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Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

Bone Research 2024年第1期12卷 215-226页

作者： Yuhang Liu Ruihan Hao Jia Lv Jie Yuan Xuelei Wang Churong Xu Ding Ma Zhouyi Duan Bingjun Zhang Liming Dai Yiyun Cheng Wei Lu Xiaoling Zhang department of Orthopedic surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(SJTUSM)Shanghai 200092China National Facility for Translational Medicine Shanghai 200240China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 200241China department of orthopaedic surgery The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China School of Medicine Shanghai UniversityShanghai 200444China

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat *** attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in *** this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice *** address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in ***,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived ***,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 *** knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient *** by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine ***,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

关键词： osteoarthritis metabolism inhibited

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Osteonecrosis: The perils of steroids. A review of the literature and case report

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Case Reports in Clinical Medicine 2012年第2期1卷 26-37页

作者： Ben J. Brooker Prue P. A. Keith department of orthopaedic surgery north east health wangaratta Wangaratta Australia

Non-traumatic osteonecrosis is a cause of joint pain and deformity, not uncommonly caused by corticosteroid use. Despite this, corticosteroid induced osteonecrosis is poorly represented in the literature. We performed a detailed review of corticosteroid induced osteonecrosis, including aetiology, prevention, screening, clinical presentation, investigations, staging systems and treatment. We present this in the context of a patient at our institution who developed bilateral hip, shoulder and knee osteonecrosis following high dose corticosteroid therapy for dermatomyositis.

关键词： Osteonecrosis Corticosteroids Steroids Avascular Necrosis of Bone

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Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang Institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell Research Tongji UniversityShanghai 200092China Clinical and Translation Research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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Single-cell omics:experimental workflow,data analyses and applications

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Science China Life Sciences 2024年

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biology the Institute of Biomedical Sciences and School of Life Sciences East China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary Studies Center for Quantitative Biology (CQB) Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women’s Hospital Zhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of Statistics East China Normal University Shanghai 200062 China department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of Education Orthopaedic Department Tongji Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East Hospital Bioinformatics Department School of Life Sciences and Technology Tongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public Health Shanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River Delta Zhejiang University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial scRNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

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Periprosthetic knee joint infection caused by Brucella melitensis which was first-osteoarticular brucellosis or osteoarthrosis:A case report

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World Journal of Clinical Cases 2023年第3期11卷 677-683页

作者： Thomas Stumpner Regina Kuhn Josef Hochreiter Reinhold Ortmaier department of orthopaedic surgery Ordensklinikum Linz Barmherzige SchwesternLinz 4010Austria

BACKGROUND Brucellosis is the most common zoonosis worldwide and is endemic in the Middle east,Africa,Asia,and Latin ***,it is uncommon in Central Europe,and periprosthetic infections caused by Brucella are therefore *** to the low prevalence and nonspecific clinical presentation of the disease,accurate diagnosis can be challenging;no gold standard currently exists for treating *** SUMMARY Here,we present a 68-year-old Afghan woman living in Austria with a periprosthetic knee infection caused by Brucella *** interval from total knee arthroplasty to septic loosening was five years.A profound medical history and examinations suggested that the patient had been suffering from unrecognized chronic osteoarticular brucellosis prior to total knee *** was successfully treated by two-stage revision surgery and combined antibiotic therapy over three *** Clinicians should consider brucellosis as a possible cause of chronic arthralgia and periprosthetic infection in patients originating from countries with a high brucellosis burden.

关键词： Brucellosis Arthroplasty Infection Osteoarticular Knee Case report

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Computer-assisted preoperative planning for proximal humeral fractures by minimally invasive plate osteosynthesis

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Chinese Medical Journal 2014年第18期127卷 3278-3285页

作者： Chen Yanxi Zhang Kun Qiang Minfei Li Haobo Dai Hao department of orthopaedic Trauma East Hospital Tongji UniversitySchool of Medicine Shanghai 200120 China

Background Accurate and precise preoperative planning can provide information instrumental for performing less invasive articular fracture surgery. The purpose of this study was to determine that computer-assisted preoperative planning （CAPP） has the potential to improve efficiency and time in the operating room. Methods Sixty-four patients with proximal humeral fractures were treated using locking plates by minimally invasive plate osteosynthesis （MIPO） with CAPP. The time needed for virtual segmentation, reduction, and fixation of the fracture fragments were recorded. Intra and interobserver reliabilities were analyzed using the intraclass correlation coefficient. The clinical function was analyzed using Constant Score and radiology. Results The mean total time required for CAPP of two-part, three-part, and four-part proximal humeral fractures were （13.63±1.38） minutes, （23.14±2.18） minutes, and （39.61±3.01） minutes, respectively. The intra and interobserver reliabilities for all variables were high, ranging from 0.785 to 0.992. The mean operation time was （50.1±6.7） minutes. Fifty- two patients were followed up with an average time of 34.2 months. The mean Constant Score of the injury side was （82.5 ± 9.9）. Three of the fifty-two patients had four complications. Conclusion The application of CAPP was efficient and reliable, and provided excellent clinical and radiographic outcomes for the treatment of proximal humerus fractures by MIPO.

关键词： proximal humerus fractures computer-aided design preoperative planning minimally invasive plate osteosynthesis imaging, three-dimensional

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Piezoresistive MXene/Silk fibroin nanocomposite hydrogel for accelerating bone regeneration by Re-establishing electrical microenvironment

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Bioactive Materials 2023年第4期22卷 1-17页

作者： Zhi-Chao Hu Jia-Qi Lu Tai-Wei Zhang Hai-Feng Liang Hao Yuan Di-Han Su Wang Ding Rui-Xian Lian Yu-Xiang Ge Bing Liang Jian Dong Xiao-Gang Zhou Li-Bo Jiang department of orthopaedic surgery Zhongshan HospitalFudan UniversityShanghai200032China Key Laboratory of Advanced Display and System Applications of Ministry of Education Shanghai UniversityShanghai200072China department of Orthopedics surgery Minhang HospitalFudan UniversityShanghai201100China Key Laboratory for Ultrafine Materials of Ministry of Education Frontiers Science Center for Materiobiology and Dynamic ChemistryResearch Center for Biomedical Materials of Ministry of EducationSchool of Materials Science and EngineeringEast China University of Science and TechnologyShanghai200237China department of Orthopedic surgery Zhongshan Hospital(Xiamen)Fudan UniversityXiamen361015China

The electrical microenvironment plays an important role in bone ***,the underlying mechanism by which electrical stimulation(ES)promotes bone regeneration remains unclear,limiting the design of bone microenvironment-specific electroactive ***,by simple co-incubation in aqueous suspensions at physiological temperatures,biocompatible regenerated silk fibroin(RSF)is found to assemble into nanofibrils with aβ-sheet structure on MXene nanosheets,which has been reported to inhibit the restacking and oxidation of *** electroactive hydrogel based on RSF and bioencapsulated MXene is thus prepared to promote efficient bone *** MXene/RSF hydrogel also acts as a piezoresistive pressure transducer,which can potentially be utilized to monitor the electrophysiological *** sequencing is performed to explore the underlying mechanisms,which can activate Ca^(2+)/CALM signaling in favor of the direct osteogenesis *** is found to facilitate indirect osteogenesis by promoting the polarization of M2 macrophages,as well as stimulating the neogenesis and migration of *** improvements in bone regeneration and angiogenesis are observed with MXene/RSF hydrogels under ES in ***,the MXene/RSF hydrogel provides a distinctive and promising strategy for promoting direct osteogenesis,regulating immune microenvironment and neovascularization under ES,leading to re-establish electrical microenvironment for bone regeneration.

关键词： Bone regeneration Electrical microenvironment Regenerated silk fibroin MXene Electrical stimulation

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Highly interconnected macroporous MBG/PLGA scaffolds with enhanced mechanical and biological properties via green foaming strategy

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Chinese Journal of Chemical Engineering 2021年第1期34卷 426-436页

作者： Chaobo Song Jiapeng Zhang Shuang Li Shengbin Yang Eryi Lu Zhenhao Xi Lian Cen Ling Zhao Weikang Yuan State Key Laboratory of Chemical Engineering School of Chemical EngineeringEast China University of Science and TechnologyShanghai 200237China department of Stomatology of Renji Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200127China Shanghai Key Laboratory of orthopaedic Implant Department of Orthopaedics SurgeryShanghai Ninth People's HospitalShanghai Jiao Tong University School of MedicineNo.639Zhizaoju RoadShanghai 200011China

In this study,mesoporous bioactive glass particles(MBGs) are incorporated into poly(lactic-co-glycolic acid)(PLGA) to fabricate highly interconnected macroporous composite scaffolds with enhanced mechanical and biological properties via a developed supercritical carbon dioxide(scCO_(2)) foaming method Scaffolds show favorable highly interconnected and macroporous structure through a high foaming pressure and long venting time foaming ***,scaffolds with porosity from 73% to 85%,pore size from 120 μm to 320 μm and interconnectivity of over 95% are controllably fabricated at MBG content from 0 wt% to 20 wt%.In comparison with neat PLGA scaffolds,composite scaffolds perform improved strength(up to 1.5 folds) and Young's modulus(up to 3 folds).The interconnected macroporous structure is beneficial to the ingrowth of *** importantly,composite scaffolds also provide a more promising microenvironment for cellular proliferation and adhesion with the release of bioactive ***,MBG/PLGA scaffolds developed by the green foaming strategy in this work show promising morphological,mechanical and biological features for tissue regeneration.

关键词： Scaffold Mesoporous bioactive glass Supercritical carbon dioxide Foaming Poly(lactic-co-glycolic acid)

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Distal tibial fracture： An ideal indication for external fixation using locking plate

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Chinese Journal of Traumatology 2016年第2期19卷 104-108页

作者： Jing-wei Zhang Nabil A. Ebraheim Ming Li Xian-Feng He Joshua Schwind Li-Mei Zhu Yi-Hui Yu orthopaedic surgery Ningbo 6th Hospital 1059 East Zhongshan Road Ningbo 315040 Zhejiang Province China department of orthopaedic surgery University of Toledo Toledo OH 42614 USA

Objective： To evaluate the feasibility and efficiency of one-stage external fixation by using locking plate in distal tibial fractures. Methods： In this non-control prospective study, 28 patients with distal tibial fractures were included and underwent one-stage external fixation by using locking plate. There were 21 males and 7 females, with a mean age of 43 years （19-63）. According to AO/OTA fracture classification, there were 9 cases of Type A1, 9 of Type A2, 10 of Type A3 fractures. There were 21 close and 7 open fractures. The locking plate was placed on the anteromedial aspect of the tibia with 4-5 bicortical screws inserted in both distal metaphysis and diaphysis. The radiographic and clinic results were evaluated. Results： All patients were followed up for the average of 16 months （ranging from 12 to 21 months）. The average surgery duration was 38 （25-60） minutes. The mean time to fracture healing were 14.6 ± 2.67, 17.5 ± 3.66, and 18.4±3.37 （p 〈 0.05） weeks in type A1, A2, and A3 fractures respectively. By the end of the follow-ups, the mean AOFAS score were 96.11 ± 2.32, 92.67 ± 1.80 and 92.00± 2.06 （p 〉 0.05） in type A1, A2, and A3 fractures respectively. None of nonunion, deep infection, or breakage of screw or plate were observed. Conclusions： Distal tibial fracture was the ideal indication for external fixation using locking plate. The external plating is characterized by ease of performance, less invasive, fewer soft tissue impingement, improved cosmesis, and convenient for removal.

关键词： Tibia fracturesurgeryExternal fixationLocking plate

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Deformation and stress distribution of the human foot after plantar ligaments release:A cadaveric study and finite element analysis

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Science China(Life Sciences) 2011年第3期54卷 267-271页

作者： LIANG Jun YANG YunFeng YU GuangRong NIU WenXin WANG YuBin Sports Medicine department of Shanghai east Hospital Tongji University Shanghai 200120 China orthopaedic department of Tongji Hospital Tongji University Shanghai 200065 China School of Biological Science and Medical Engineering Beihang University Beijing 100191 China

The majority of foot deformities are related to arch collapse or instability,especially the longitudinal *** the relationship between the plantar fascia and arch height has been previously investigated,the stress distribution remains *** aim of this study was to explore the role of the plantar ligaments in foot arch *** constructed a geometrical detailed three-dimensional (3-D) finite element (FE) model of the human foot and ankle from computer tomography *** model comprised the majority of joints in the foot as well as bone segments,major ligaments,and plantar soft *** of the plantar fascia and other ligaments was simulated to evaluate the corresponding biomechanical effects on load distribution of the bony and ligamentous *** intrinsic ligaments of the foot arch were sectioned to simulate different pathologic situations of injury to the plantar ligaments,and to explore bone segment displacement and stress *** validity of the 3-D FE model was verified by comparing results with experimentally measured data via the displacement and von Mise stress of each bone *** fascia release decreased arch height,but did not cause total collapse of the foot *** longitudinal foot arch was lost when all the four major plantar ligaments were sectioned *** fascia release was compromised by increased strain applied to the plantar ligaments and intensified stress in the midfoot and metatarsal *** redistribution among the centralized metatarsal bones and focal stress relief at the calcaneal insertion were *** 3-D FE model indicated that plantar fascia release may provide relief of focal stress and associated heel ***,these operative procedures may pose a risk to arch stability and clinically may produce dorsolateral midfoot *** initial strategy for treating plantar fasciitis should be non-operative.

关键词： biomechanics finite element analysis foot arch ligament stress

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