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Sprifermin (rhFGF18) enables proliferation of chondrocytes producing a hyaline cartilage matrix
(2017)
Objective: Fibroblast growth factor (FGF) 18 has been shown to increase cartilage volume when injected intra-articularly in animal models of osteoarthritis (OA) and in patients with knee OA (during clinical development of the recombinant human FGF18, sprifermin). However, the exact nature of this effect is still unknown. In this study, we aimed to investigate the effects of sprifermin at the cellular level.
Design: A combination of different chondrocyte culture systems was used and the effects of sprifermin on proliferation, the phenotype and matrix production were evaluated. The involvement of MAPKs in sprifermin signalling was also studied.
Results: In monolayer, we observed that sprifermin promoted a round cell morphology and stimulated both cellular proliferation and Sox9 expression while strongly decreasing type I collagen expression. In 3D culture, sprifermin increased the number of matrix-producing chondrocytes, improved the type II:I collagen ratio and enabled human OA chondrocytes to produce a hyaline extracellular matrix (ECM). Furthermore, we found that sprifermin displayed a ‘hit and run’ mode of action, with intermittent exposure required for the compound to fully exert its anabolic effect. Finally, sprifermin appeared to signal through activation of ERK.
Conclusions: Our results indicate that intermittent exposure to sprifermin leads to expansion of hyaline cartilage-producing chondrocytes. These in vitro findings are consistent with the increased cartilage volume observed in the knees of OA patients after intra-articular injection with sprifermin in clinical studies.
Using CORSIKA for simulating extensive air showers, we study the relation between the shower characteristics and features of hadronic multiparticle production at low energies. We report about investigations of typical energies and phase space regions of secondary particles which are important for muon production in extensive air showers. Possibilities to measure relevant quantities of hadron production in existing and planned accelerator experiments are discussed.
Electric charge correlations were studied for p+p, C+C, Si+Si, and centrality selected Pb+Pb collisions at sqrt[sNN]=17.2 GeV with the NA49 large acceptance detector at the CERN SPS. In particular, long-range pseudorapidity correlations of oppositely charged particles were measured using the balance function method. The width of the balance function decreases with increasing system size and centrality of the reactions. This decrease could be related to an increasing delay of hadronization in central Pb+Pb collisions.
Particle production in central Pb+Pb collisions was studied with the NA49 large acceptance spectrometer at the CERN SPS at beam energies of 20, 30, 40, 80, and 158 GeV per nucleon. A change of the energy dependence is observed around 30A GeV for the yields of pions and strange particles as well as for the shapes of the transverse mass spectra. At present only a reaction scenario with onset of deconfinement is able to reproduce the measurements.
System-size dependence of strangeness production in nucleus-nucleus collisions at √sNN = 17.3 GeV
(2005)
Emission of pi, K, phi and Lambda was measured in near-central C+C and Si+Si collisions at 158 AGeV beam energy. Together with earlier data for p+p, S+S and Pb+Pb, the system-size dependence of relative strangeness production in nucleus-nucleus collisions is obtained. Its fast rise and the saturation observed at about 60 participating nucleons can be understood as onset of the formation of coherent partonic subsystems of increasing size. PACS numbers: 25.75.-q
Vortrag gehalten am 12. Januar 2005 in Frankfurt am Main, am Physikalischen Verein, anläßlich der Verleihung des Philipp-Siedler-Wissenschaftspreises an Dipl.-Phys. Christine Meurer, als Anerkennung für ihre Diplomarbeit "Xi- und Xi+ Produktion in Pb+Pb Stößen bei 40 A GeV am CERN SPS" (urn:nbn:de:hebis:30-13740). Am CERN, dem Europäischen Kernforschungszentrum, werden Bleiatomkerne auf nahezu Lichtgeschwindigkeit beschleunigt und zur Kollision gebracht. Dabei wird die Materie in einer Art Feuerball extrem verdichtet und erhitzt. Unter diesen Bedingungen brechen die Bestandteile der Atomkerne, die Nukleonen, auf und der Blick auf die eigentlichen Bausteine der Materie, die Quarks, wird möglich. Nach der Kollision expandiert der Feuerball und viele neue Teilchen, darunter auch die sogenannten seltsamen Teilchen, entstehen. Ihre Besonderheiten werden im Vortrag diskutiert: Ergebnisse zur Produktion des seltsamen Xi- -Teilchens in Pb+Pb-Stößen bei einer Energie von 40 A GeV werden vorgestellt. Aus dem transversalen Massenspektrum bei mittlerer Rapidität erhält man einen inversen Steigungsparamenter von T Xi- = (210±11±21)MeV . Die Integration des Rapiditätsspektrums liefert eine totale Anzahl der s im gesamten Phasenraum von (2.41 ± 0.15 ± 0.24) Teilchen pro Kollision. Desweiteren wird die Anregungsfunktion des Xi- -Hyperons sowie seine Zentralitätsabhänigkeit bei 40 A GeV diskutiert.
Results are presented on Omega production in central Pb+Pb collisions at 40 and 158 AGeV beam energy. Given are transverse-mass spectra, rapidity distributions, and total yields for the sum Omega+Antiomega at 40 AGeV and for Omega and Antiomega separately at 158 AGeV. The yields are strongly under-predicted by the string-hadronic UrQMD model and are in better agreement with predictions from a hadron gas models. PACS numbers: 25.75.Dw
Evidence for an exotic S=-2, Q=-2 baryon resonance in proton-proton collisions at the CERN SPS
(2004)
Results of resonance searches in the Xi - pi -, Xi - pi +, Xi -bar+ pi -, and Xi -bar+ pi + invariant mass spectra in proton-proton collisions at sqrt[s]=17.2 GeV are presented. Evidence is shown for the existence of a narrow Xi - pi - baryon resonance with mass of 1.862±0.002 GeV/c2 and width below the detector resolution of about 0.018 GeV/c2. The significance is estimated to be above 4.2 sigma . This state is a candidate for the hypothetical exotic Xi --3/2 baryon with S=-2, I=3 / 2, and a quark content of (dsdsu-bar). At the same mass, a peak is observed in the Xi - pi + spectrum which is a candidate for the Xi 03/2 member of this isospin quartet with a quark content of (dsusd-bar). The corresponding antibaryon spectra also show enhancements at the same invariant mass.
Results are presented on event-by-event electric charge fluctuations in central Pb+Pb collisions at 20, 30, 40, 80 and 158 AGeV. The observed fluctuations are close to those expected for a gas of pions correlated by global charge conservation only. These fluctuations are considerably larger than those calculated for an ideal gas of deconfined quarks and gluons. The present measurements do not necessarily exclude reduced fluctuations from a quark-gluon plasma because these might be masked by contributions from resonance decays.
Production of Lambda and Antilambda hyperons was measured in central Pb-Pb collisions at 40, 80, and 158 A GeV beam energy on a fixed target. Transverse mass spectra and rapidity distributions are given for all three energies. The Lambda/pi ratio at mid-rapidity and in full phase space shows a pronounced maximum between the highest AGS and 40 A GeV SPS energies, whereas the anti-Lambda}/pi ratio exhibits a monotonic increase. PACS numbers: 25.75.-q