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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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3D bioprinting:current status and trends-a guide to the literature and industrial practice

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Bio-Design and manufacturing 2022年第1期5卷 14-42页

作者： Silvia Santoni Simone G.Gugliandolo mattia Sponchioni Davide moscatelli Bianca m.Colosimo Department of mechanical Engineering Politecnico di MilanoVia La Masa120156 MilanItaly Department of Chemistry Materials and Chemical Engineering“Giulio Natta”Politecnico di MilanoPiazza Leonardo da Vinci3220133 MilanItaly

The multidisciplinary research field of bioprinting combines additive manufacturing,biology and material sciences to cre-ate bioconstructs with three-dimensional architectures mimicking natural living *** high interest in the possibility of reproducing biological tissues and organs is further boosted by the ever-increasing need for personalized medicine,thus allowing bioprinting to establish itself in the field of biomedical research,and attracting extensive research efforts from companies,universities,and research institutes *** this context,this paper proposes a scientometric analysis and critical review of the current literature and the industrial landscape of bioprinting to provide a clear overview of its fast-changing and complex *** scientific literature and patenting results for 2000-2020 are reviewed and critically analyzed by retrieving 9314 scientific papers and 309 international patents in order to draw a picture of the scientific and industrial landscape in terms of top research countries,institutions,journals,authors and topics,and identifying the technology hubs *** review paper thus offers a guide to researchers interested in this field or to those who simply want to under-stand the emerging trends in additive manufacturing and 3D bioprinting.

关键词： Additive manufacturing 3D bioprinting Biofabrication Organ-on-a-chip Tissue engineering

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Serum outperforms plasma in small extracellular vesicle microRNA biomarker studies of adenocarcinoma of the esophagus

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World Journal of Gastroenterology 2020年第20期26卷 2570-2583页

作者： Karen Chiam George C mayne Tingting Wang David i Watson Tanya S irvine Tim Bright Lorelle T Smith imogen A Ball Joanne m Bowen Dorothy m Keefe Sarah K Thompson Damian J Hussey Discipline of Surgery College of Medicine and Public HealthFlinders University of South AustraliaAdelaideSA 5042Australia Flinders Health and medical Research institute Cancer Program College of Medicine and Public HealthFlinders UniversityAdelaideSA 5042Australia Discipline of Surgery The University of AdelaideAdelaideSA 5005Australia Adelaide medical School The University of AdelaideAdelaideSA 5005Australia Faculty of Health Sciences The University of AdelaideAdelaideSA 5005Australia

BACKGROUND Circulating microRNAs(miRNAs)are potential biomarkers for many ***,they can originate from non-disease specific sources,such as blood cells,and compromise the investigations for miRNA *** small extracellular vesicles(sEVs)have been suggested to provide a purer source of circulating miRNAs for biomarkers discovery,the most suitable blood sample for sEV miRNA biomarker studies has not been *** To compare the mi RNA profiles between matched serum and plasma s EV preparations to determine their suitability for biomarker *** matched serum and plasma samples were obtained from 10 healthy controls and10 patients with esophageal adenocarcinoma.s EV isolates were prepared from serum and plasma using Exo Quick Tm and quantified using Nano *** was extracted from s EV preparations with the mi RNeasy Serum/Plasma kit and profiled using the Taqman Openarray q *** overall mi RNA content and theexpression of specific mi RNAs of reported vesicular and non-vesicular origins were compared between serum and plasma s EV *** diagnostic performance of a previously identified multi-mi RNA biomarker panel for esophageal adenocarcinoma was also *** The overall mi RNA content was higher in plasma s EV preparations(480 mi RNAs)and contained 97.5%of the mi RNAs found in the serum s EV preparations(412 mi RNAs).The expression of commonly expressed mi RNAs was highly correlated(Spearman’s R=0.87,Pma and serum s EV preparations,but was consistently higher in the plasma s EV *** blood-cell mi RNAs(hsa-mi R-223-3 p,hsa-mi R-451 a,mi R-19 b-3 p,hsa-mi R-17-5 p,hsa-mi R-30 b-5 p,hsa-mi R-106 a-5 p,hsa-mi R-150-5 p and hsa-mi R-92 a-3 p)were expressed at 2.7 to 9.6 fold higher levels in the plasma s EV preparations compared to serum s EV preparations(Pin plasma s EV preparations,the percentage of protein-associated mi RNAs expressed at relatively higher levels(Ct

关键词： Biomarkers Exosomes Extracellular vesicles Circulating microRNA microRNAs Plasma Serum Blood cells Real-time polymerase chain reaction Adenocarcinoma of esophagus

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Clustering-based adaptive low-power subframe configuration with load-aware offsetting in dense heterogeneous networks

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Digital Communications and Networks 2022年第5期8卷 843-852页

作者： Dinkisa A.Bulti Jyri Hämäläinen Beneyam B.Haile Yihenew Wondie School of Electrical and Computer Engineering Addis Ababa Institute of Technology(AAiT)Ethiopia Department of Communication and Networking Aalto UniversityFinland

Heterogeneous Networks(HetNets)and cell densification represent promising solutions for the surging data traffic demand in wireless *** dense HetNets,user traffic is steered toward the Low-Power Node(LPN)when possible to enhance the user throughput and system capacity by increasing the area spectral ***,because of the transmit power differences in different tiers of HetNets and irregular service demand,a load imbalance typically exists among different serving *** offload more traffic to LPNs and coordinate the inter-Cell interference(iCi),Third-Generation Partnership Project(3GPP)has facilitated the development of the Cell Range Expansion(cre),enhanced inter-Cell interference Coordination(eiCiC)and Further enhanced iCiC(FeiCiC).in this paper,we develop a cell clustering-based load-aware offsetting and an adaptive Low-Power Subframe(LPS)*** solution allows the separation of User Association(UA)functions at the User Equipment(UE)and network server such that users can make a simple cell-selection decision similar to that in the maximum Received Signal Strength(max-RSS)based UA scheme,where the network server computes the load-aware offsetting and required LPS periods based on the load conditions of the *** proposed solution is evaluated using system-level simulations wherein the results correspond to performance changes in different service *** show that our method effectively solves the offloading and interference coordination problems in dense HetNets.

关键词： Heterogeneous networks(HetNets) 5G LTE-AUser association interference coordination Load balancing Cell range expansion Almost blank subframe Further enhanced iCiC Low-power subframe

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Enhanced CD19 activity in B cells contributes to immunodeficiency in mice deficient in the iCF syndrome gene Zbtb24

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Cellular & molecular immunology 2023年第12期20卷 1487-1498页

作者： Zhengzhou Ying Swanand Hardikar Joshua B.Plummer Tewfik Hamidi Bin Liu Yueping Chen Jianjun Shen Yunxiang mu Kevin m.mcBride Taiping Chen Department of Epigenetics and molecular Carcinogenesis The University of Texas MD Anderson Cancer CenterHoustonTX77030USA Program in Genetics and Epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical SciencesHoustonTX77030USA

immunodeficiency,centromeric instability,and facial anomalies(iCF)syndrome is a rare autosomal recessive disorder characterized by DNA hypomethylation and antibody *** is caused by mutations in DNmT3B,ZBTB24,CDCA7,or *** progress has been made in elucidating the roles of these genes in regulating DNA methylation,little is known about the pathogenesis of the life-threatening hypogammaglobulinemia ***,we show that mice deficient in Zbtb24 in the hematopoietic lineage recapitulate the major clinical features of patients with iCF ***,Vav-cre-mediated ablation of Zbtb24 does not affect lymphocyte development but results in reduced plasma cells and low levels of igm,igG1,and ***24-deficient mice are hyper and hypo-responsive to T-dependent and T-independent type 2 antigens,respectively,and marginal zone B-cell activation is ***,Zbtb24-deficient B cells show severe loss of DNA methylation in the promoter region of il5ra(interleukin-5 receptor subunit alpha),and il5ra derepression leads to elevated CD19 *** disruption of Cd19 can revert the hypogammaglobulinemia phenotype of Zbtb24-deficient *** results suggest the potential role of enhanced CD19 activity in immunodeficiency in iCF syndrome.

关键词： iCF syndrome ZBTB24 CD19 iL-5Ra hypogammaglobulinemia

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Can non-typeable Haemophilus influenzae carriage surveillance data infer antimicrobial resistance associated with otitis media?

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Pediatric investigation 2023年第1期7卷 13-22页

作者： Sophia Bowman-Derrick Tegan m.Harris Jemima Beissbarth mariana Kleinecke Katrina Lawrence Teresa m.Wozniak Amy Bleakley Angela Rumaseb michael J.Binks Robyn L.marsh Peter S.morris Amanda J.Leach Heidi Smith-Vaughan menzies School of Health Research Charles Darwin UniversityDarwinAustralia Australian e-Health Research Centre CSiRO BrisbaneAustralia Royal Darwin Hospital DarwinAustralia

importance:in remote communities of the Northern Territory,Australia,children experience high rates of otitis media(Om),commonly caused by non-typeable Haemophilus influenzae(NTHi).Few data exist on antibiotic susceptibility of NTHi from ***:To determine whether population-level nasopharyngeal NTHi antibiotic susceptibility data could inform antibiotic treatment for ***:NTHi isolates(n=92)collected from ear discharge between 2003 and 2013 were selected to time-and age-match NTHi isolates from the nasopharyngeal carriage(n=95).Antimicrobial susceptibility were *** trees and a genome-wide association study(GWAS)were performed to determine the similarity of nasopharyngeal and ear isolates at a population ***:Among 174 NTHi isolates available for antimicrobial susceptibility testing,10.3%(18/174)were resistant to ampicillin and 9.2%(16/174)were resistant to *** numbers of isolates(≤3)were resistant to tetracycline,chloramphenicol,or amoxicillin-clavulanic *** was no statistical difference in the proportion of ampicillin-resistant(P=0.11)or trimethoprim-sulfamethoxazole-resistant isolates(P=0.70)between ear discharge and nasopharynx-derived NTHi *** multi-drug resistant NTHi isolates were *** trees showed no clustering of 187 Haemophilus influenzae isolates based on anatomical niche(nasopharynx or ear discharge),and no genetic variations that distinguished NTHi derived from ear discharge and nasopharyngeal carriage were evident in the ***:in this population-level study,nasopharyngeal and ear discharge isolates did not represent distinct microbial *** results support tracking of population-level nasopharyngeal NTHi antibiotic resistance patterns to inform clinical management of Om in this population.

关键词： Haemophilus influenzae Otitis media Antimicrobial resistance

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Cathepsin D overexpression in the nervous system rescues lethality and Aβ42 accumulation of cathepsin D systemic knockout in vivo

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Acta Pharmaceutica Sinica B 2023年第10期13卷 4172-4184页

作者： Xiaosen Ouyang Willayat Y.Wani Gloria A.Benavides matthew J.Redmann Hai Vo Thomas van Groen Victor m.Darley-Usmar Jianhua Zhang Department of Pathology University of Alabama at BirminghamBirminghamAL 35294USA Department of Cell Developmental and Integrative BiologyUniversity of Alabama at BirminghamBirminghamAL 35294USA Birmingham VA medical Center University of Alabama at BirminghamBirminghamAL 35294USA

The lysosome is responsible for protein and organelle degradation and homeostasis and the cathepsins play a key role in maintaining protein quality *** D(CTSD),is one such lysosomal protease,which when deficient in humans lead to neurolipofuscinosis(NCL)and is important in removing toxic protein *** studies demonstrated that CTSD germ-line knockout-CtsdKO(CDKO)resulted in accumulation of protein aggregates,decreased proteasomal activities,and postnatal lethality on Day 26±*** of wildtype CTSD,but not cathepsin B,L or mutant CTSD,decreased a-synuclein toxicity in worms and mammalian *** this study we generated a mouse line expressing human CTSD with a floxed STOP cassette between the ubiquitous CAG promoter and the *** crossing with Nestin-cre,the STOP cassette is deleted in NESTiN+cells to allow CTSD overexpression-CTSDtg(CDtg).The CDtg mice exhibited normal behavior and similar sensitivity to subchronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(mPTP)induced *** breeding CDtg mice with CDKO mice,we found that over-expression of CTSD extended the lifespan of the CDKO mice,partially rescued proteasomal deficits and the accumulation of Aβ42 in the *** new transgenic mouse provides supports for the key role of CTSD in protecting against proteotoxicity and offers a new model to study the role of CTSD enhancement in vivo.

关键词： Cathepsin D transgenic mouse mitochondrial bioenergetics Apoptosis Cathepsin D knockout mice Dopamine Autophagy Lysosome Life expectancy Behavior

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Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis

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World Journal of Gastroenterology 2022年第10期28卷 1024-1054页

作者： Cristina m Hagen Eva Roth Theresia Reding Graf François Verrey Rolf Graf Anurag Gupta Giovanni Pellegrini Nadège Poncet Simone mafalda Rodrigues Camargo institute of Physiology University of ZurichZurich 8057ZHSwitzerland Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryZurich University HospitalZurich 8091ZHSwitzerland institute of Veterinary Pathology University of ZurichZurich 8057ZHSwitzerland

BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains ***1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer *** mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet *** To evaluate the role of LAT1 in the development of and recovery from *** AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and *** The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the ***,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout *** in females,we observed less mTOR reactivation and dysfunctional *** later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day *** contrast,pancreas morphology had returned to normal in wild-type *** LAT1 supports the regeneration of acinar cells after *** mice lacking LAT1 exh

关键词： Acute pancreatitis Amino acid transporter LAT1 metabolism Regeneration Fibrosis

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Th17 cells and their associated cytokines in liver diseases

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Cellular & molecular immunology 2010年第4期7卷 250-254页

作者： Fouad Lafdil Andrew m miller Sung Hwan Ki Bin Gao Section on Liver Biology Laboratory of Physiologic StudiesNational Institute on Alcohol Abuse and AlcoholismNational Institutes of HealthBethesdaMDUSA iNSERm U955Cre´teilFrance Faculte´de me´decine Universite´Paris 12Cre´teilFrance

T helper 17(Th17)cells are a newly identified subset of T helper cells that play important roles in host defense against extracellular bacteria as well as in the pathogenesis of autoimmune *** functions of Th17 cells are mediated via the production of several cytokines including interleukin(iL)-17 and *** studies show that the frequency of iL-171 cells is significantly elevated in a variety of chronic liver diseases including alcoholic liver disease,viral hepatitis and hepatocellular ***-17 receptor is expressed virtually on all types of liver cells,while iL-22 receptor expression is restricted to epithelial cells including hepatocytes in the ***-17 seems to play an important role in inducing liver inflammation via stimulating multiple types of liver nonparenchymal cells to produce proinflammatory cytokines and chemokines,while iL-22 appears to be an important factor in promoting hepatocyte survival and proliferation.

关键词： iL-17 iL-22 hepatitis alcoholic liver disease liver cancer

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macrophage-specific inhibition of the histone demethylase JmJD3 decreases STiNG and pathologic inflammation in diabetic wound repair

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Cellular & molecular immunology 2022年第11期19卷 1251-1262页

作者： Christopher O.Audu William J.melvin Amrita D.Joshi Sonya J.Wolf Jadie Y.moon Frank m.Davis Emily C.Barrett Kevin D.mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam C.Tsoi Sriganesh B.Sharma Tyler m.Bauer James Shadiow matthew A.Corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany Bmoore Johann EGudjonsson Andrew mSmith Katherine A.Gallagher Department of Surgery Section of Vascular SurgeryUniversity of MichiganAnn ArborMIUSA Department of microbiology and immunology University of MichiganAnn ArborMIUSA Department of medicinal Chemistry University of MichiganAnn ArborMIUSA Department of Surgery Section of General SurgeryUniversity of MichiganAnn ArborMIUSA Department of Bioengineering University of IllinoisUrbana-ChampaignChampaignILUSA Department of Dermatology University of MichiganAnn ArborMIUSA Department of Pathology University of MichiganAnn ArborMIUSA Department of Surgery University of Texas Southwestern Medical CenterDallasTXUSA

macrophage plasticity is critical for normal tissue repair following *** pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are ***,using single-cell RNA sequencing of human diabetic wounds,we identified increased JmJD3 in diabetic wound macrophages,resulting in increased inflammatory gene ***,we report that in wound healing,JmJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 ***,in the diabetic state,we found that iL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates JmJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JmJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 ***,RNA sequencing of wound macrophages isolated from mice with JmJD3-deficient myeloid cells(Jmjd3f/fLyz2cre+)identified that the STiNG gene(Tmem173)is regulated by JmJD3 in wound *** limits inflammatory cytokine production by wound macrophages during ***,in diabetic mice,its role changes to limit wound repair and enhance *** finding is important since STiNG is associated with chronic inflammation,and we found STiNG to be elevated in human and murine diabetic wound macrophages at late time ***,we demonstrate that macrophage-specific,nanoparticle inhibition of JmJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and *** together,this work highlights the central role of JmJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

关键词： wound healing epigenetics diabetes JmJD3 STiNG

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