TY - THES A1 - Munkert, Tobias T1 - Knochenmarker bei Osteoporose und Analyse von Serumparametern T1 - Bone markers in osteoporosis and analysis of serum parameters N2 - Die Diagnose der Osteoporose stützt sich auch heute noch auf die radiologische Messung der Knochendichte (National Institutes of Health, 2000, National Osteoporosis Foundation, 2013, Dachverband Osteologie e. V., 2009a). Seine klinische Wertigkeit erreicht aber auch dieses Verfahren nur in gemeinsamer Betrachtung mit anderen klinischen Risikofaktoren. Mit dieser Methode ist es möglich Frakturrisiken abzuschätzen, die aktuelle Knochendichte zu bestimmen und Therapieverläufe zu dokumentieren. Radiologisch werden diese Veränderungen jedoch erst nach 12 bis 24 Monaten sichtbar (Delmas et al., 2000). Ein wichtiges Ergebnis dieser Arbeit ist die Bestätigung der Tatsache, dass ein relevanter Anteil von Frakturen sich bereits bei PatientInnen mit Osteopenie oder sogar mit normaler Knochendichte ereignet, was sowohl für Frauen als auch für Männer gilt. Pathologische Knochendichteveränderungen finden sich jedoch nicht nur bei Osteoporose, sondern auch bei Erkrankungen wie beispielsweise Hyper- und Hypoparathyreoidismus, Hypophosphatasie, TIO, Rachitis und Morbus Paget. Ziel dieser Arbeit war zunächst die Erstellung einer Datenbank aus vorliegenden Serumproben und die Analyse statistischer Zusammenhänge zwischen den ermittelten Parametern. Es konnten für Osteoporosen typische signifikante Zusammenhänge zwischen dem Alter und den T-Werten an Wirbelsäule und Hüfte ermittelt werden. Durch veränderte PTH-, AP- und 25(OH)-Vitamin D3-Konzentrationen kann erhöhter Knochenumbau erkannt werden (Jakob, 2007). In dieser Arbeit errechnete signifikante Zusammenhänge wie beispielsweise zwischen AP und NTx deuten auf erhöhten Knochenumbau hin, wodurch Rückschlüsse auf Erkrankungen wie beispielsweise Morbus Paget oder Knochenmetastasen gezogen werden können. Diese und andere Ergebnisse dieser Arbeit erscheinen für das Kollektiv einer osteoporotischen Spezialsprechstunde schlüssig. Der hier ermittelte Prozentsatz pathologischer Laborwerte im Gesamtkollektiv beweist auch, dass es sinnvoll und ökonomisch ist, bei entsprechend osteologischer Fragestellung die betreffenden Parameter zu untersuchen, da sich sehr häufig relevante differentialdiagnostische Fragestellungen ergeben. In weiterführenden Untersuchungen soll auf diese Datenbank zurückgegriffen und Serumkollektive extrahiert bzw. analysiert werden. Diese können anschließend für genauere Untersuchungen (ELISA) auf weitere Parameter verwendet werden, um Zusammenhänge zwischen knochenrelevanten Parametern und Knochenerkrankungen darzustellen. Um dies jedoch zu belegen, sind zusätzliche Untersuchungen mit weiteren Knochenmarkern wie OC, CTX, BAP in ähnlichen Kollektiven nötig. Es sollten hierfür zudem Serumproben und Knochendichtemessungen über längere Zeiträume (idealerweise zehn Jahre) analysiert werden, um möglichst genaue Ergebnisse zu erhalten und um mögliche Fremdeinflüsse erkennen zu können (Delmas et al., 2000). Zukünftig wäre es mit dieser Methode möglich, frühzeitig sensitives Risikoassessment zu betreiben, pathologische Knochenveränderungen und deren Ursachen zu diagnostizieren und vor Auftreten klinischer Symptome gezielt präventive Therapiemaßnahmen einzuleiten. N2 - The diagnosis of osteoporosis disease is currently still based on radiological measurement of the bone density. The clinical significance of this method is limited by the joint analysis of additional clinical risk factors. By using this method it is forthwith possible to evaluate the risks of bone fractures, the current bone density and to document the progress of therapies, whereas changes in bone density are for the first time identifiable after 12-24 month with radiographic methodes. The priority of this research study was to create a database out of serum samples and to analyse the statistic coherences, followed by the interpretation of the results and the establishment of the differential diagnosis. One important result was the confirmation of the fact that a relevant part of bone fractures occured at patients with osteopenia or normal bone density, affecting both men and women. Indeed, pathologic aberrations of bone densities are linked with osteoporosis and also other diseases like hyper- and hypoparathereoidism, hypophosphatasia, TIO, rachitis and Paget’s disease. In further studies this database should be used to extract or rather analyse special collectives. Subsequently, these can be used as starting points for detailed immunological studies (e.g. ELISA) to illustrate relations between bone-relevant parameters and bone diseases and to identify changes in bone mineral density at a very early stage by developing new bone markers. KW - Osteoporose KW - Knochenmarker KW - Osteoporose Serumparameter Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-155168 ER - TY - THES A1 - Massig, Felix T1 - Vergleich verschiedener Operationsverfahren der Patellarückfläche bei Knieprothesenwechsel T1 - Comparison of different treatments of the Patella at the time of Knee Revision Arthroplasty N2 - Die Arthrose des Kniegelenkes stellt heutzutage die häufigste Gelenkerkrankung des Menschen dar. Nachdem die konservativen Therapiemöglichkeiten ausgeschöpft sind, wird dem Patienten meist die Implantation einer Knietotalendoprothese empfohlen. Aufgrund von Schmerzen, einer Infektion, oder einer Lockerung der Prothese kann jedoch ein Wechsel des Gelenkersatzes notwendig werden. Das Femoropatellargelenk stellt bei solchen Revisionsoperationen das häufigste und bedeutendste Problem dar. Diese Studie vergleicht 5 operative Verfahren der Patella-rückflächenbearbeitung bei Revisionsoperationen. Hierzu wurden 118 Patienten anhand von 6 etablierten Scores sowie klinisch und radiologisch nach durchschnittlich ca. 2 Jahren nachuntersucht. Die Gruppe der Patienten, welche vor der Revisionsoperation eine ersetzte Patellarückfläche aufwiesen und bei welchen dieser Ersatz entnommen und somit ein knöcherner Rest hinterlassen wurde, zeigte in fast allen Scores deutliche, wenn auch nicht signifikant schlechtere Ergebnisse. Diese gliedern sich gut in die Arbeiten anderer Autoren zu diesem Thema ein. Weiterhin zeigte sich, dass der Kniescore nach Turba et al. für die Evaluation des Femoropatellargelenkes bei Knieprothesenrevisionen ungeeignet ist. Bei der Patellarückflächenbearbeitung während Revisionsoperationen sollte beim Hinweis auf eine Beschädigung der Patellakomponente diese gewechselt werden, ansonsten kann der bestehende Ersatz belassen werden. Das Entfernen eines bestehenden Ersatzes mit Hinterlassen eines knöchernen Restes sollte vermieden werden. Bei weiteren Studien zu diesem Thema wäre es wünschenswert, zusätzlich zur postoperativen Untersuchung eine präoperative Untersuchung durchzuführen. Die Ergebnisse dieser Arbeit wurden auf dem SICOT-Weltkongress der Orthopäden 2013 vorgestellt. N2 - Comparison of different treatments of the Patella at the time of Knee Revision Arthroplasty KW - Patella KW - Kniegelenkprothese KW - Revision KW - Knee KW - Resurface Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143434 ER - TY - JOUR A1 - Jessberger, Steffen A1 - Högger, Petra A1 - Genest, Franca A1 - Salter, Donald M. A1 - Seefried, Lothar T1 - Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study JF - BMC Complementary and Alternative Medicine N2 - Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA. KW - maritime pine bark extract KW - qPCR KW - ADAMTS KW - cartilage KW - clinical study KW - osteoarthritis KW - Pycnogenol KW - serum KW - synovial fluid Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-159532 VL - 17 IS - 537 ER - TY - JOUR A1 - Krstic, Jelena A1 - Herrmann, Marietta A1 - Gadjanski, Ivana A1 - Mojsilovic, Slavko T1 - Editorial: Microenvironment-derived stem cell plasticity JF - Frontiers in Cell and Developmental Biology N2 - No abstract available. KW - plasticity KW - stem cells KW - microenvironment KW - imaging KW - extracellular vesicles (EVs) KW - oxygen tension KW - tissue regeneration KW - immunomodulation Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197424 SN - 2296-634X VL - 5 ER - TY - JOUR A1 - Arnholdt, Jörg A1 - Gilbert, Fabian A1 - Blank, Marc A1 - Papazoglou, Jannis A1 - Rudert, Maximilian A1 - Nöth, Ulrich A1 - Steinert, Andre F. T1 - The Mayo conservative hip: complication analysis and management of the first 41 cases performed at a University level 1 department JF - BMC Muskoskeletal Disorders N2 - Background: To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems. Methods: In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months. Results: The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases. Conclusion: In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort." KW - total hip arthroplasty KW - short hip stem KW - mayo stem KW - minimal invasive surgery Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-157812 VL - 18 IS - 250 ER - TY - JOUR A1 - Armbruster, Nicole A1 - Krieg, Jennifer A1 - Weißenberger, Manuel A1 - Scheller, Carsten A1 - Steinert, Andre F. T1 - Rescued Chondrogenesis of Mesenchymal Stem Cells under Interleukin 1 Challenge by Foamyviral Interleukin 1 Receptor Antagonist Gene Transfer JF - Frontiers in Pharmacology N2 - Background: Mesenchymal stem cells (MSCs) and their chondrogenic differentiation have been extensively investigated in vitro as MSCs provide an attractive source besides chondrocytes for cartilage repair therapies. Here we established prototype foamyviral vectors (FVV) that are derived from apathogenic parent viruses and are characterized by a broad host range and a favorable integration pattern into the cellular genome. As the inflammatory cytokine interleukin 1 beta (IL1β) is frequently present in diseased joints, the protective effects of FVV expressing the human interleukin 1 receptor antagonist protein (IL1RA) were studied in an established in vitro model (aggregate culture system) of chondrogenesis in the presence of IL1β. Materials and Methods: We generated different recombinant FVVs encoding enhanced green fluorescent protein (EGFP) or IL1RA and examined their transduction efficiencies and transgene expression profiles using different cell lines and human primary MSCs derived from bone marrow-aspirates. Transgene expression was evaluated by fluorescence microscopy (EGFP), flow cytometry (EGFP), and ELISA (IL1RA). For evaluation of the functionality of the IL1RA transgene to block the inhibitory effects of IL1β on chondrogenesis of primary MSCs and an immortalized MSC cell line (TERT4 cells), the cells were maintained following transduction as aggregate cultures in standard chondrogenic media in the presence or absence of IL1β. After 3 weeks of culture, pellets were harvested and analyzed by histology and immunohistochemistry for chondrogenic phenotypes. Results: The different FVV efficiently transduced cell lines as well as primary MSCs, thereby reaching high transgene expression levels in 6-well plates with levels of around 100 ng/ml IL1RA. MSC aggregate cultures which were maintained in chondrogenic media without IL1β supplementation revealed a chondrogenic phenotype by means of strong positive staining for collagen type II and matrix proteoglycan (Alcian blue). Addition of IL1β was inhibitory to chondrogenesis in untreated control pellets. In contrast, foamyviral mediated IL1RA expression rescued the chondrogenesis in pellets cultured in the presence of IL1β. Transduced MSC pellets reached thereby very high IL1RA transgene expression levels with a peak of 1087 ng/ml after day 7, followed by a decrease to 194 ng/ml after day 21, while IL1RA concentrations of controls were permanently below 200 pg/ml. Conclusion: Our results indicate that FVV are capable of efficient gene transfer to MSCs, while reaching IL1RA transgene expression levels, that were able to efficiently block the impacts of IL1β in vitro. FVV merit further investigation as a means to study the potential as a gene transfer tool for MSC based therapies for cartilage repair. KW - mesenchymal stem cell KW - chondrogenesis KW - pellet culture KW - foamy virus KW - virus vectors KW - IL1RA KW - interleukin 1 receptor antagonist KW - arthritis Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170919 VL - 8 IS - 255 ER - TY - JOUR A1 - Müller-Deubert, Sigrid A1 - Seefried, Lothar A1 - Krug, Melanie A1 - Jakob, Franz A1 - Ebert, Regina T1 - Epidermal growth factor as a mechanosensitizer in human bone marrow stromal cells JF - Stem Cell Research N2 - Epidermal growth factors (EGFs) e.g. EGF, heparin-binding EGF and transforming growth factor alpha and their receptors e.g. EGFR and ErbB2 control proinflammatory signaling and modulate proliferation in bone marrow stromal cells (BMSC). Interleukin-6 and interleukin-8 are EGF targets and participate in the inflammatory phase of bone regeneration via non-canonical wnt signaling. BMSC differentiation is also influenced by mechanical strain-related activation of ERK1/2 and AP-1, but the role of EGFR signaling in mechanotransduction is unclear. We investigated the effects of EGFR signaling in telomerase-immortalized BMSC, transfected with a luciferase reporter, comprising a mechanoresponsive AP1 element, using ligands, neutralizing antibodies and EGFR inhibitors on mechanotransduction and we found that EGF via EGFR increased the response to mechanical strain. Results were confirmed by qPCR analysis of mechanoresponsive genes. EGF-responsive interleukin-6 and interleukin-8 were synergistically enhanced by EGF stimulation and mechanical strain. We show here in immortalized and primary BMSC that EGFR signaling enhances mechanotransduction, indicating that the EGF system is a mechanosensitizer in BMSC. Alterations in mechanosensitivity and -adaptation are contributors to age-related diseases like osteoporosis and the identification of a suitable mechanosensitizer could be beneficial. The role of the synergism of these signaling cascades in physiology and disease remains to be unraveled. KW - mechanotransduction KW - bone marrow stromal cells KW - epidermal growth factor KW - signaling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170247 VL - 24 ER -