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Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky simon von kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

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Accelerated tooth movement in Rsk2-deficient mice with impaired cementum formation

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International Journal of Oral Science 2020年第4期12卷 338-345页

作者： Cita Nottmeier Maximilian G.Decker Julia Luther simon von kroge Bärbel Kahl-Nieke Michael Amling Thorsten Schinke Julian Petersen Till Koehne Department of Orthodontics University Medical Center Hamburg-EppendorfHamburgGermany Institute of Osteology and Biomechanics University Medical Center Hamburg-EppendorfHamburgGermany

Coffin–Lowry–Syndrome(CLS)is a X-linked mental retardation characterized by skeletal dysplasia and premature tooth *** and others have previously demonstrated that the ribosomal S6 kinase RSK2,mutated in CLS,is essential for bone and cementum formation;however,it remains to be established whether RSK2 plays also a role in mechanically induced bone remodeling during orthodontic tooth movement(OTM).We,therefore,performed OTM in wild-type(WT)mice and Rsk2-deficient mice using Nitinol tension springs that were fixed between the upper left molars and the *** untreated contralateral molars served as internal *** 12 days of OTM,the jaws were removed and examined by micro-computed tomography(μCT),decalcified histology,and *** analysis of the untreated teeth confirmed that the periodontal phenotype of Rsk2-deficient mice is characterized by alveolar bone loss and hypoplasia of root *** of OTM usingμCT revealed that OTM was more than two-fold faster in Rsk2-deficient mice as compared to *** also observed that OTM caused alveolar bone loss and root resorptions in WT and Rsk2-deficient ***,quantification of these orthodontic side effects revealed no differences between WT and Rsk2-deficient *** together,Rsk2 loss-of-function accelerates OTM in mice without causing more side effects.

关键词： impaired deficient movement

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The WNT1^(G177C) mutation specifically affects skeletal integrity in a mouse model of osteogenesis imperfecta type XV

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Bone Research 2021年第4期9卷 593-605页

作者： Nele Vollersen Wenbo Zhao Tim Rolvien Fabiola Lange Felix Nikolai Schmidt Stephan Sonntag Doron Shmerling simon von kroge Kilian Elia Stockhausen Ahmed Sharaf Michaela Schweizer Meliha Karsak Bjorn Busse Ernesto Bockamp Oliver Semler Michael Amling Ralf Oheim Thorsten Schinke Timur Alexander Yorgan Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany PolyGene AG 8153 RumlangSwitzerland ETH Phenomics Center(EPIC) ETH Zurich8092 ZurichSwitzerland Neuronal and Cellular Signal Transduction Center for Molecular Neurobiology Hamburg(ZMNH)University Medical Center Hamburg-Eppendorf20246 HamburgGermany Center for Molecular Neurobiology Hamburg(ZMNH) University Medical CenterHamburg-Eppendorf20246 HamburgGermany Institute for Translational Immunology and Research Center for Immunotherapy University Medical CenterJohannes Gutenberg UniversityD 55131 MainzGermany Faculty of Medicine and University Hospital Cologne Department of PediatricsUniversity of Cologne50937 CologneGermany

The recent identification of homozygous WNT1 mutations in individuals with osteogenesis imperfecta type XV(OI-XV)has suggested that WNT1 is a key ligand promoting the differentiation and function of bone-forming *** such aninfluence was supported by subsequent studies,a mouse model of OI-XV remained to be ***,we introduced a previously identified disease-causing mutation(G177C)into the murine Wnt1 *** Wnt1^(G177C/G177C)mice were viable and did not display defects in brain development,but the majority of 24-week-old Wnt1^(G177C/G177C)mice had skeletal *** increased bone fragility was not fully explained by reduced bone mass but also by impaired bone matrix ***,the homozygous presence of the G177C mutation did not interfere with the osteoanabolic influence of either parathyroid hormone injection or activating mutation of LRP5,the latter mimicking the effect of sclerostin ***,transcriptomic analyses revealed that short-term administration of WNT1 to osteogenic cells induced not only the expression of canonical WNT signaling targets but also the expression of genes encoding extracellular matrix *** together,our data demonstrate that regulating bone matrix quality is a primary function of *** further suggest that individuals with WNT1 mutations should profit from existing osteoanabolic therapies.

关键词： WNT1 skeletal impaired

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Photoelectrochemical Iron-Catalyzed C(sp^(3))-H Borylation of Alkanes in a Position-Selective Manner

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CCS Chemistry 2024年第6期6卷 1430-1438页

作者： Wen Wei Bin Wang simon L.Homölle Jinbin Zhu Yanjun Li Tristan von Münchow Isaac Maksso Lutz Ackermann Institut für Organische und Biomolekulare Chemie Georg-August-Universität Göttingen37077 Göttingen

Catalytic C-H borylation is of prime topical importance,since easily available feedstock chemicals can thereby be transformed into valuable transient functional groups in the absence of directing ***,we disclose an iron-catalyzed C(sp^(3))-H borylation of simple,non-prefunctionalized alkanes,providing access to value-added products in a single step by means of *** power of merging photo-and electrochemistry was mirrored by ample scope and exceedingly mild reaction ***,an outstanding position-selectivity in favor of primary C(sp^(3))-H proved viable within the photoelectrochemical borylation through a chemo-selective anodic overoxidation *** ferro-photoelectrochemistry strategy avoids toxic precious transition metals,enabling C(sp^(3))-H borylations in a site-selective fashion.

关键词： photoelectrocatalysis C(sp^(3))-H borylation iron catalysis position-selectivity chlorine radical

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A good gut feeling on Sarm1-mediated axon degeneration

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Protein & Cell 2021年第8期12卷 596-598页

作者： Victoria E.von Saucken David J.simon Department of Biochemistry Weill Cornell Medical College Tri-Institutional MD-Ph D Program Weill Cornell Medicine Rockefeller University Memorial Sloan Kettering Cancer Center

Axons,the cable-l ike projections of neurons,experience a wide range of stressors throughout their *** result of any one of these challenges can be catastrophic,promoting degeneration of the *** degeneration is an active signaling process observed in traumatic brain injury,chemotherapy-induced peripheral neuropathies,and neurodegen erative disease (simon and Watkins,2018;Coleman and Hoeke,2020).As a result,tremendous efforts have been made to identify biological targets that can be harnessed to block axon degeneration to treat these *** promising candidate is Sarm1 (sterile alpha and TIR motif containing protein 1),a member of the Myd88 immune adaptor protein family that itself has no clear role in innate immunity.

关键词： SARM1 ACTIVATION TRIGGERS DEATH

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Longitudinal Changes in Sarcopenia Criteria in Older Men with Low Skeletal Muscle Mass Index:A 2-Year Observational Study

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Journal of Science in Sport and Exercise 2019年第1期1卷 59-68页

作者： Wolfgang Kemmler simon von Stengel Stephanie Kast Cornel Sieber Ellen Freiberger Institute of Medical Physics Friedrich-Alexander University Erlangen-NürnbergHenkestrasse 9191052 ErlangenGermany Institute of Biomedicine of Aging University of Erlangen-Nürnberg90408 NürnbergGermany

Purpose Declines in muscle mass and function are inevitable during the aging ***,what is the“normal age appropriate”decline of muscle mass and function?Further,is this decline uniform for muscle mass versus functions or between different functional abilities?Using recognized Sarcopenia criteria[*** muscle mass index(SMI)defined as appendicular skeletal muscle mass/height(kg/m^(2)),handgrip strength,gait velocity],the aim of the present project was to determine corresponding changes in community-dwelling men 70 years+with low SMI over a 2-year *** One hundred and seventy-seven(177)men within the lowest SMI quartile of a recent epidemiologic study(n=965)were included in the 2-year follow-up *** mass was determined via direct-segmental,multi-frequency Bio-Impedance-Analysis,handgrip strength was tested with a Jamar hand-dynamometer and habitual gait speed was assessed with photo sensors applying the 10 m *** SMI,handgrip strength and gait velocity all declined significantly(P<0.001;effect size,d′0.39-1.17),however,with significantly higher reductions(P<0.001)in functional compared with morphologic Sarcopenia criteria(P≤0.006).Less expected,handgrip strength featured a fourfold higher decline compared with gait velocity(−12.8±10.9%versus−3.5±9.0%).Conclusion We provided evidence for significant non-uniform changes of Sarcopenia criteria in a cohort of community dwell-ing men 70 years+with low *** doubt that this result might be a particularity of the selected cohort;however,studies with other(older)cohorts should address this issue in more *** practical relevance,our data further give implications for the prioritization of interventions that address Sarcopenia criteria in older community-dwelling men.

关键词： Sarcopenia Muscle mass Handgrip strength Gait velocity Aging Older men

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Management of occluded self-expanding biliary metal stents in malignant biliary disease

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 49-54页

作者： simon Nennstiel Isolde Tschurtschenthaler Bruno Neu Hana Algül Monther Bajbouj Roland M. Schmid Stefan von Delius Andreas Weber Klinik und Poliklinik fur Innere Medizin Ⅱ Klinikum rechts der Isar der Technischen Universitar Manchen Ismaninger Straβe 22 Munich 81675 Germany Medizinische Klinik II Krankenhaus Landshut-Achdorf Academic Teaching Hospital Technische Universitar Munchen Achdorferweg 3 Landshut 84036Germany

Background: Occlusion of self-expanding metal stents(SEMS) in malignant biliary obstruction occurs in up to 40% of patients. This study aimed to compare the different techniques to resolve stent occlusion in our collective of ***: Patients with malignant biliary obstruction and occlusion of biliary metal stent at a tertiary referral endoscopic center were retrospectively identified between April 1, 1994 and May 31, 2014. The clinical records were further analyzed regarding the characteristics of patients, malignant strictures, SEMS,management strategies, stent patency, subsequent interventions, survival time and case ***: A total of 108 patients with biliary metal stent occlusion were identified. Seventy-nine of these patients were eligible for further analysis. Favored management was plastic stent insertion in 73.4% patients. Second SEMS were inserted in 12.7% patients. Percutaneous transhepatic biliary drainage and mechanical cleansing were conducted in a minority of patients. Further analysis showed no statistically significant difference in median overall secondary stent patency(88 vs. 143 days, P = 0.069), median survival time(95 vs. 192 days, P = 0.116), median subsequent intervention rate(53.4% vs. 40.0%, P = 0.501)and median case charge(€5145 vs. €3473, P = 0.803) for the treatment with a second metal stent insertion compared to plastic stent insertion. In patients with survival time of more than three months,significantly more patients treated with plastic stents needed re-interventions than patients treated with second SEMS(93.3% vs. 57.1%, P = 0.037).Conclusions: In malignant biliary strictures, both plastic and metal stent insertions are feasible strategies for the treatment of occluded SEMS. Our data suggest that in palliative biliary stenting, patients especially those with longer expected survival might benefit from second SEMS insertion. Careful patient selection is important to ensure a proper decision for either management

关键词： Self-expanding metal stents Biliary tract neoplasms Endoscopic retrograde cholangiopancreatography Biliary tract diseases Complications

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Non-optical polyp-based resect and discard strategy:A prospective clinical study

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World Journal of Gastroenterology 2022年第19期28卷 2137-2147页

作者： Mahsa Taghiakbari Celia Hammar Mira Frenn Roupen Djinbachian Heiko Pohl Erik Deslandres simon Bouchard Mickael Bouin Daniel von Renteln Department of Gastroenterology Montreal University Hospital Research Center(CRCHUM)Montréal H2X 0A9QuebecCanada Department of Gastroenterology University of MontrealFaculty of MedicineMontreal H2X 0A9QuebceCanada Department of Internal Medicine University of Montreal Hospital Center(CHUM)Montreal H2X 0A9QuebecCanada Department of Medicine Veterans Affairs Medical CenterWhite River JunctionVT 05009United States Department of Gastroenterology Dartmouth Geisel School of Medicine and The Dartmouth InstituteHanoverNH 03755United States

BACKGROUND Post-polypectomy surveillance intervals are currently determined based on pathology *** To evaluate a polyp-based resect and discard model that assigns surveillance intervals based solely on polyp number and *** Patients undergoing elective colonoscopies at the Montreal University Medical Center were enrolled *** polyp-based strategy was used to assign the next surveillance interval using polyp size and *** intervals were also assigned using optical diagnosis for small polyps(<10 mm).The primary outcome was surveillance interval agreement between the polyp-based model,optical diagnosis,and the pathology-based reference standard using the 2020 United States Multi-Society Task Force *** outcomes included the proportion of reduction in required histopathology evaluations and proportion of immediate post-colonoscopy recommendations provided to *** Of 944 patients(mean age 62.6 years,49.3%male,933 polyps)were *** surveillance interval agreement for the polyp-based strategy was 98.0%[95%confidence interval(CI):0.97-0.99]compared with pathology-based *** diagnosis-based intervals achieved 95.8%(95%CI:0.94-0.97)agreement with *** using the polyp-based strategy and optical diagnosis,the need for pathology assessment was reduced by 87.8%and 70.6%,*** polyp-based strategy provided 93.7%of patients with immediate surveillance interval recommendations vs 76.1%for optical *** The polyp-based strategy achieved almost perfect surveillance interval agreement compared with pathology-based assignments,significantly reduced the number of required pathology evaluations,and provided most patients with immediate surveillance interval recommendations.

关键词： Colonoscopy Colorectal pathology Colorectal adenomas Endoscopy Surveillance Optical diagnosis

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A concept for multiterawatt fibre lasers based on coherent pulse stacking in passive cavities

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Light(Science & Applications) 2014年第1期3卷 62-68页

作者： Sven Breitkopf Tino Eidam Arno Klenke Lorenz von Grafenstein Henning Carstens simon Holzberger Ernst Fill Thomas Schreiber Ferenc Krausz Andreas Tunnermann Ioachim Pupeza Jens Limpert Institute of Applied Physics Abbe Center of PhotonicsFriedrich-Schiller-Universitat Jena07745 JenaGermany Helmholtz Institute Jena 07743 JenaGermany Max Planck Institute of Quantum Optics 85748 GarchingGermany Ludwig Maximilians University Munchen Department of Physics85748 GarchingGermany Fraunhofer Institute for Applied Optics and Precision Engineering 07745 JenaGermany

Since the advent of femtosecond lasers,performance improvements have constantly impacted on existing applications and enabled novel ***,one performance feature bearing the potential of a quantum leap for high-field applications is still not available:the simultaneous emission of extremely high peak and average *** applications such as laser particle acceleration require exactly this performance regime and,therefore,challenge laser technology at *** the one hand,canonical bulk systems can provide pulse peak powers in the multi-terawatt to petawatt range,while on the other hand,advanced solid-state-laser concepts such as the thin disk,slab or fibre are well known for their high efficiency and their ability to emit high average powers in the kilowatt range with excellent beam *** this contribution,a compact laser system capable of simultaneously providing high peak and average powers with high wall-plug efficiency is proposed and *** concept is based on the temporal coherent combination(pulse stacking)of a pulse train emitted from a high-repetition-rate femtosecond laser system in a passive enhancement ***,the pulse energy is increased at the cost of the repetition rate while almost preserving the average *** concept relies on a fast switching element for dumping the enhanced pulse out of the *** switch constitutes the key challenge of our *** this challenge could,for the first time,allow the highly efficient dumping of joule-class pulses at megawatt average power levels and lead to unprecedented laser parameters.

关键词： cavity dumping cavity enhancement coherent pulse addition high average power and high peak power ultrafast lasers

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Atypical hematological manifestation of celiac disease:A case report of aplastic anemia in a 2-year-old child and review of the literature

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Pediatric Investigation 2021年第2期5卷 159-162页

作者： Thea von Graffenried Mattia Rizzi Michel Russo Andreas Nydegger simon Kayemba-Kay’s Pediatric Gastroenterology Unit Department of PediatricsUniversity of LausanneCentre Hospitalier Universitaire VaudoisLausanneSwitzerland Hemato-Oncology Unit Department of PediatricsUniversity of LausanneSwitzerland Department of Pediatrics Centre Hospitalier du Valais RomandSionSwitzerland Department of Pediatrics Centre Hospitalier des Pays de MorlaixFrance

Introduction Celiac disease typically presents with symptoms of malabsorption,but extraintestinal manifestations are increasingly *** anemia as the mode of celiac disease presentation is extremely rare in *** presentation We report a 2-year-old boy who presented with loose stools,loss of appetite,and bicytopenia with severe aregenerative normocytic ***,including bone marrow aspirate and biopsy,revealed aplastic *** for malabsorption showed increased plasma concentrations of anti-transglutaminase and anti-gliadin antibodies.A duodenal biopsy confirmed the histologic features of celiac *** child received a packed red cell transfusion and was started on a gluten-free diet,with a very good prognosis and normalization of both his blood and histological *** the best of our knowledge,our report is the sixth pediatric case in the *** Screening for celiac disease should be performed in children with unexplained hematological abnormalities such as aplastic anemia with or without gastrointestinal symptoms.

关键词： Aplastic anemia Celiac disease Child Gluten-free diet

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