bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-1β Increases the Functional Expression of Connexin 43 in Articular Chondrocytes: Evidence for a Ca2+-Dependent Mechanism
Authors: Tonon Rossana , D'Andrea Paola 
Published: April 2006

Abstract
Cell-to-cell interactions and gap junctions-dependent communication are crucially involved in chondrogenic differentiation, whereas in adult articular cartilage direct intercellular communication occurs mainly among chondrocytes facing the outer cartilage layer. Chondrocytes extracted from adult articular cartilage and grown in primary culture express connexin 43 (Cx43) and form functional gap junctions capable of sustaining the propagation of intercellular Ca2+ waves. Degradation of articular cartilage is a characteristic feature of arthritic diseases and is associated to increased levels of Interleukin-1 (IL-1) in the synovial fluid. We have examined the effects of IL-1 on gap junctional communication in cultured rabbit articular chondrocytes. Incubation with IL-1 potentiated the transmission of intercellular Ca2+ waves and the intercellular transfer of Lucifer yellow. The stimulatory effect was accompanied by a dose-dependent increase in the expression of Cx43 and by an enhanced Cx43 immunostaining at sites of cell-to-cell contact. IL-1 stimulation induced a dose-dependent increase of cytosolic Ca2+ and activates protein tyrosine phosphorylation. IL-1-dependent up-regulation of Cx43 could be prevented by intracellular Ca2+ chelation but not by inhibitors of protein tyrosine kinases, suggesting a crucial role of cytosolic Ca2+ in regulating the expression of Cx43. IL-1 is one of the most potent cytokines that promotes cartilage catabolism; its modulation of intercellular communication represents a novel mechanism by which proinflammatory mediators regulate the activity of cartilage cells.
Congenital Hip Dysplasia and Bone Mineral Density of the Hip—a New Risk Factor for Osteoporotic Fracture?
Authors: Obermayer-Pietsch Barbara M. , Walter Daniela , Kotschan Sabine , Freigassner-Pritz Martina , Windhager R. , Leb G. 
Published: April 2006

Abstract
Decreased bone mineral density (BMD) at the hip is an important risk factor for hip fractures, which are a major socioeconomic problem in the elderly. The incidence of congenital hip dysplasia (CHD) is about 7–13% in the Middle European population. We assessed the question of whether a conservatively treated CHD may be a risk factor for low BMD at the hip in adult women. We evaluated prospectively 240 premenopausal women (33 ± 7 years). Past medical history was recorded including the presence or absence of CHD. Lumbar and femoral BMD using dual-energy X-ray absorptiometry (DXA) and biochemical parameters of bone metabolism were measured. X-rays of the pelvis were performed in CHD patients. Thirty-one (12.9%) of the patients had a history of conservatively treated CHD, four (1.2%) had undergone surgery; all other patients served as control group. Patients and controls were comparable for anthropometric data, lifestyle factors, and hip axis length. BMD in CHD patients was significantly lower at the hip (difference by 1 STD) but comparable at the spine. OC was significantly higher in patients with CHD than in controls. In a logistic regression model, CHD was associated with a 6.3-fold increased risk for low BMD at the hip. We therefore conclude that a history of conservatively treated CHD may be a major risk factor for low BMD at the hip in about 1 out of 10 women. Whether this translates into an increased risk for future hip fractures will have to be assessed in further prospective studies.
Phosphatidylinositol 3-Kinase Translocates to the Nucleus of Osteoblast-Like MC3T3-E1 Cells in Response to Insulin-Like Growth Factor I and Platelet-Derived Growth Factor But Not to the Proapoptotic Cytokine Tumor Necrosis Factor α
Authors: Martelli Alberto M. , Borgatti Paola , Bortul Roberta , Manfredini Massimiliano , Massari Leo , Capitani Silvano , Neri Luca M. 
Published: April 2006

Abstract
Changes in the metabolism of nuclear inositides phosphorylated in the D3 position of the inositol ring, which may act as second messengers, mainly have been linked to cell differentiation. To clarify a possible role of this peculiar class of inositides also during cell proliferation and/or apoptosis, we have examined the issue of whether or not in the osteoblast-like clonal cell line MC3T3-E1 it may be observed an insulin-like growth factor-I (IGF-I)- and platelet-derived growth factor (PDGF)-dependent nuclear translocation of an active phosphatidylinositol 3-kinase (PI 3-K). We found that both the growth factors increased rapidly and transiently both the amount and the activity of immunoprecipitable nuclear PI 3-K. Intranuclear PI 3-K exhibited a massive tyrosine phosphorylation on the p85 regulatory subunit. Moreover, by means of coimmunoprecipitation experiments, we showed the presence, in isolated nuclei, of the p110β catalytic subunit of PI 3-K. Enzyme translocation was blocked by the specific PI 3-K inhibitor LY294002. In contrast, intranuclear translocation of PI 3-K did not occur in response to the proapoptotic cytokine tumor necrosis factor α (TNF-α). IGF-I was able to counteract the apoptotic stimulus of TNF-α and this was accompanied by the intranuclear translocation of PI 3-K. LY294002 inhibited both intranuclear translocation of PI 3-K and the rescuing effect of IGF-I. These findings strongly suggest that an important step in the signaling pathways that mediate both cell proliferation and survival is represented by the intranuclear translocation of PI 3-K.
Mechanically Strained Cells of the Osteoblast Lineage Organize Their Extracellular Matrix Through Unique Sites of αVβ3-Integrin Expression
Authors: Wozniak Magdalena , Fausto Aurora , Carron Christopher P. , Meyer Deborah M. , Hruska Keith A. 
Published: April 2006

Abstract
Bone cells transduce mechanical signals into anabolic biochemical responses. However, the mechanisms of mechanotransduction are unknown. To address this issue, we performed studies in primary cells of the human osteoblast lineage grown on collagen/vitronectin-coated supports. We discovered that mechanical strain stimulated a redistribution of the αvβ3-integrin to irregular plaque-like areas at the cell-extracellular matrix surface. Proteins involved in integrin-matrix interactions in focal adhesions, vinculin and talin, did not localize to the plaque-like areas of αvβ3-expression, but signaling molecules such as focal adhesion kinase (FAK) did. Mechanical strain increased the number and size of the plaques defined by surface expression of αvβ3-integrin. Osteopontin was secreted as a cross-linked macromolecular complex, likely through the action of tissue transglutaminase that also was found in the plaques of αvβ3-integrin cell-matrix interaction. Mechanical strain increased mineralization of the extracellular matrix that developed in these plaques in αvβ3-integrin-dependent manner. Because the plaque-like areas of cell-matrix interaction exhibit macromolecular assembly and mineralization, we conclude that they may represent subcellular domains of bone formation and that αvβ3-integrin activation represents one mechanism by which mechanical strain stimulates bone formation.
Human Bone Cell Hyperpolarization Response to Cyclical Mechanical Strain Is Mediated by an Interleukin-1β Autocrine/Paracrine Loop
Authors: Salter D. M. , Wallace W. H. B. , Robb J. E. , Caldwell H. , Wright M. O. 
Published: April 2006

Abstract
Mechanical stimuli imparted by stretch, pressure, tension, fluid flow, and shear stress result in a variety of biochemical responses important in bone (re)modeling. The molecules involved in the recognition and transduction of mechanical stimuli that lead to modulation of bone cell function are not yet fully characterized. Cyclical pressure-induced strain (PIS) induces a rapid change in membrane potential of human bone cells (HBC) because of opening of membrane ion channels. This response is mediated via integrins and requires tyrosine kinase activity and an intact actin cytoskeleton. We have used this electrophysiological response to further study the signaling events occurring early after mechanical stimulation of HBC. Stimulation of HBC at 0.33Hz PIS, but not 0.104 Hz PIS, results in the production of a transferable factor that induces membrane hyperpolarization of unstimulated HBC. The production of this factor is inhibited by antibodies to β1-integrin. Interleukin-1β (IL-1β) and prostaglandin E2 (PGE2) were identified as candidate molecules for the transferable factor as both were shown to induce HBC hyperpolarization by opening of small conductance calcium-activated potassium channels, the means by which 0.33 Hz PIS causes HBC hyperpolarization. Antibodies to IL-1β, but not other cytokines studied, inhibit the hyperpolarization response of HBC to 0.33 Hz PIS. Comparison of the signaling pathways required for 0.33 Hz PIS and IL-1β-induced membrane hyperpolarization shows that both involve the phospholipase C/inositol triphosphate pathway, protein kinase C (PKC), and prostaglandin synthesis. Unlike 0.33 Hz PIS-induced membrane hyperpolarization, IL-1β-induced hyperpolarization does not require tyrosine kinase activity or an intact actin cytoskeleton. These studies suggest that 0.33 Hz PIS of HBC induces a rapid, integrin-mediated, release of IL-1β with a subsequent autocrine/paracrine loop resulting in membrane hyperpolarization. IL-1β production in response to mechanical stimuli is potentially of importance in regulation of bone (re)modeling.
Collagen Structure Regulates Fibril Mineralization in Osteogenesis as Revealed by Cross-Link Patterns in Calcifying Callus
Authors: Wassen M. H. M. , Lammens J. , Tekoppele J. M. , Sakkers R. J. B. , Liu Z. , Verbout A. J. , Bank R. A. 
Published: April 2006

Abstract
Although &gt;80% of the mineral in mammalian bone is present in the collagen fibrils, limited information is available about factors that determine a proper deposition of mineral. This study investigates whether a specific collagen matrix is required for fibril mineralization. Calcifying callus from dog tibias was obtained at various times (3-21 weeks) after fracturing. At 3 weeks, hydroxylysine (Hyl) levels were almost twice as high as in control bone, gradually reaching normal levels at 21 weeks. The decrease in Hyl levels can only be the result of the formation of a new collagen network at the expense of the old one. The sum of the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) in callus matched that of bone at all stages of maturation. However, the ratio HP/LP was 2.5-4.5 times higher in callus at 3–7 weeks than in normal bone and was normalized at 21 weeks. Some 40% of the collagen was nonmineralized at the early stages of healing, reaching control bone values (≈10%) at 21 weeks. In contrast, only a small increase in callus mineral content from 20.0 to 22.6 (% of dry tissue weight) from week 3 to 21 was seen, indicating that initially a large proportion of the mineral was deposited between, and not within, the fibrils. A strong relationship (r = 0.80) was found between the ratio HP/LP and fibril mineralization; the lower the HP/LP ratio, the more mineralized the fibrils were. Because the HP/LP ratio is believed to be the result of a specific packing of intrafibrillar collagen molecules, this study implies that mineralization of fibrils is facilitated by a specific orientation of collagen molecules in the fibrils.
Effect of Vitamin K2 on Three-Dimensional Trabecular Microarchitecture in Ovariectomized Rats
Authors: Mawatari Taro , Miura Hiromasa , Higaki Hidehiko , Moro-Oka Takaaki , Kurata Kosaku , Murakami Teruo , Iwamoto Yukihide 
Published: April 2006

Abstract
Menatetrenone, a vitamin K2 with four isoprene units, has been reported to improve osteoporotic bone loss. The purpose of this investigation was to clarify the effect of menatetrenone on the three-dimensional (3D) trabecular microarchitecture in ovariectomized (OVX) rats by using microcomputed tomography (MCT). Forty-two 13-week-old female rats were used and divided into four groups: the OVX (OVX + MK-4) group treated with menatetrenone, the (OVX untreated) group, the sham-operated (Sham + MK-4) group treated with menatetrenone, and the sham-operated group not treated with menatetrenone (Sham untreated) group. OVX rats were fed a calcium-deficient diet. Menatetrenone treatment was begun just after the ovariectomy, and the mean menatetrenone oral intake over the 8-week period was adjusted to 30 mg/kg BW per day. The proximal metaphyseal region of the right tibia was evaluated by dual X-ray absorptiometry (DXA) and MCT. A parametric analysis of the reconstructed trabecular volume was carried out using bone volume fractions, the fractal dimension calculated by the 3D box-counting method, and the connectivity density as determined by topological analysis. Menatetrenone significantly increased the trabecular bone volume, fractal dimension, and connectivity in the OVX + MK-4 group compared with the OVX-untreated group (p &lt; 0.01). Our results suggest that an 8-week administration of menatetrenone protects against the loss of trabecular bone volume and its connectivity when treatment is begun just after the ovariectomy. Despite this apparent protection, it remains unknown whether it is possible to reestablish trabecular connectivity if therapeutic intervention occurs after the trabecular connectivity has been lost.
Immunosuppression with FK506 Increases Bone Induction in Demineralized Isogeneic and Xenogeneic Bone Matrix in the Rat
Authors: Dr. Voggenreiter Gregor , Assenmacher Stefan , Kreuzfelder Ernst , Wolf Markus , Kim Mi-Ran , Nast-Kolb Dieter , Schade Fritz Ulrich 
Published: April 2006

Abstract
The aim of the present study was to investigate a systemic induction of bone formation in rats by immunosuppression with FK506 (1 mg/kg body weight intraperitoneally [ip]) in a model of osteoinduction of isogeneic and xenogeneic demineralized bone matrix (DBM) for a period of 28 days. In particular, alterations of in vitro cytokine synthesis and changes of lymphocyte subsets were studied. DBM was implanted intramuscularly in the abdominal wall of Lewis rats (seven per group). Blood was sampled on days −7, 0, 7, and 28 for determination of in vitro tumor necrosis factor α (TNF-α) synthesis and lymphocyte subsets by flow cytometry (CD3+, CD4+, CD8+, CD45+, ED9+, and Ia+ antibodies). Ossicles of de novo formed bone and the tibias were removed on day 28 after double tetracycline labeling for histomorphometric analysis. Immunosuppression with FK506 significantly decreased lipopolysaccharide (LPS)-stimulated in vitro cytokine synthesis after 7 days and 28 days (p &lt; 0.05). Compared with control animals FK506 treatment significantly increased the volume of induced bone in isogeneic (2.1 ± 0.3 mm3 vs. 10.8 ± 0.9 mm3) and xenogeneic (0 mm3 vs. 4.7 ± 0.8 mm3) DBM. Bone histomorphometry of the tibias revealed that immunosuppression increased both bone formation and bone resorption, accompanied by a significant reduction in the relative trabecular area (Tb.Ar). FK506 caused a decrease in the counts of CD8+ T cells probably because of destruction or dislocation of these cells. This suggests that the amount of CD8+ cells and the degree of T cell activation in terms of mean fluorescence intensity (MFI) may be associated with bone metabolism. In support of this, statistical analysis revealed a significant positive correlation between parameters of bone formation as well as bone resorption and the CD4+/CD8+ ratio. There was a significant negative correlation between parameters of remodeling of the metaphysis of the tibia and induced bone volume (BV), respectively, and MFI values of CD3+/Ia+ cells. These findings suggest an important role of T lymphocytes in bone formation and bone resorption in vivo. FK506 caused a marked increase of bone formation in DBM. However, the conclusion that immunosuppression increases fracture healing warrants further investigation.
Hypovitaminosis D in a Sunny Country: Relation to Lifestyle and Bone Markers
Authors: Dr. Gannagé-Yared Marie-Hélène , Chemali Rana , Yaacoub Najwa , Halaby Georges 
Published: April 2006

Abstract
Hypovitaminosis D is associated with poor dietary intake and inadequate sunshine exposure. It is common worldwide, particularly in European elderly people. Information about vitamin D status in young adult populations from the Middle East is scarce. Furthermore, the relationship between hypovitaminosis D and some lifestyle factors such as style of clothing and dwelling location is not well defined. We assessed vitamin D intake and measured serum calcium, phosphorus, albumin, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary-free deoxypyridinoline (DPD) in 316 Lebanese volunteers (99 men and 217 women) aged 30–50 years; 156 were recruited from rural areas and 160 from urban areas. Fifty-one women from each area were veiled. The average daily vitamin D intake was 100.3 ± 67.9 IU and was found to be higher in men compared with women, in urban subjects compared with rural ones and in nonveiled women compared with veiled ones. The mean level of 25(OH)D was 9.71 ± 7.07 ng/ml. Hypovitaminosis D [25(OH)D &lt; 12 ng/ml] affected 72.8% of our population. It was more common in women than in men (83.9% vs. 48.5%). Severe hypovitaminosis D [25(OH)D &lt; 5 ng/ml] was observed in 30.7% of our subjects and was more prevalent in women (41.5%), particularly in the veiled ones (61.8%). 25(OH)D levels were the lowest in veiled women, and in women living in rural areas. Rural men had the highest 25(OH)D levels despite their very low vitamin D intake. In a multivariate model, inadequate vitamin D intake, urban dwelling, veil wearing, and high parity in women were independent predictors of hypovitaminosis D. 25(OH)D was related inversely to PTH and free DPD whereas osteocalcin achieved only a weak positive correlation with 25(OH)D. In the absence of information regarding time spent outdoors, our results show that hypovitaminosis D is common among young Lebanese people and is related mostly to low vitamin D intake. This should emphasize the need for more vitamin D in our population.
Primary Prevention of Glucocorticoid-Induced Osteoporosis with Intravenous Pamidronate and Calcium: A Prospective Controlled 1-Year Study Comparing a Single Infusion, an Infusion Given Once Every 3 Months, and Calcium Alone
Authors: Boutsen Y. , Jamart J. , Esselinckx W. , Devogelaer J. P. 
Published: April 2006

Abstract
The aim of this study was to compare the action of two regimens of intravenous (iv) pamidronate in the primary prevention of glucocorticoid-induced osteoporosis (GC-OP). The primary purpose of the study was to determine whether any differences in bone mineral density (BMD) appeared after 1 year. A secondary endpoint aimed at assessing the remodeling parameters in order to better understand the mechanisms of action of the various regimens. Thirty-two patients, who required first-time, long-term glucocorticoid therapy at a daily dose of at least 10 mg of prednisolone, were studied. Simultaneously with the initiation of their glucocorticoid treatment, patients also were randomly allocated to receive a single iv infusion of 90 mg of pamidronate at the start (group A); a first infusion of 90 mg of pamidronate followed, subsequently, by an iv infusion of 30 mg pamidronate every 3 months (group B); and a daily 800-mg elemental calcium supplement given as calcium carbonate (group C), which also was taken by patients in groups A and B. Patients were matched for starting glucocorticoid doses, sex, menopausal status, and hormonal replacement therapy. Lumbar spine and hip (total and subregions) BMDs were measured at the outset and repeated at 6-month intervals by dual-energy X-ray absorptiometry (DXA; Hologic QDR-2000). Bone turnover was assessed by measurement of total and bone-specific serum alkaline phosphatase activity (B-ALP), serum osteocalcin (OC), and serum C-telopeptide cross-links of type I collagen (CTX). After 1 year, the mean BMD changes for groups A, B, and C were, respectively, 1.7, 2.3, and −4.6% at the lumbar spine; 1.2, 1.2, and −3.1% at the femoral neck; 1.0, 2.6, and −2.2% for the total hip region. No difference was observed between pamidronate regimens but a highly significant difference was observed between both pamidronate regimens and the control group at the lumbar spine (p &lt; 0.001), at the femoral neck (p &lt; 0.01), and for the total hip (p &lt; 0.05). A significant decrease of serum C-telopeptide was observed, after 3 months, in groups A and B (p = 0.029), but a sustained decrease of bone resorption over time was observed only in group B. As far as BMD evolution over 1 year was concerned, iv pamidronate, given either as a single infusion or once every 3 months, effectively achieved primary prevention of GC-OP.
Vitamin C Supplement Use and Bone Mineral Density in Postmenopausal Women
Authors: Morton Deborah J. , Barrett-Connor Elizabeth L. , Schneider Diane L. 
Published: April 2006

Abstract
Vitamin C is known to stimulate procollagen, enhance collagen synthesis, and stimulate alkaline phosphatase activity, a marker for osteoblast formation. Studies of dietary vitamin C intake and the relation with bone mineral density (BMD) have been conflicting, probably because of the well-known limitations of dietary nutrient assessment questionnaires. The purpose of this study was to evaluate the independent relation of daily vitamin C supplement use with BMD in a population-based sample of postmenopausal women. Subjects were 994 women from a community-based cohort of whom 277 women were regular vitamin C supplement users. Vitamin C supplement use was validated. Daily vitamin C supplement intake ranged from 100 to 5000 mg; the mean daily dose was 745 mg. Average duration of use was 12.4 years; 85% had taken vitamin C supplements for more than 3 years. BMD levels were measured at the ultradistal and midshaft radii, hip, and lumbar spine. After adjusting for age, body mass index (BMI), and total calcium intake, vitamin C users had BMD levels approximately 3% higher at the midshaft radius, femoral neck, and total hip (p &lt; 0.05). In a fully adjusted model, significant differences remained at the femoral neck (p &lt; 0.02) and marginal significance was observed at the total hip (p &lt; 0.06). Women taking both estrogen and vitamin C had significantly higher BMD levels at all sites. Among current estrogen users, those also taking vitamin C had higher BMD levels at all sites, with marginal significance achieved at the ultradistal radius (p &lt; 0.07), femoral neck (p &lt; 0.07), and total hip (p &lt; 0.09). Women who took vitamin C plus calcium and estrogen had the highest BMD at the femoral neck (p = 0.001), total hip (p = 0.05), ultradistal radius (p = 0.02), and lumbar spine. Vitamin C supplement use appears to have a beneficial effect on levels of BMD, especially among postmenopausal women using concurrent estrogen therapy and calcium supplements.