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Current understanding of osteoarthritis pathogenesis and relevant new approaches

Bone Research 2022年第4期10卷 627-643页

作者： Liping Tong Huan Yu Xingyun Huang Jie Shen Guozhi Xiao Lin Chen Huaiyu Wang Lianping Xing Di Chen Research center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518005China Faculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Orthopedic surgery School of MedicineWashington University in St.LouisSt.LouisMO 63110USA School of Medicine Southern University of Science and TechnologyShenzhen 518055China Department of Wound Repair and Rehabilitation State Key Laboratory of TraumaBurns and Combined InjuryDaping HospitalArmy Medical UniversityChongqing 400042China Research center for Human Tissues and Organs Degeneration Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Pathology and Laboratory of Medicine Center for Musculoskeletal ResearchUniversity of Rochester Medical CenterRochesterNY 14642USA

Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the *** molecular mechanisms of OA are currently *** is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA *** better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA *** this review,we first focus on the epigenetic regulation of OA,with a particular focus on DNA methylation,histone modification,and microRNA regulation,followed by a summary of several key mediators in OA-associated *** then introduce several innovative techniques that have been and will continue to be used in the fields of OA and OA-associated pain,such as CRISPR,scRNA sequencing,and lineage ***,we discuss the timely updates concerning cell death regulation in OA pathology,including pyroptosis,ferroptosis,and autophagy,as well as their individual roles in OA and potential molecular targets in treating ***,our review highlights new directions on the role of the synovial lymphatic system in *** improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA.

关键词： pathogenesis swelling concerning

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Nanocomposites and bone regeneration

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Frontiers of Materials Science 2011年第4期5卷 342-357页

作者： Roshan JAMES Meng DENG Cato T. LAURENCIN Sangamesh G. KUMBAR Institute for Regenerative Engineering University of Connecticut Health Center Farmington CT 06030 USA New England musculoskeletal Institute University of Connecticut Health Center Farmington CT 06030 USA Department of Orthopaedic surgery University of Connecticut Health Center Farmington CT 06030 USA Department of Chemical Materials and Biomolecular Engineering University of Connecticut Storrs CT 06269 USA

This manuscript focuses on bone repair/regeneration using tissue engineering strategies, and highlights nanobiotechnology developments leading to novel nanocomposite systems. About 6.5 million fractures occur annually in USA, and about 550,000 of these individual cases required the application of a bone graft. Autogenous and allogenous bone have been most widely used for bone graft based therapies; however, there are significant problems such as donor shortage and risk of infection. Alternatives using synthetic and natural biomaterials have been developed, and some are commercially available for clinical applications requiring bone grafts. However, it remains a great challenge to design an ideal synthetic graft that very closely mimics the bone tissue structurally, and can modulate the desired function in osteoblast and progenitor cell populations. Nanobiomaterials, specifically nanocomposites composed of hydroxyapatite （HA） and/or collagen are extremely promising graft substitutes. The biocomposites can be fabricated to mimic the material composition of native bone tissue, and additionally, when using nano-HA （reduced grain size）, one mimics the structural arrangement of native bone. A good understanding of bone biology and structure is critical to development of bone mimicking graft substitutes. HA and collagen exhibit excellent osteoconductive properties which can further modulate the regenerative/ healing process following fracture injury. Combining with other polymeric biomaterials will reinforce the mechanical properties thus making the novel nano-HA based composites comparable to human bone. We report on recent studies using nanocomposites that have been fabricated as particles and nanofibers for regeneration of segmental bone defects. The research in nanocomposites, highlight a pivotal role in the future development of an ideal orthopaedic implant device, however further significant advancements are necessary to achieve clinical use.

关键词： bone graft substitute nanocomposite hydroxyapatite collagen nanofiber,biomimetic nanobiomaterial osteogenic segmental defect tibia defect

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A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

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Bone Research 2015年第3期3卷 164-172页

作者： Tiao Lin Wei Tong Abhishek Chandra Shao-Yun Hsu Haoruo Jia Ji Zhu Wei-Ju Tseng Michael A Levine Yejia Zhang Shi-Gui Yan X Sherry Liu Dongming Sun Wise Young Ling Qin Department of Orthopaedic surgery Perelman School of Medicine University of Pennsylvania Department of musculoskeletal Oncology The First Affiliated Hospital of Sun Yat-sen University Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology W.M.Keck center for Collaborative Neuroscience Rutgers The State University of New Jersey Department of Orthopaedic surgery School of Medicine Shihezi University Division of Endocrinology and Diabetes The Children’s Hospital of Philadelphia and Department of Pediatrics Perelman School of Medicine University of Pennsylvania Department of Physical Medicine & Rehabilitation Perelman School of Medicine University of Pennsylvania and Translational Musculoskeletal Research Center Philadelphia Veterans Affairs Medical Center Department of Orthopaedic surgery 2nd Affiliated Hospital School of Medicine Zhejiang University

Spinal cord injury（SCI）-induced bone loss represents the most severe osteoporosis with no effective *** animal studies have focused primarily on long bones at the acute stage using adolescent rodents. To mimic chronic SCI in human patients, we performed a comprehensive analysis of long-term structural and mechanical changes in axial and appendicular bones in adult rats after SCI. In this experiment, 4-month-old Fischer 344 male rats received a clinically relevant T13 contusion injury. Sixteen weeks later, sublesional femurs, tibiae,and L4 vertebrae, supralesional humeri, and blood were collected from these rats and additional non-surgery rats for micro-computed tomography（m CT）, micro-finite element, histology, and serum biochemical *** trabecular sites, extreme losses of bone structure and mechanical competence were detected in the metaphysis of sublesional long bones after SCI, while the subchondral part of the same bones showed much milder damage. Marked reductions in bone mass and strength were also observed in sublesional L4 vertebrae but not in supralesional humeri. At cortical sites, SCI induced structural and strength damage in both sub- and supralesional long bones. These changes were accompanied by diminished osteoblast number and activity and increased osteoclast number and activity. Taken together, our study revealed site-specific effects of SCI on bone and demonstrated sustained inhibition of bone formation and elevation of bone resorption at the chronic stage of SCI.

关键词： SCI bone A comprehensive study of long-term skeletal changes after spinal cord injury in adult rats

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Highly fluorescence Ta_(4)C_(3) MXene quantum dots as fluorescent nanoprobe for heavy ion detection and stress monitoring of fluorescent hydrogels

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Chinese Chemical Letters 2022年第4期33卷 1850-1854页

作者： Shouzhen Li Junfei Ma Xuelin Zhao Peide Zhu Meng Xu Yingchun Niu Dixian Luo Quan Xu State Key Laboratory of Shale Oil and Gas Enrichment Mechanisms and Effective Development National Energy Shale Oil Research and Development CenterChina University of Petroleum(Beijing)Beijing 102249China Department of musculoskeletal Tumor Senior Department of Orthopedicsthe Fourth Medical Center of PLA General HospitalBeijing 100142China Department of Laboratory Medicine Huazhong University of Science and Technology Union Shenzhen Hospital(Nanshan Hospital)Shenzhen 518000China

Compared with other transition metal Mxene derived quantum dots(MQD_(S)),Ta-based Mxene quantum dots have good functionality,but Ta-based Mxene quantum dots and their applications have not been studied so *** this paper,we report for the first time the synthesis of high fluorescence quantum yield(QY) N-doped Ta_(4)C_(3) quantum dots(N-MQDs) using Ta_(4)C_(3) quantum dots in acid reflux damaged Ta_(4)C_(3) nanosheets as precursors and ethylenediamine as nitrogen *** prepared N-MQDs have excellent blue photoluminescence(PL) properties,particle size is only 2.60 nm,QY is up to 23.4%,and good *** addition,it has been reported that N-MQDs can be used as fluorescent probe for detection of Fe;and remote force sensing analysis In liquid ion sensing,N-MQDS shows a unique selective quenching of Fe;with a detection limit as low as 2 μmol/L,and has great potential as a fast and super-sensitive fluorescent probe for the detection of heavy *** importantly,in solid mechanics sensing,the introduction of N-MQDs into self-healing hydrogels can be developed into a fluorescent hydrogel that can be used for accurate remote force measurement and applied in the field of mechanical sensing ***,Ta-based N-MQDs show excellent potential in the field of fluorescence sensing,which provides a door for multi-dimensional sensing of new materials in the future.

关键词： MXene quantum dots Fluorescent probe Fluorescent hydrogel Hydrothermal method Quantum yield

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Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors

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Bioactive Materials 2022年第1期7卷 333-340页

作者： Yang Yan Lei Zhou Zhengwang Sun Dianwen Song Yiyun Cheng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai200241China Department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai200080China Department of musculoskeletal Oncology Fudan University Shanghai Cancer CenterShanghai200032China

The treatment of malignant bone tumors by chemotherapeutics often receives poor therapeutic response due to the specific physiological bone environment,and thus calls for the development of new therapeutic ***,we reported a bone-targeted protein nanomedicine for this ***,a toxin protein,was co-assembled with a boronated polymer for intracellular protein delivery,and the formed nanoparticles were further coated with an anionic polymer poly(aspartic acid)to shield the positive charges on nanoparticles and provide the bone targeting *** prepared ternary complex nanoparticles showed high bone accumulation both in vitro and in vivo,and could reverse the surface charge property from negative to positive after locating at tumor site triggered by tumor extracellular *** boronated polymer in the de-shielded nanoparticles further promote intracellular delivery of saporin into tumor cells,exerting the anticancer activity of saporin by inactivation of *** a result,the bone-targeted and saporin-loaded nanomedicine could kill cancer cells at a low saporin dose,and efficiently prevented the progression of osteosarcoma xenograft tumors and bone metastatic breast cancer in *** study provides a facile and promising strategy to develop protein-based nanomedicines for the treatment of malignant bone tumors.

关键词： Boronated polymer Dendrimers Intracellular protein delivery Bone targeting Cancer therapy

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Utilization of longitudinal ultrasound to quantify joint soft-tissue changes in a mouse model of posttraumatic osteoarthritis

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Bone Research 2017年第3期5卷 228-234页

作者： Hao Xu Echoe M Bouta Ronald W Wood Edward M Schwarz Yongjun Wang Lianping Xing Department of Orthopaedics Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Pathology and Laboratory Medicine center for musculoskeletal Research Department of Obstetrics and Gynecology University of Rochester Medical Center

To assess the utility of longitudinal ultrasound （US） to quantify volumetric changes in joint soft tissues during the progression of posttraumatic osteoarthritis （PTOA） in mice, and validate the US results with histological findings. A longitudinal cohort of 3-month-old wild-type C57BL/6 male mice received the Hulth-Telhag surgical procedure on right knee to induce ~OA, and sham surgery on their left knee as control. US scans were performed on both knees before, 2, 4, 6, and 8 weeks post-surgery. Joint space volume and Power-Doppler （PD） volume were obtained from US images via Amira software. A paraUel cross-sectional cohort of mice was killed at each US time point, and knee joints were subjected to histological analysis to obtain synovial soft-tissue area and OARSI scores. The correlation between US joint space volume and histological synovial soft-tissue area or OARSI score was assessed via linear regression analysis. US images indicated increased joint space volume in PTOA joints over time, which was associated with synovial inflammation and cartilage damage by histology. These changes started from 2 weeks post-surgery and gradually became more severe. No change was detected in sham joints. Increased joint space volume was significantly correlated with increased synovial soft-tissue area and the OARSI score （P 〈 0.001）. PD signal was detected in the joint space of PTOA joints at 6 weeks post-surgery, which was consistent with the location of blood vessels that stained positively for CD31 and alpha-smooth muscle actin in the synovium. This study indicates that US is a cost-effective longitudinal outcome measure of volumetric and vascular changes in joint soft tissues during PTOA progression in mice, which positively correlates with synovial inflammation and cartilage damage.

关键词： OA PD USA Figure

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肌骨系统疾病临床研究方法专家共识

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中华医学杂志 2024年第23期104卷 2123-2141页

作者：中华医学会骨科学分会中国医师协会骨科医师分会国家老年疾病临床医学研究中心(湘雅医院) Department of Orthopedics Xiangya Hospital Central South University National Clinical Research Center for Geriatric Disorders Xiangya Hospital Changsha 410008 China Department of Orthopedics Third Hospital of Hebei Medical University Shijiazhuang 050051 China

肌骨系统疾病的临床研究对明确该类疾病的危险因素、规范和创新诊疗方法十分重要, 为进一步促进肌骨系统疾病临床研究规范化, 满足当前临床研究实践需要, 中华医学会骨科学分会、中国医师协会骨科医师分会及国家老年疾病临床医学研究中... 详细信息

肌骨系统疾病的临床研究对明确该类疾病的危险因素、规范和创新诊疗方法十分重要, 为进一步促进肌骨系统疾病临床研究规范化, 满足当前临床研究实践需要, 中华医学会骨科学分会、中国医师协会骨科医师分会及国家老年疾病临床医学研究中心(湘雅医院)组织专家基于国际权威肌骨系统疾病临床研究方法学标准和指南, 结合我国医疗卫生实践, 制订出符合我国国情的肌骨系统疾病临床研究方法专家共识, 旨在促进肌骨系统疾病临床研究规范化、科学化。

关键词：肌骨系统疾病临床研究专家共识

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Establishment of trauma registry at Queen Elizabeth Central Hospital(QECH), Blantyre, Malawi and mapping of high risk geographic areas for trauma

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World Journal of Emergency Medicine 2019年第1期10卷 33-41页

作者： Linda C.Chokotho Wakisa Mulwafu Mulinda Nyirenda Foster J.Mbomuwa Hemant G.Pandit Grace Le Christopher Lavy Beit Cure International Hospital Department of surgery College of Medicine University of Malawi Adult Emergency and Trauma center Queen Elizabeth Central Hospital Ministry of Health Chapel Allerton Hospital University of Leeds Nuff ield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford

BACKGROUND: Less attention is directed toward gaining a better understanding of the burden and prevention of injuries, in low and middle income countries(LMICs). We report the establishment of a trauma registry at the Adult Emergency and Trauma Centre(AETC) at Queen Elizabeth Central Hospital(QECH) in Blantyre, Malawi and identify high risk geographic areas. METHODS: We devised a paper based two-page trauma registry form. Ten data clerks and all AETC clinicians were trained to complete demographic and clinical details respectively. Descriptive data, regression and hotspot analyses were done using STATA 15 statistical package and ArcGIS(16) software ***: There were 3,747 patients from May 2013 to May 2015. The most common mechanisms of injury were assault(38.2%), and road traffi c injuries(31.6%). The majority had soft tissue injury(53.1%), while 23.8% had no diagnosis indicated. Fractures(OR 19.94 [15.34–25.93]), head injury and internal organ injury(OR 29.5 [16.29–53.4]), and use of ambulance(OR 1.57 [1.06–2.33]) were found to be predictive of increased odds of being admitted to hospital while assault(OR 0.69 [0.52–0.91]) was found to be associated with less odds of being admitted to hospital. Hot spot analysis showed that at 99% confidence interval, Ndirande, Mbayani and Limbe were the top hot spots for injury occurrence. CONCLUSION: We have described the process of establishing an integrated and potentially sustainable trauma registry. Signifi cant data were captured to provide details on the epidemiology of trauma and insight on how care could be improved at AETC and surrounding health facilities. This approach may be relevant in similar poor resource settings.

关键词： Trauma Registry Adult injuries Hot spot analysis Low and middle income countries

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Clinical outcome after surgery on schwannomas in the extremities

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World Journal of Orthopedics 2021年第10期12卷 760-767页

作者： Andreas Saine Granlund Michala Skovlund Sørensen Claus Lindkær Jensen Birthe Højlund Bech Michael Mørk Petersen musculoskeletal Tumor Section Department of Orthopedic SurgeryCopenhagen University HospitalRigshospitaletCopenhagen 2100Denmark Department of Orthopedic surgery Copenhagen University HospitalCopenhagen 2200Denmark musculoskeletal Tumor Section Department of Orthopedic SurgeryUniversity of CopenhagenCopenhagen 2100Denmark Department of Radiology RigshospitaletUniversity of CopenhagenCopenhagen 2100Denmark

BACKGROUND Schwannoma is a benign,encapsulated and slowly growing tumor originating from Schwann cells and is rarely seen in the peripheral nerve *** symptoms are soreness,radiating pain and sensory loss combined with a soft tissue *** To evaluate pre-and postoperative symptoms in patients operated for schwannomas in the extremities and investigate the rate of malignant *** In this single center retrospective study design,all patients who had surgery for a benign schwannoma in the extremities from May 1997 to January 2018 were *** location of the tumor in the extremities was divided into five groups;forearm,arm,shoulder,thigh and leg including *** locations of the tumor in the nerves were also categorized as either;proximal,distal,minor or major *** the pre-and postoperative clinical evaluation,symptoms were classified as paresthesia,local pain,radiating pain,swelling,impairment of mobility/strength and asymptomatic tumors that were found incidentally(with magnetic resonance imaging).The patients were evaluated after surgery using the following categories:Asymptomatic or symptomatic patients(radiating and/or local pain)and those with *** follow up period was from the time of surgery until last examination of the particular *** logistic regression analysis was performed to identify independent prognostic factors for postoperative significant symptoms at *** We identified 858 cases from the institutional pathology *** excluded cases with duplicate diagnoses(n=407),pathology not including schwannomas(n=157),lesions involving the torso,spine and neck(n=150)leaving 144 patients for further *** this group 99 patients underwent surgery and there were five complications recorded:2 infections(treated with antibiotics)and 3 nerve palsies(2 involving the radial nerve and one involving the median nerve)that recovered *** the end of follow-up,1.4

关键词： Schwannoma Extremities surgery Removal Symptoms Outcome

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Multi-omics characterization and therapeutic liability of ferroptosis in melanoma

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3194-3197页

作者： Yi He Yu Dong Yong Chen Guanxiong Zhang Hailun Zhang Guang Lei Yanhua Du Xiang Chen Youqiong Ye Hong Liu Department of Dermatology Hunan Key Laboratory of Skin Cancer and PsoriasisHunan Engineering Research Center of Skin Health and DiseaseXiangya Clinical Research Center for Cancer ImmunotherapyXiangya HospitalCentral South UniversityChangshaChina Shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghaiChina Department of musculoskeletal surgery Fudan University Shanghai Cancer CenterShanghaiPR China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiPR China Department of Research and Development Beijing GAP Biotechnology Co.LtdBejingChina Department of Radiation Oncology Hunan Cancer Hospital and The Affliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina

Dear Editor,Ferroptosis,an iron-dependent form of programmed cell deathdriven by excessive lipid peroxidation,1has emerged as,apromising andeffective strategy fortrigering cancer celldeath.2,3Insufficient understanding of the role of ferroptosis in melanomaprogression and the tumor microenvironment(TME)has limitedthe development of ferroptosis-targeted therapy and combina-tions with other therapeutic strategies.

关键词： therapeutic melanoma peroxidation

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