, by the induction of collagenase and gelatinase B mRNA in bone cells.
Expression of osteocalcin in the patella of experimentally immobilized and remobilized rats
Authors: Kannus Pekka , Jozsa Laszlo , Kvist Martti , Järvinen Teppo L.N. , Maunu Vesa-Matti , Hurme Timo , Järvinen Markku 
Published: February 2010

Abstract
The exact mechanisms by which mechanical loading-unloading affects bone tissue are mostly unknown. Recently, osteocalcin, a direct product of osteoblasts, has been shown to reflect the activity of the mineralization phase of the newly formed bone matrix, and therefore, the in situ detection of osteocalcin could be used for studying the effects of physical activity-inactivity on the osteoblast function or bone formation in the target bone. In this study, the effect of various loading states (immobilization and three forms of subsequent remobilization) on the in situ expression of osteocalcin in the rat patellas and their osteotendinous junctions was studied immunohistochemically using a polyclonal rat antiosteocalcin as the primary antibody. Following immobilization for 3 weeks, the immunoreactivity of osteocalcin was markedly decreased or was completely absent in all the patellar areas which normally show intense reaction as a sign of mineralization of the newly formed bone, that is, in the subperiosteal and subchondral regions, in the osteoid tissue that lies on the surface of the trabecular bone, and around the cortical lacunae. The same was true in the mineralized fibrocartilage zone of the osteotendinous junction of the quadriceps tendon. Free remobilization for 8 weeks (free cage activity) could not improve the situation, but after intensified remobilization of the same duration (low and especially high intensity treadmill running) high osteocalcin expression was observed in the above-mentioned anatomic sites. These findings indicate that formation of new bone tissue is rapidly regulated by the loading states of the bone. Higher than normal activity seems to be needed to restore the bone formation from the disuseinduced depression to normal.
Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation
Authors: Kotake Shigeru , Sato Kazuto , Kim Kang Jung , Takahashi Naoyuki , Udagawa Nobuyuki , Nakamura Ichiro , Yamaguchi Akira , Kishimoto Tadamitsu , Suda Tatsuo , Kashiwazaki Sadao 
Published: February 2010

Abstract
Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction. Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.
Evidence for preservation of cortical bone mineral density in patients on continuous ambulatory peritoneal dialysis
Authors: Mottet Jean-J. , Horber Fritz F. , Casez Jean-P. , Descoeudres Claude , Jaeger Philippe 
Published: February 2010

Abstract
It is still unclear whether dialysis modality, i.e., continuous ambulatory peritoneal dialysis (CAPD) versus hemodialysis (HD) specifically affects bone mineral density (BMD). To answer this question, 34 patients on HD and 25 on CAPD were matched for age, sex, height, and body weight with 125 normal subjects. BMD was measured using dual-energy X-ray absorptiometry (DXA; Hologic QDR 1000/W) at the lumbar spine (trabecular bone), the femoral neck (mixed cortical and trabecular bone), the distal tibial diaphysis (cortical bone), and the epiphysis (trabecular bone) in all subjects. No significant difference for blood hemoglobin, albumin, total and ionized calcium, intact parathyroid hormone (PTH) or phosphorus concentrations, as well as for alkaline phosphatase activity, failed renal allograft, prior steroid therapy, prior parathyroidectomy, duration of uremia, or of dialysis was found between patients on HD and those on CAPD. However, the residual daily urine volume and renal function at the time of the absorptiometry were higher in CAPD than in HD patients (p &lt; 0.05) as well as the mean dialysate calcium concentration during dialysis, the blood bicarbonate concentration, and the residual renal function at the initiation of dialysis (p, 0.01, p &lt; 0.05, and p &lt; 0.005, respectively). In contrast, the total dose of calcium carbonate was lower in CAPD than in HD patients (p &lt; 0.01). Results of BMD were expressed as Z scores (the number of standard deviations from the appropriate mean of BMD of 623 healthy subjects adjusted for age and sex). At the lumbar spine, no significant difference with respect to BMD was observed between the three groups. At the femoral neck and tibial epiphysis, HD patients had lower BMD (p &lt; 0.001) than normal controls, whereas no difference was observed between HD and CAPD patients. At tibial diaphysis, patients on HD had lower BMD (p &lt; 0.001) than patients on CAPD and than normal controls, with the values being similar in patients on CAPD and in normal controls. The results remained identical after exact matching of HD (n = 25) and CAPD (n = 25) patients for dialysis duration (1.9 ± 03 and 1.7 ± 03 years, respectively). Multiple regression analysis revealed significant negative correlations between Z scores at the lumbar spine (p &lt; 0.05), femoral neck (p &lt; 0.02), tibial diaphysis (p &lt; 0.005), and tibial epiphysis (p &lt; 0,05) on the one hand and plasma alkaline phosphatase activity on the other. The Z score at tibial diaphysis was also correlated with residual renal function at the initiation of dialysis (p &lt; 0.05). In conclusion, this study provides evidence for the preservation of cortical bone with CAPD as opposed to HD. The higher residual renal function observed in the former treatment modality might account, at least in part, for this finding.
Juvenile paget disease: Life-long features of a mildly affected young woman
Authors: Golob Deborah S. , McAlister William H. , Mills Barbara G. , Fedde Kenton N. , Reinus William R. , Teitelbaum Steven L. , Beeki Suganthi , Dr. Whyte Michael P. 
Published: February 2010

Abstract
Unusually mild Juvenile Paget Disease (JPD) was extensively investigated in a mentally retarded 21-year-old white woman. Progressive bowing deformitity of her lower limbs began at age 1 1/2 years. Nontraumatic fractures of both femora and both tibias occurred between ages 9 and 14 years. During adulthood, cortical thickening, osteosclerosis, and bowing affected these bones. Serum alkaline phosphatase (ALP) activity was persistently elevated. We found her serum osteocalcin and urinary hydroxyproline and pyridinoline/deoxypyridinoline to also be increased. The iliac crest histology, at ages 14 and 21 years, showed wide cortices and enhanced skeletal remodeling yet the bone was exclusively lamellar. Features of classic Paget Bone Disease (PBD)-such as hypermultinucleated osteoclasts, peritrabecular fibrosis, and mosaic or woven bone-were absent. Electron microscopy revealed no cytoplasmic or nuclear inclusions. Her dermal fibroblasts in culture synthesized unremarkable levels of ALP with proper membrane topography and lipid anchoring; ALP released into the medium also appeared normal. Six months of synthetic human calcitonin therapy daily appeared to reduce her lower limb pain and warmth, but the radiographs, biochemical parameters of skeletal turnover, and bone scintigraphy were unaltered. Lamellar bone has been reported in JPD but accompanied by excessive amounts of woven bone. Our patient reveals that lamellar bone without features of PBD can characterize the skeletal histopathology of the especially rare case of mild JPD.
Comparison of three intravenous regimens of clodronate in paget disease of bone
Authors: Khan Sohail A. , Mccloskey Eugene V. , Eyres Keith S. , Nakatsuka Kiyoshi , Sirtori Paulo , Orgee Jane , Coombes Gillian , Prof. Kanis John A. 
Published: February 2010

Abstract
We compared the effects of three different regimens of intravenous clodronate in a retrospective study of 60 patients with Paget disease. A total dose of 1500 mg of clodronate was given as 300 mg for 5 consecutive days (n = 20), 1500 mg as a single infusion (n = 20), or 300 mg as a single infusion for 5 consecutive months (n = 20). The response to treatment and the duration of the effect were assessed from sequential changes in the activity of serum alkaline phosphatase. Treatment with dodronate induced a significant response in 85% of patients. The response rate was comparable in patients treated with 5 daily infusions (90%), with a single infusion (75%), and with 5 monthly infusions (90%). The median duration of response from the start of treatment was 11 months for those treated with five daily infusions and 12 months for the other two regimens. At one year, 22, 40, and 44% of patients had maintained their response in the daily, single, and monthly infusion regimen, respectively (NS). Six patients (32%) treated with 5 daily infusions achieved a remission (complete response) compared with 3 patients treated with a single infusion and 5 monthly infusions, respectively (16 and 15% respectively, NS). Patients attaining a complete response had a significantly longer duration of response compared with partial responders (median time 15.0 versus 11.5 months, respectively, p &lt; 0.05). We conclude that intravenous clodronate (total dose 1500 mg) suppresses disease activity in the majority of patients with Paget disease of bone. The degree and duration of response were similar for the three regimens. Thus, in the treatment of Paget disease, the choice of regimen is a matter of convenience.
The effect of systemically administered PDGF-BB on the rodent skeleton
Authors: Mitlak Bruce H. , Finkelman Richard D. , Hill Esther L. , Li Jun , Martin Bruce , Smith Tait , D'Andrea Mark , Antoniades Harry N. , Lynch Samuel E. 
Published: February 2010

Abstract
Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks. Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p &lt; 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%). Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone. Histomor-phometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition. We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.