@article{KamawalSteinertHolzapfeletal.2016,
  author    = {Kamawal, Yama and Steinert, Andre F and Holzapfel, Boris M and Rudert, Maximilian and Barthel, Thomas},
  title     = {Case report - calcification of the medial collateral ligament of the knee with simultaneous calcifying tendinitis of the rotator cuff},
  series = {BMC Muscoskeletal Disorders},
  volume    = {17},
  journal   = {BMC Muscoskeletal Disorders},
  number    = {283},
  doi       = {10.1186/s12891-016-1147-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147669},
  year      = {2016},
  abstract  = {Calcification of the medial collateral ligament (MCL) of the knee is a very rare disease. We report on a case of a patient with a calcifying lesion within the MCL and simultaneous calcifying tendinitis of the rotator cuff in both shoulders. Case presentation: Calcification of the MCL was diagnosed both via x-ray and magnetic resonance imaging (MRI) and was successfully treated surgically. Calcifying tendinitis of the rotator cuff was successfully treated applying conservative methods. Conclusion: This is the first case report of a patient suffering from both a calcifying lesion within the medial collateral ligament and calcifying tendinitis of the rotator cuff in both shoulders. Clinical symptoms, radio-morphological characteristics and macroscopic features were very similar and therefore it can be postulated that the underlying pathophysiology is the same in both diseases. Our experience suggests that magnetic resonance imaging and x-ray are invaluable tools for the diagnosis of this inflammatory calcifying disease of the ligament, and that surgical repair provides a good outcome if conservative treatment fails. It seems that calcification of the MCL is more likely to require surgery than calcifying tendinitis of the rotator cuff. However, the exact reason for this remains unclear to date.},
  language  = {en}
}
@article{DotterweichSchlegelmilchKelleretal.2016,
  author    = {Dotterweich, Julia and Schlegelmilch, Katrin and Keller, Alexander and Geyer, Beate and Schneider, Doris and Zeck, Sabine and Tower, Robert J. J. and Ebert, Regina and Jakob, Franz and Sch{\"u}tze, Norbert},
  title     = {Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease},
  series = {Bone},
  volume    = {93},
  journal   = {Bone},
  doi       = {10.1016/j.bone.2016.08.006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186688},
  pages     = {155-166},
  year      = {2016},
  abstract  = {Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.},
  language  = {en}
}
@phdthesis{Schmalzl2016,
  author    = {Schmalzl, Jonas Georg},
  title     = {Genetische Modifikation humaner mesenchymaler Stammzellen zur Stimulation der Knochenheilung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142391},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Fragestellung: Die Therapie von Knochendefekten kritischer Gr{\"o}ße mit kompromittiertem Regenerationspotential, stellt ein schwerwiegendes Problem dar. Die Forschung auf dem Gebiet der Knochenheilung hat sich in j{\"u}ngster Vergangenheit daher auf die Anwendung mesenchymaler Vorl{\"a}uferzellen (MSZ) zur Stimulierung des Knochenwachstums konzentriert. In der vorliegenden Studie wurde in humanen MSZ eine {\"U}berexpression spezifischer Wachstumsfaktoren induziert mit dem Ziel, deren osteogenes Potential zu steigern. Methodik: MSZ wurden nach etablierten Protokollen expandiert. Durch adenovirale Transfektion wurde eine {\"u}berexpression von gr{\"u}n fluoreszierendem Protein (GFP, Kontrolle), indian hedgehog (IHH), bone morphogenetic protein 2 (BMP-2) und IHH in Kombination mit BMP-2 induziert. Die MSZ wurden f{\"u}r 28 Tage mit osteogenem Differenzierungs- und Kontrollmedium kultiviert. Als weitere Kontrolle dienten native MSZ. Es wurden die Auswirkungen der jeweiligen genetischen Ver{\"a}nderungen auf die metabolische Aktivit{\"a}t (Alamar Blau), die Proliferation (Qubit dsDNA BR), die Aktivit{\"a}t des Enzyms alkalische Phosphatase (ALP)(p-Nitrophenylphosphat), die Mineralisierung (Alizarinrot S, Calcium O-Cresolphthalein) sowie auf die Expression charakteristischer Markergene untersucht (qRT-PCR). Ergebnis: In den ersten 72h nach Transfektion konnte eine leichte, im Vergleich zu nativen Zellen nicht signifikante Abnahme der metabolischen Aktivit{\"a}t in allen Gruppen beobachtet werden. Das Proliferationsverhalten transfizierter und nativer MSZ unterschied sich w{\"a}hrend des Untersuchungszeitraums nicht signifikant. Bei der Analyse der ALP-Aktivit{\"a}t zeigte sich ein typisches Rise-and-Fall Muster. Alle ost Gruppen wiesen sowohl im Assay als auch in der PCR eine signifikant h{\"o}here ALP-Aktivit{\"a}t auf. Die {\"U}berexpression von BMP-2 und IHH+BMP-2 bewirkte eine signifikant st{\"a}rkere Mineralisierung an Tag 28. In der PCR zeigte sich f{\"u}r BMP-2 ost und IHH+BMP2 ost ein signifikanter Anstieg der Osteopontin und BMP-2 Expression {\"u}ber die Zeit. Zudem stieg bei allen ost Gruppen die Runx2 Expression bis Tag 21 an. Schlussfolgerung: Die virale Transfektion hatte keinen negativen Einfluss auf die metabolische Aktivit{\"a}t der Zellen oder deren Proliferationsverhalten. Die {\"U}berexpression von BMP-2 ohne oder in Kombination mit IHH f{\"u}hrte zu einer vermehrten Produktion extrazellul{\"a}rer Matrix und zu einer gesteigerten Genexpression osteogener Marker. Die virale Transfektion stellt daher eine vielversprechende M{\"o}glichkeit dar, das osteogene Potential von MSZ zu steigern.},
  subject      = {Stammzellen},
  language  = {de}
}
@article{WittmannSiebervonStengeletal.2016,
  author    = {Wittmann, Katharina and Sieber, Cornel and von Stengel, Simon and Kohl, Matthias and Freiberger, Ellen and Jakob, Franz and Lell, Michael and Engelke, Klaus and Kemmler, Wolfgang},
  title     = {Impact of whole body electromyostimulation on cardiometabolic risk factors in older women with sarcopenic obesity: the randomized controlled FORMOsA-sarcopenic obesity study},
  series = {Clinical Interventions in Aging},
  volume    = {11},
  journal   = {Clinical Interventions in Aging},
  doi       = {10.2147/CIA.S116430},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164930},
  pages     = {1697—1706},
  year      = {2016},
  abstract  = {Background: Sarcopenic obesity (SO) is characterized by a combination of low muscle and high fat mass with an additive negative effect of both conditions on cardiometabolic risk. The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on the metabolic syndrome (MetS) in community-dwelling women aged ≥70 years with SO. Methods: The study was conducted in an ambulatory university setting. Seventy-five community-dwelling women aged ≥70 years with SO living in Northern Bavaria, Germany, were randomly allocated to either 6 months of WB-EMS application with (WB-EMS\&P) or without (WB-EMS) dietary supplementation (150 kcal/day, 56\% protein) or a non-training control group (CG). WB-EMS included one session of 20 min (85 Hz, 350 µs, 4 s of strain-4 s of rest) per week with moderate-to-high intensity. The primary study endpoint was the MetS Z-score with the components waist circumference (WC), mean arterial pressure (MAP), triglycerides, fasting plasma glucose, and high-density lipoprotein cholesterol (HDL-C); secondary study endpoints were changes in these determining variables. Results: MetS Z-score decreased in both groups; however, changes compared with the CG were significant (P=0.001) in the WB-EMS\&P group only. On analyzing the components of the MetS, significant positive effects for both WB-EMS groups (P≤0.038) were identified for MAP, while the WB-EMS group significantly differed for WC (P=0.036), and the WB-EMS\&P group significantly differed for HDL-C (P=0.006) from the CG. No significant differences were observed between the WB-EMS groups. Conclusion: The study clearly confirms the favorable effect of WB-EMS application on the MetS in community-dwelling women aged ≥70 years with SO. However, protein-enriched supplements did not increase effects of WB-EMS alone. In summary, we considered this novel technology an effective and safe method to prevent cardiometabolic risk factors and diseases in older women unable or unwilling to exercise conventionally.},
  language  = {en}
}
@phdthesis{Kraetzig2016,
  author    = {Kr{\"a}tzig, Theresa},
  title     = {Pilotstudie zum Vergleich der Knorpelrekonstruktion durch Autologe Chondrozytentransplantation und Autologe Stammzelltransplantation in Kollagen I Hydrogelen am G{\"o}ttinger Mini-Pig},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-138822},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Traumatische und/oder degenerative, umschriebene Knorpeldefekte sind aufgrund der schlechten intrinsischen Regenerationseigenschaften des Knorpelgewebes immer noch eine chirurgische Herausforderung. Therapiem{\"o}glichkeiten mittels Knorpelrekonstruktion durch autologes Knorpelgewebe hat den Nachteil der „donor-site-morbidity" und auch die mit guten klinischen und bildmorphologischen Ergebnissen bereits in der Klinik angewandte matrixgekoppelte autologe Chondrozytentransplantation kommt nicht ohne eine zus{\"a}tzliche Operation und Entnahme von Knorpelgewebe aus. Autologe mesenchymale Stammzellen sind einfach mittels Beckenkammpunktion zu gewinnen und stellen aufgrund ihres Proliferations- und chondrogenen Differenzierungsverm{\"o}gens eine vielversprechende Alternative dar. Die Tissue Engineering Division des orthop{\"a}dischen K{\"o}nig-Ludwig-Hauses in W{\"u}rzburg befasst sich nun seit mehreren Jahren in verschiedenen Versuchsreihen unter anderem mit dieser Alternative der Knorpelrekonstruktion. Vor allem die Optimierung der Nutzung von Stammzellen, die Vordifferenzierungsm{\"o}glichkeiten in vitro und das Verhalten in verschiedenen Tr{\"a}germatrizes wird erforscht. Die vorliegende Arbeit stellt eine Pilotstudie zur Anwendung von Stammzellen analog zu der in klinischer Anwendung befindlichen MACT in vivo in G{\"o}ttinger Minipigs vor. Wir haben zeigen k{\"o}nnen, wenn auch nur mit einer geringen Fallzahl und fehlenden signifikanten Aussagen, dass Stammzellen eine vielversprechende Alternative zu Chondrozyten in der Versorgung von Gelenkknorpeldefekten darstellen. Eine Verarbeitung in Kollagen I Hydrogelen ist in gleicher Weise wie mit den Chondrozyten m{\"o}glich und auch die mechanische Stabilit{\"a}t differiert nicht. Die histologischen und immunhistochemischen Auswertungen haben in den Stammzelltransplantaten gleich gute, in einigen Aspekten sogar gering bessere Ergebnisse erzielt als die bew{\"a}hrten Chondrozytentransplantate. In der Nachbehandlung schien die sofortige volle Belastung der frisch operierten Kniegelenke bei den Minipigs m{\"o}glicherweise problematisch in Bezug auf die Fixierung und den Verbleib der Gel-Transplantate im Defekt. In der Klinik ist eine zeitweise Teilbelastung und anfangs lediglich passive Bewegung des Gelenks nat{\"u}rlich problemlos m{\"o}glich. In der Zukunft werden durch Vordifferenzierung und Markierung der Stammzellen sowie durch Vorauswahl von Zellen mit einem hohen chondrogenen Differenzierungspotential die Ergebnisse von {\"a}hnlichen Versuchsreihen sicher noch optimiert werden k{\"o}nnen.},
  subject      = {Mesenchymale Stammzelle},
  language  = {de}
}
@article{DotterweichTowerBrandletal.2016,
  author    = {Dotterweich, Julia and Tower, Robert J. and Brandl, Andreas and M{\"u}ller, Marc and Hofbauer, Lorenz C. and Beilhack, Andreas and Ebert, Regina and Gl{\"u}er, Claus C. and Tiwari, Sanjay and Sch{\"u}tze, Norbert and Jakob, Franz},
  title     = {The KISS1 Receptor as an In Vivo Microenvironment Imaging Biomarker of Multiple Myeloma Bone Disease},
  series = {PLoS One},
  volume    = {11},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0155087},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146960},
  pages     = {e0155087},
  year      = {2016},
  abstract  = {Multiple myeloma is one of the most common hematological diseases and is characterized by an aberrant proliferation of plasma cells within the bone marrow. As a result of crosstalk between cancer cells and the bone microenvironment, bone homeostasis is disrupted leading to osteolytic lesions and poor prognosis. Current diagnostic strategies for myeloma typically rely on detection of excess monoclonal immunoglobulins or light chains in the urine or serum. However, these strategies fail to localize the sites of malignancies. In this study we sought to identify novel biomarkers of myeloma bone disease which could target the malignant cells and/or the surrounding cells of the tumor microenvironment. From these studies, the KISS1 receptor (KISS1R), a G-protein-coupled receptor known to play a role in the regulation of endocrine functions, was identified as a target gene that was upregulated on mesenchymal stem cells (MSCs) and osteoprogenitor cells (OPCs) when co-cultured with myeloma cells. To determine the potential of this receptor as a biomarker, in vitro and in vivo studies were performed with the KISS1R ligand, kisspeptin, conjugated with a fluorescent dye. In vitro microscopy showed binding of fluorescently-labeled kisspeptin to both myeloma cells as well as MSCs under direct co-culture conditions. Next, conjugated kisspeptin was injected into immune-competent mice containing myeloma bone lesions. Tumor-burdened limbs showed increased peak fluorescence compared to contralateral controls. These data suggest the utility of the KISS1R as a novel biomarker for multiple myeloma, capable of targeting both tumor cells and host cells of the tumor microenvironment.},
  language  = {en}
}
@article{RudertHorasHobergetal.2016,
  author    = {Rudert, Maximilian and Horas, Konstantin and Hoberg, Maik and Steinert, Andre and Holzapfel, Dominik Emanuel and H{\"u}bner, Stefan and Holzapfel, Boris Michael},
  title     = {The Wuerzburg procedure: the tensor fasciae latae perforator is a reliable anatomical landmark to clearly identify the Hueter interval when using the minimally-invasive direct anterior approach to the hip joint},
  series = {BMC Musculoskeletal Disorders},
  volume    = {17},
  journal   = {BMC Musculoskeletal Disorders},
  number    = {57},
  doi       = {10.1186/s12891-016-0908-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146031},
  year      = {2016},
  abstract  = {Background The key for successful delivery in minimally-invasive hip replacement lies in the exact knowledge about the surgical anatomy. The minimally-invasive direct anterior approach to the hip joint makes it necessary to clearly identify the tensor fasciae latae muscle in order to enter the Hueter interval without damaging the lateral femoral cutaneous nerve. However, due to the inherently restricted overview in minimally-invasive surgery, this can be difficult even for experienced surgeons. Methods and Surgical Technique In this technical note, we demonstrate for the first time how to use the tensor fasciae latae perforator as anatomical landmark to reliably identify the tensor fasciae latae muscle in orthopaedic surgery. Such perforators are used for flaps in plastic surgery as they are constant and can be found at the lateral third of the tensor fasciae latae muscle in a direct line from the anterior superior iliac spine. Conclusion As demonstrated in this article, a simple knowledge transfer between surgical disciplines can minimize the complication rate associated with minimally-invasive hip replacement.},
  language  = {en}
}