bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia‐inducible factor 1α inhibits the fibroblast‐like markers type I and type III collagen during hypoxia‐induced chondrocyte redifferentiation: Hypoxia not only induces type II collagen and aggrecan, but it also inhibits type I and type III collagen in the hypoxia‐inducible factor 1α–dependent redifferentiation of chondrocytes
Authors: Duval Elise , Leclercq Sylvain , Elissalde Jean‐Marc , Demoor Magali , Galéra Philippe , Boumédiene Karim 
Published: September 2009

AbstractObjectiveAutologous chondrocyte implantation requires expansion of cells ex vivo, leading to dedifferentiation of chondrocytes (loss of aggrecan and type II collagen to the profit of type I and type III collagens). Several approaches have been described for redifferentiation of these cells. Among them, low oxygen tension has been exploited to restore the differentiated chondrocyte phenotype, but molecular mechanisms of this process remain unclear. However, under conditions of hypoxia, one of the major factors involved is hypoxia‐inducible factor 1α (HIF‐1α). The purpose of this study was to investigate the role of HIF‐1α during human chondrocyte redifferentiation.MethodsWe used complementary approaches to achieving HIF‐1α loss (inhibition by cadmium ions and dominant‐negative expression) or gain (ectopic expression and cobalt ion treatment) of function. Expression of chondrocyte, as well as fibroblast‐like, phenotype markers was determined using real‐time reverse transcription–polymerase chain reaction and Western blot analyses. Binding activities of HIF‐1α and SOX9, a pivotal transcription factor of chondrogenesis, were evaluated by electrophoretic mobility shift assays and by chromatin immunoprecipitation assay.ResultsWe found that hypoxia and HIF‐1α not only induced the expression of SOX9, COL2A1, and aggrecan, but they simultaneously inhibited the expression of COL1A1, COL1A2, and COL3A1. In addition, we identified the binding of HIF‐1α to the aggrecan promoter, the first such reported demonstration of this binding.ConclusionThis study is the first to show a bimodal role of HIF‐1α in cartilage homeostasis, since HIF‐1α was shown to favor specific markers and to impair dedifferentiation. This suggests that manipulation of HIF‐1α could represent a promising approach to the treatment of osteoarthritis.
C1q inhibits immune complex–induced interferon‐α production in plasmacytoid dendritic cells: A novel link between C1q deficiency and systemic lupus erythematosus pathogenesis
Authors: Lood Christian , Gullstrand Birgitta , Truedsson Lennart , Olin Anders I. , Alm Gunnar V. , Rönnblom Lars , Sturfelt Gunnar , Eloranta Maija‐Leena , Bengtsson Anders A. 
Published: September 2009

AbstractObjectiveC1q deficiency is the strongest risk factor known for the development of systemic lupus erythematosus (SLE), since almost all humans with a genetic deficiency of C1q develop this disease. Low C1q serum concentration is also a typical finding in SLE during flares, emphasizing the involvement of C1q in SLE pathogenesis. Recent studies have revealed that C1q has a regulatory effect on Toll‐like receptor–induced cytokine production. Therefore, we undertook this study to investigate whether C1q could regulate production of interferon‐α (IFNα).MethodsPeripheral blood mononuclear cells (PBMCs) and plasmacytoid dendritic cells (PDCs) were stimulated with 3 known interferogenic stimuli and cultured with physiologic concentrations of C1q. IFNα production was determined by an immunoassay.ResultsC1q significantly inhibited PBMC IFNα production induced by RNA‐containing immune complexes (ICs), herpes simplex virus (HSV), and CpG DNA. C1q also inhibited PDC IFNα production induced by ICs and CpG DNA but increased PDC IFNα production induced by HSV. The regulatory role of C1q was not specific for IFNα but was also seen for interleukin‐6 (IL‐6), IL‐8, and tumor necrosis factor α. We demonstrated binding of C1q to PDCs both by surface plasmon resonance interaction analysis and by flow cytometry, and we also demonstrated intracellular detection of 2 C1q binding proteins.ConclusionOur findings contribute to the understanding of why C1q deficiency is such a strong risk factor for SLE and suggest an explanation for the up‐regulation of the type I IFN system seen in SLE patients.
Extreme obesity due to impaired leptin signaling in mice does not cause knee osteoarthritis
Authors: Griffin Timothy M. , Huebner Janet L. , Kraus Virginia B. , Guilak Farshid 
Published: September 2009

AbstractObjectiveTo test the hypothesis that obesity resulting from deletion of the leptin gene or the leptin receptor gene results in increased knee osteoarthritis (OA), systemic inflammation, and altered subchondral bone morphology.MethodsLeptin‐deficient (ob/ob) and leptin receptor–deficient (db/db) female mice compared with wild‐type mice were studied, to document knee OA via histopathology. The levels of serum proinflammatory and antiinflammatory cytokines were measured using a multiplex bead immunoassay. Cortical and trabecular subchondral bone changes were documented by microfocal computed tomography, and body composition was quantified by dual x‐ray absorptiometry.ResultsAdiposity was increased by ∼10‐fold in ob/ob and db/db mice compared with controls, but it was not associated with an increased incidence of knee OA. Serum cytokine levels were unchanged in ob/ob and db/db mice relative to controls, except for the level of cytokine‐induced neutrophil chemoattractant (keratinocyte chemoattractant; murine analog of interleukin‐8), which was elevated. Leptin impairment was associated with reduced subchondral bone thickness and increased relative trabecular bone volume in the tibial epiphysis.ConclusionExtreme obesity due to impaired leptin signaling induced alterations in subchondral bone morphology without increasing the incidence of knee OA. Systemic inflammatory cytokine levels remained largely unchanged in ob/ob and db/db mice. These findings suggest that body fat, in and of itself, may not be a risk factor for joint degeneration, because adiposity in the absence of leptin signaling is insufficient to induce systemic inflammation and knee OA in female C57BL/6J mice. These results imply a pleiotropic role of leptin in the development of OA by regulating both the skeletal and immune systems.
No increased occurrence of ischemic heart disease prior to the onset of rheumatoid arthritis: Results from two Swedish population‐based rheumatoid arthritis cohorts
Authors: Holmqvist Marie E. , Wedrén Sara , Jacobsson Lennart T. H. , Klareskog Lars , Nyberg Fredrik , Rantapää‐Dahlqvist Solbritt , Alfredsson Lars , Askling Johan 
Published: September 2009

AbstractObjectiveTo investigate the relative importance of shared etiologies for rheumatoid arthritis (RA) and ischemic heart disease (IHD) in terms of the well‐known increased risk of IHD in patients with RA, by assessing the occurrence of IHD up until the time of the onset of the first symptoms of RA.MethodsWe assessed the prevalence of a history of IHD, myocardial infarction (MI), and angina pectoris before the onset of RA symptoms in 2 large population‐based case–control studies. Patients with newly diagnosed RA according to the criteria of the American College of Rheumatology were included as cases. We used data from the Swedish Early Arthritis Register study and the Swedish Epidemiologic Investigation of Rheumatoid Arthritis case–control study and from general population controls. Information on IHD, MI, and angina pectoris was obtained from the nationwide Hospital Discharge Register and from self reports. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) to compare the prevalence of a history of IHD/MI/angina pectoris among patients with RA with that among population controls.ResultsWe could not detect any increased occurrence of IHD, MI, or angina pectoris before the onset of symptoms of RA, regardless of whether data on IHD were obtained from the Hospital Discharge Register or were self reported. As detected in the Hospital Discharge Register, the OR for IHD overall was 1.0 (95% CI 0.9–1.1), the OR for MI was 1.0 (95% CI 0.9–1.1), and the OR for angina pectoris was 1.0 (95% CI 0.9–1.2).ConclusionShared risk factors or susceptibilities for RA and IHD are likely to contribute less than RA‐related factors to the increased occurrence of IHD in patients with manifest RA. Nonetheless, the existence of shared factors associated with longer latency until the occurrence of IHD cannot be excluded.
Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage
Authors: Sui Yihong , Lee Jennifer H. , DiMicco Michael A. , Vanderploeg Eric J. , Blake Simon M. , Hung Han‐Hwa , Plaas Anna H. K. , James Ian E. , Song Xiao‐Yu , Lark Michael W. , Grodzinsky Alan J. 
Published: September 2009

AbstractObjectiveTraumatic joint injury can damage cartilage and release inflammatory cytokines from adjacent joint tissue. The present study was undertaken to study the combined effects of compression injury, tumor necrosis factor α (TNFα), and interleukin‐6 (IL‐6) and its soluble receptor (sIL‐6R) on immature bovine and adult human knee and ankle cartilage, using an in vitro model, and to test the hypothesis that endogenous IL‐6 plays a role in proteoglycan loss caused by a combination of injury and TNFα.MethodsInjured or uninjured cartilage disks were incubated with or without TNFα and/or IL‐6/sIL‐6R. Additional samples were preincubated with an IL‐6–blocking antibody Fab fragment and subjected to injury and TNFα treatment. Treatment effects were assessed by histologic analysis, measurement of glycosaminoglycan (GAG) loss, Western blot to determine proteoglycan degradation, zymography, radiolabeling to determine chondrocyte biosynthesis, and Western blot and enzyme‐linked immunosorbent assay to determine chondrocyte production of IL‐6.ResultsIn bovine cartilage samples, injury combined with TNFα and IL‐6/sIL‐6R exposure caused the most severe GAG loss. Findings in human knee and ankle cartilage were strikingly similar to those in bovine samples, although in human ankle tissue, the GAG loss was less severe than that observed in human knee tissue. Without exogenous IL‐6/sIL‐6R, injury plus TNFα exposure up‐regulated chondrocyte production of IL‐6, but incubation with the IL‐6–blocking Fab significantly reduced proteoglycan degradation.ConclusionOur findings indicate that mechanical injury potentiates the catabolic effects of TNFα and IL‐6/sIL‐6R in causing proteoglycan degradation in human and bovine cartilage. The temporal and spatial evolution of degradation suggests the importance of transport of biomolecules, which may be altered by overload injury. The catabolic effects of injury plus TNFα appeared partly due to endogenous IL‐6, since GAG loss was partially abrogated by an IL‐6–blocking Fab.
Scavenger receptor class A type I/II determines matrix metalloproteinase–mediated cartilage destruction and chondrocyte death in antigen‐induced arthritis
Authors: van Lent P. L. E. M. , Hofkens W. , Blom A. B. , Grevers L. , Sloetjes A. , Takahashi N. , van Tits L. J. , Vogl T. , Roth J. , de Winther M. P. , van den Berg W. B. 
Published: September 2009

AbstractObjectiveScavenger receptor class A type I (SR‐AI) and SR‐AII are expressed by macrophages in particular and bind and internalize a broad range of molecules (including endotoxins, apoptotic bodies, and oxidized low‐density lipoprotein). This study was undertaken to investigate the role of SR‐AI/II in mediating severe cartilage destruction in antigen‐induced arthritis (AIA).MethodsAIA was induced in the knee joints of SR‐AI/II−/− mice and wild‐type (WT) controls. Joint inflammation and cartilage destruction (chondrocyte death) were measured by examining the histology of total knee joints. Matrix metalloproteinase (MMP)–mediated neoepitopes were measured by immunolocalization using anti‐VDIPEN antibodies and chondrocyte activation with anti‐S100A8 antibodies. Messenger RNA (mRNA) levels were determined in inflamed synovium using microarray analysis and quantitative reverse transcriptase–polymerase chain reaction. In synovial washouts, cytokines (interleukin‐1β [IL‐1β], IL‐10, and tumor necrosis factor α) and S100A8/S100A9 were measured using Luminex and enzyme‐linked immunosorbent assay.ResultsLevels of SR‐AI/II mRNA were strongly elevated in inflamed synovium in AIA. On days 2, 8, and 14 after AIA induction, joint inflammation (exudates/infiltrate) was similar between the 2 groups. In WT mice, severe cartilage destruction was found in multiple cartilage surfaces of the inflamed knee joint on day 14 after AIA induction. MMP‐mediated matrix destruction ranged between 40% and 60%, and chondrocyte death was prominent in 40–75% of the cartilage surfaces. In striking contrast, in SR‐AI/II−/− mice, despite comparable joint inflammation, pronounced cartilage destruction was almost completely absent. Levels of IL‐1β and S100A8/S100A9 were significantly lower on days 7 and 14 after AIA induction, but levels of mRNA for various MMPs (MMP‐2, MMP‐3, MMP‐9, and MMP‐13) were comparable.ConclusionOur findings indicate that SR‐AI and SR‐AII are crucial receptors involved in mediating severe cartilage destruction in AIA.
Retinoid ameliorates experimental autoimmune myositis, with modulation of Th cell differentiation and antibody production in vivo
Authors: Ohyanagi Naho , Ishido Miwako , Suzuki Fumihito , Kaneko Kayoko , Kubota Tetsuo , Miyasaka Nobuyuki , Nanki Toshihiro 
Published: September 2009

AbstractObjectivePolymyositis and dermatomyositis are chronic inflammatory muscle diseases. Retinoids are compounds that bind to the retinoic acid binding site of retinoic acid receptors and have biologic activities similar to those of vitamin A. Recent studies indicate that retinoids promote Th2 differentiation and suppress Th1 and Th17 differentiation in vitro. The present study was undertaken to examine the effects of a synthetic retinoid, Am80, on experimental autoimmune myositis as well as on Th phenotype development and antibody production.MethodsExperimental autoimmune myositis was induced in SJL/J mice by immunization with rabbit myosin. Am80 was administered orally once daily. Its effects were evaluated by measurement of the numbers of infiltrating inflammatory cells, production of inflammatory cytokines in muscle, production of Th‐specific cytokines by myosin‐stimulated splenic T cells, and production of antimyosin antibodies in serum.ResultsIn mice with experimental autoimmune myositis, orally administered Am80 significantly reduced the number of infiltrating inflammatory cells and the expression of tumor necrosis factor α and interleukin‐1β (IL‐1β) in muscle. Moreover, Am80 increased production of interferon‐γ, IL‐4, and IL‐10, but not IL‐17, by myosin‐stimulated splenic T cells of mice with experimental autoimmune myositis, suggesting that it could enhance differentiation into Th1 and Th2, but not Th17, in vivo. Am80 also decreased serum levels of IgG2a and IgG2b antimyosin antibodies, but did not affect levels of IgG1 antimyosin antibodies. In addition, it suppressed chemokine expression and activator protein 1 activity in myoblasts in vitro.ConclusionThe synthetic retinoid Am80 has an inhibitory effect on experimental autoimmune myositis. It might regulate the development of Th phenotype and antibody production in vivo, in addition to its effects on cytokine and chemokine production.
Kippsicherheitsnachweis für Stahlbeton‐ und Spannbetonbinder
Authors: Hölter Dirk 
Published: September 2009

AbstractIn der Literatur finden sich verschiedene Normen und Richtlinien sowie verschiedene Theorien und Berechnungsansätze, um den Nachweis der Kippsicherheit für Binder führen zu können. Bei nahezu allen Veröffentlichungen ist für den Praktiker nicht auf einen Blick ersichtlich, ob überhaupt eine Untersuchung der Kippsicherheit erforderlich ist.Wenn die Kippsicherheit maßgeblich wird, gilt es zu beurteilen, welche Maßnahmen zum Erreichen der Kippsicherheit untersucht werden müssen. Hier soll der folgende Beitrag Transparenz schaffen.
Zur sinnvollen Anwendung ganzheitlicher Gebäudemodelle in der Tragwerksplanung von Hochbauten
Authors: Fastabend Michael , Schäfers Tobias , Albert Mark , Lommen Hans‐Gerd 
Published: September 2009

AbstractAusgehend von den kritischen Randbedingungen der Berechnung mit ganzheitlichen Gebäudemodellen werden typische und häufig anzutreffende Konstruktionsfälle diskutiert, bei denen Gesamtmodelle Vorteile für den Entwurf aufzeigen. Hier sind räumliche Tragwirkungen zu nennen, die Erfassung von Zwangsbeanspruchungen bei komplexen Grundrissen mit vielfältigen Festhaltungen sowie die Beanspruchung schlanker Gebäudestrukturen aus Windlasten und seismischen Einwirkungen. Für die genannten sinnvollen Anwendungsfälle werden die notwendigen Randbedingungen diskutiert. Die jeweiligen Anwendungsfälle werden anhand konkreter Gebäudebeispiele vorgestellt.On the reasonable use of total building models in the design of building structuresComing from the critical boundary conditions of the calculation with total building models, typical and prevalent constructions, where total models show advantages for the design, will be discussed. Here, spatial load‐bearing impact, the registration of unforced interactions of complex ground plans with various supports as well as the stressing of slender building structures resulting from wind loads and seismic impacts have to be mentioned. For the stated reasonable use cases the necessary boundary conditions will be discussed. The respective use cases will be presented by means of concrete building examples.
Vergleich statischer und dynamischer Methoden zur Zustandsbewertung von Stahlbeton‐ und Spannbetontragwerken
Authors: Waltering Markus , Bungard Volker , Waldmann Danièle , Maas Stefan , Zürbes Arno 
Published: September 2009

AbstractRisse in Stahlbeton‐ und Spannbetontragwerken führen zu einem Steifigkeitsverlust, der die statischen und dynamischen Eigenschaften der jeweiligen Struktur beeinflusst. Eine klassische Methode zur Bestimmung statischer Kennwerte sind Probebelastungen, bei denen gemessene Verformungen mit rechnerischen Werten abgeglichen werden und somit einen Rückschluss auf die Tragfähigkeit der Struktur ermöglichen. Bei Bauwerken wie Brücken können derartige Tests sehr kosten‐, zeit‐ und materialaufwändig sein und erfordern häufig eine längerfristige Sperrung. Des Weiteren müssen die gemessenen Verformungen vor Ort durch erfahrene Ingenieure überwacht werden, um gegebenenfalls bei Überschreiten kritischer Werte den Test abzubrechen. Auch die dynamischen Eigenschaften von Strukturen werden maßgeblich durch die Steifigkeit beeinflusst und können in vielen Fällen schnell und mit wenig Aufwand bestimmt werden. Im Rahmen dieses Aufsatzes werden die Ergebnisse statischer und dynamischer Untersuchungen zur Zustandsbewertung, durchgeführt an Stahlbeton‐ und Spannbetonbauteilen im Labor und an einer schrittweise geschädigten Spannbetonbrücke, hinsichtlich ihrer Sensibilität auf Schäden und Handhabbarkeit in der praktischen Anwendung gegenübergestellt.Comparison of Static and Dynamic Methods to Assess the State of Reinforced and Prestressed Concrete StructuresCracks in reinforced and prestressed concrete structures lead to a reduction in stiffness and therefore to an influence on the static and dynamic properties. A conventional method to assess the static characteristics are static load tests which enable to correlate measured deformations with calculated values and to draw conclusions about the loading capacity. In case of bridges, these tests can be very cost‐intensive and time‐consuming and often require a closure of the bridge. Furthermore the measured deformations have to be examined in situ, in order to abort the test if the deformations exceed critical values. As well, the dynamic properties are affected by changes in stiffness and in many cases they can be quickly determined without large effort. Within this article the results of static and dynamic tests with laboratory reinforced and prestressed concrete structures and tests on a gradually damaged prestressed concrete bridge are presented. The results are compared with regard to the sensitivity of the different methods to damage.
Hochleistungsleichtbeton unter mehraxialer Druckbeanspruchung
Authors: Scheerer Silke , Hampel Torsten , Curbach Manfred 
Published: September 2009

AbstractAn vielen Stellen im Tragwerk herrschen mehraxiale Spannungszustände. Ob sich die Tragfähigkeit von Hochleistungsleichtbetonen unter mehraxialer Druckbeanspruchung ebenso erhöht wie bei Normalbetonen, wurde in zwei‐ und dreiaxialen Tests untersucht. Es wurde ein Bruchkriterium für Leichtbetone abgeleitet und Parallelen und Unterschiede zu Normalbeton aufgezeigt.High Performance Lightweight Aggregate Concrete under Multiaxial CompressionThere are multiaxial stress conditions at many points in a structure. Whether the strength of high performance lightweight concrete under multiaxial compression increases as well as the strength of normal concrete, was verified in bi‐ and triaxial tests. A failure criterion for lightweight concrete was derived and analogies and differences to normal oncrete were pointed out.
Querkrafttragfähigkeit von Fahrbahnplatten ohne Querkraftbewehrung
Authors: Rombach Günter , Latte Sören 
Published: September 2009

AbstractEs wird über Versuche zur Querkrafttragfähigkeit von Brückenfahrbahnplatten aus Stahlbeton berichtet. Diese zeigen, dass die bekannten Rechenansätze für Bauteile ohne Querkraftbewehrung nach DIN 1045‐1 bzw. DIN‐FB 102 für Fahrbahnplatten auf der sicheren Seite liegen, die tatsächliche Tragfähigkeit aber weit unterschätzt wird. Weitere Ansätze zur Berechnung der Querkrafttragfähigkeit von Stahlbetonbauteilen ohne Querkraftbewehrung werden erörtert. Während die Modelle bei der Auswertung einer Datenbank von Balkenversuchen eine gute Übereinstimmung aufweisen, zeigt der Vergleich mit den Modellversuchen, dass die meisten Rechenverfahren die Tragfähigkeit der Platten unterschätzen. Zur Berechnung der Querkrafttragfähigkeit von Platten ohne Querkraftbewehrung unter Punktlasten wird ein Modell vorgeschlagen, welches die Querkrafttragfähigkeit mit der Zugbeanspruchung der Biegezugzone im kritischen Bereich verknüpft.Shear Resistance of Bridge Decks without Transverse ReinforcementThe design of concrete bridge deck slabs is of major concern since the introduction of the Eurocodes as the calculated shear capacity of slabs without stirrups and staggered reinforcement according to the new design standards is often considerably smaller compared to the former regulations i.e. DIN 1045:88. This raises the question whether the existing structures are still save. A series of 12 tests on 4 different specimens representing a bridge deck was performed to examine the real load bearing behaviour of a slab with and without shear reinforcement under a wheel (point) load. The evaluation of the test results revealed, that the current design formula with an assumed elastic shear force distribution leads to rather conservative values of shear capacity for bridge deck slabs. Various approaches for shear design are discussed and the accuracy is checked by means of a shear database and the test results. A new model to calculate the shear capacity is proposed which shows a better agreement with test data than the known approaches.