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Circular RNA circStag1 promotes bone regeneration by interacting with HuR

Bone Research 2022年第3期10卷 565-577页

作者： Gaoyang Chen Canling Long Shang Wang Zhenmin Wang Xin Chen Wanze Tang Xiaoqin He Zhiteng Bao Baoyu Tan Jin Zhao Yongheng Xie Zhizhong Li Dazhi Yang Guozhi Xiao Songlin Peng Department of spine Surgery and institute for Orthopaedic Research the Second Clinical Medical College of Jinan University(Shenzhen People’s Hospital)Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function RestorationShenzhen 518020China The First Affiliated Hospital Southern University of Science and TechnologyShenzhen 518055China The First Affiliated Hospital Jinan UniversityGuangzhou 510630China School of Medicine Southern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentShenzhen 518055China

Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of ***,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone ***,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain ***,we report that circ Stag1 is a critical osteoporosis-related circ RNA that shows significantly downregulated expression in osteoporotic bone marrow mesenchymal stem cells(BMSCs)and clinical bone tissue samples from patients with *** of circ Stag1 significantly promoted the osteogenic capability of ***,we found that circ Stag1 interacts with human antigen R(Hu R),an RNA-binding protein,and promotes the translocation of Hu R into the cytoplasm.A high cytoplasmic level of Hu R led to the activation of the Wnt signaling pathway by stabilizing and enhancing low-density lipoprotein receptor-related protein 5/6(Lrp5/6)andβ-catenin expression,thereby stimulating the osteogenic differentiation of ***,overexpression of circ Stag1 in vivo by circ Stag1-loaded adeno-associated virus(circ Stag1-AAV)promoted new bone formation,thereby preventing bone loss in ovariectomized ***,we show that circ Stag1 plays a pivotal role in promoting the regeneration of bone tissue via Hu R/Wnt signaling,which may provide new strategies to prevent bone metabolic disorders such as postmenopausal osteoporosis.

关键词： metabolism thereby promoted

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Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17^(+) γδ T cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第4期24卷 312-325页

作者： Pan LIU Mingfu LIU Deshuang XI Yiguang BAI Ruixin MA Yaomin MO Gaofeng ZENG Shaohui ZONG Department of spine Osteopathic the First Affiliated Hospital of Guangxi Medical UniversityNanning 530021China Department of Orthopaedics the Third Affiliated Hospital of Xinxiang Medical UniversityXinxiang 453000China Department of Orthopaedics Nanchong Central Hosipitalthe Second Clinical Institute of North Sichuan Medical CollegeNanchong 637000China Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry Guangxi Medical UniversityNanning 530021China College of Public Hygiene of Guangxi Medical University Nanning 530021China

Spinal cord injury(SCI)causes motor,sensory,and autonomic *** gut microbiome has an important role in SCI,while short-chain fatty acids(SCFAs)are one of the main bioactive mediators of *** the present study,we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in ***’s method was utilized to establish an SCI model in Sprague-Dawley(SD)*** animals received water containing a mixture of 150 mmol/L SCFAs after *** 21 d of treatment,the Basso,Beattie,and Bresnahan(BBB)score increased,the regularity index improved,and the base of support(BOS)value *** cord tissue inflammatory infiltration was alleviated,the spinal cord necrosis cavity was reduced,and the numbers of motor neurons and Nissl bodies were ***-linked immunosorbent assay(ELISA),real-time quantitative polymerase chain reaction(qPCR),and immunohistochemistry assay revealed that the expression of interleukin(IL)-10 increased and that of IL-17 decreased in the spinal *** promoted gut homeostasis,induced intestinal T cells to shift toward an anti-inflammatory phenotype,and promoted regulatory T(Treg)cells to secrete IL-10,affecting Treg cells and IL-17^(+)γδT cells in the spinal ***,we observed that Treg cells migrated from the gut to the spinal cord region after *** above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17^(+)γδT cells in the spinal cord,which inhibits the inflammatory response and promotes the motor function in SCI *** findings suggest that there is a relationship among gut,spinal cord,and immune cells,and the“gut-spinal cord-immune”axis may be one of the mechanisms regulating neural repair after SCI.

关键词： Short-chain fatty acids(SCFAs) Spinal cord injury(SCI) Regulatory T cells IL-17^(+)γδT cells Neuroprotection Inflammation Motor function recovery

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Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway

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Bioactive Materials 2023年第2期20卷 598-609页

作者： Ling Yu Tian Gao Wei Li Jian Yang Yinchu Liu Yanan Zhao Ping He Xuefeng Li Weichun Guo Zhengfu Fan Honglian Dai Department of Orthopedic Surgery I(spine Surgery) Renmin Hospital of Wuhan UniversityWuhan430060China Department of Bone and Soft Tissue Tumor Key Laboratory of Carcinogenesis and Translational ResearchMinistry of EducationPeking University Cancer Hospital&InstituteBeijing100000China State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Biomedical Materials and Engineering Research Center of Hubei ProvinceWuhan University of TechnologyWuhan430070China Department of Orthopedic Surgery Renmin Hospital of ShayangJingmen448200China

There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising ***,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone *** functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel *** had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone *** new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat ***,the composite promoted the attachment and proliferation of osteoblast *** was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic *** terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion *** micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect ***,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.

关键词： Critical bone defect Magnesium phosphate cement Carboxymethyl chitosan Sodium alginate Osteogenic differentiation

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Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells

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World Journal of Stem Cells 2021年第1期13卷 128-138页

作者： Yu-Hao Cheng Shu-Fen Liu Jing-Cheng Dong Qin Bian institute for Cell Engineering Johns Hopkins University School of MedicineBaltimoreMD 21205United States institute of spine Shanghai University of Traditional Chinese MedicineShanghai 200030China Department of Integrative Medicine Huashan HospitalFudan UniversityShanghai 200040China

BACKGROUND Multipotent bone marrow stromal cells(BMSCs)are adult stem cells that form functional osteoblasts and play a critical role in bone *** aging,an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of *** examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 *** To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone *** We collected BMSCs from mice at early to middle ages and compared their selfrenewal and differentiation ***,we obtained the transcriptomic profiles of BMSCs at 1 mo,3 mo,and 7 *** The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 *** transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 *** BMSCs at 7 mo showed enrichment of adipogenic and DNA repair ***,we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo,followed by increased pro-inflammatory and apoptotic *** Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

关键词： Bone marrow stromal cell Mesenchymal stem cell Mesenchymal stromal cell Aging Bone modeling and remodeling Transcriptome

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Privacy-preserving integration of multiple institutional data for single-cell type identification with scPrivacy

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Science China(Life Sciences) 2023年第5期66卷 1183-1195页

作者： Shaoqi Chen Bin Duan Chenyu Zhu Chen Tang Shuguang Wang Yicheng Gao Shaliu Fu Lixin Fan Qiang Yang Qi Liu Key Laboratory of spine and Spinal Cord Injury Repair and Regeneration(Tongji University) Ministry of EducationOrthopaedic Department of Tongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Department of AI WeBankShenzhen 518055China Translational Medical Center for Stem Cell Therapy and Institution for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Shanghai Research institute for Intelligent Autonomous Systems Shanghai 201210China

The rapid accumulation of large-scale single-cell RNA-seq datasets from multiple institutions presents remarkable opportunities for automatically cell annotations through integrative ***,the privacy issue has existed but being ignored,since we are limited to access and utilize all the reference datasets distributed in different institutions globally due to the prohibited data transmission across institutions by data regulation *** this end,we present scPrivacy,which is the first and generalized automatically single-cell type identification prototype to facilitate single cell annotations in a data privacy-preserving collaboration *** evaluated scPrivacy on a comprehensive set of publicly available benchmark datasets for single-cell type identification to stimulate the scenario that the reference datasets are rapidly generated and distributed in multiple institutions,while they are prohibited to be integrated directly or exposed to each other due to the data privacy regulations,demonstrating its effectiveness,time efficiency and robustness for privacy-preserving integration of multiple institutional datasets in single cell annotations.

关键词： preserving integration utilize

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Porous polyetheretherketone microcarriers fabricated via hydroxylation together with cellderived mineralized extracellular matrix coatings promote cell expansion and bone regeneration

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Regenerative Biomaterials 2021年第2期8卷 149-162页

作者： Shuo Sun Zixue Jiao Yu Wang Zhenxu Wu Haowei Wang Qingming Ji Yi Liu Zongliang Wang Peibiao Zhang Department of spine Surgery The First Hospital of Jilin University1 Xinmin StreetChangchun 130021China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of Sciences5625 Renmin StreetChangchun 130022China

Porous microcarriers have aroused increasing attention recently by facilitating oxygen and nutrient transfer,supporting cell attachment and growth with sufficient cell seeding *** this study,porous polyetheretherketone(PEEK)microcarriers coated with mineralized extracellular matrix(mECM),known for their chemical,mechanical and biological superiority,were developed for orthopedic *** PEEK microcarriers were derived from smooth microcarriers using a simple wet-chemistry strategy involving the reduction of carbonyl *** treatment simultaneously modified surface topology and chemical ***,the microstructure,protein absorption,cytotoxicity and bioactivity of the obtained porous microcarriers were *** deposition of mECM through repeated recellularization and decellularization on the surface of porous MCs further promoted cell proliferation and osteogenic ***,the mECM coated porous microcarriers exhibited excellent bone regeneration in a rat calvarial defect repair model in vivo,suggesting huge potential applications in bone tissue engineering.

关键词： polyetheretherketone porous microcarriers mineralized extracellular matrix cell expansion bone regeneration

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Emerging targets for glioblastoma stem cell therapy

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The Journal of Biomedical Research 2016年第1期30卷 19-31页

作者： Ahmad R.Safa Mohammad Reza Saadatzadeh Aaron A.Cohen-Gadol Karen E.Pollok Khadijeh Bijangi-Vishehsaraei Indiana University Simon Cancer Center IU School of Medicine and Goodman Campbell Brain and Spine Department of Pharmacology and Toxicology IU School of Medicine and Goodman Campbell Brain and Spine Department of Neurosurgery IU School of Medicine and Goodman Campbell Brain and Spine Herman B.Wells Center for Pediatric Research Indiana University School of MedicineIndianapolisIN 46202USA.

Glioblastoma multiforme（GBM）,designated as World Health Organization（WHO）grade IV astrocytoma,is a lethal and therapy-resistant brain cancer comprised of several tumor cell subpopulations,including GBM stem cells（GSCs）which are believed to contribute to tumor recurrence following initial response to *** evidence demonstrates that GBM tumors are initiated from *** development and use of novel therapies including small molecule inhibitors of specific proteins in signaling pathways that regulate sternness,proliferation and migration of GSCs,immunotherapy,and non-coding microRNAs may provide better means of treating *** and characterization of GSC-specific signaling pathways would be necessary to identify specific therapeutic targets which may lead to the development of more efficient therapies selectively targeting *** signaling pathways including mTOR,AKT,maternal embryonic leucine zipper kinase（MELK）,NOTCH1 and Wnt/β-catenin as well as expression of cancer stem cell markers CD133,CD44,Oct4,Sox2,Nanog,and ALDHlA1 maintain GSC ***,the data published in the Cancer Genome Atlas（TCGA）specifically demonstrated the activated PI3K/AKT/mTOR pathway in GBM *** such pathways may help to understand GSC biology and lead to the development of potential therapeutic interventions to render them more sensitive to chemotherapy and radiation ***,recent demonstration of dedifferentiation of GBM cell lines into CSC-like cells prove that any successful therapeutic agent or combination of drugs for GBM therapy must eliminate not only GSCs,but the differentiated GBM cells and the entire bulk of tumor cells.

关键词： glioblastoma multiforme stem cells dedifferentiation CD133 CD44 ALDHlAl SOX2

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Nanoengineered hydrogels as 3D biomimetic extracellular matrix with injectable and sustained delivery capability for cartilage regeneration

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Bioactive Materials 2023年第1期19卷 487-498页

作者： Penglei Cui Panpan Pan Ling Qin Xinluan Wang Xiaodong Chen Yonghui Deng Xiaoling Zhang Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200092People’s Republic of China Department of Chemistry Fudan UniversityShanghai200433People’s Republic of China Translational Medicine R&D Center Institute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518057People’s Republic of China Department of spine Surgery Beijing Jishuitan HospitalPeking University Fourth School of Clinical MedicineBeijing100035People’s Republic of China

The regeneration of articular cartilage remains a great challenge due to the difficulty in effectively enhancing spontaneous ***,the combination of implanted stem cells,suitable biomaterials and bioactive molecules has attracted attention for tissue *** this study,a novel injectable nanocomposite was rationally designed as a sustained release platform for enhanced cartilage regeneration through integration of a chitosan-based hydrogel,articular cartilage stem cells(ACSCs)and mesoporous SiO_(2)nanoparticles loaded with anhydroicaritin(AHI).The biocompatible engineered nanocomposite acting as a novel 3D biomimetic extracellular matrix exhibited a remarkable sustained release effect due to the synergistic regulation of the organic hydrogel framework and mesopore channels of inorganic mSiO_(2)nanoparticles(mSiO_(2)NPs).Histological assessment and biomechanical tests showed that the nanocomposites exhibited superior performance in inducing ACSCs proliferation and differentiation in vitro and promoting extracellular matrix(ECM)production and cartilage regeneration in *** a novel multifunctional biocompatible platform was demonstrated to significantly enhance cartilage regeneration based on the sustained release of AHI,an efficient bioactive natural small molecule for ACSCs chondrogenesis,within the hybrid matrix of hydrogel and mSiO_(2)***,the injectable nanocomposite holds great promise for use as a 3D biomimetic extracellular matrix for tissue regeneration in clinical diagnostics.

关键词： Injectable nanocomposite Mesoporous silica 3D biomimetic extracellular matrix Sustained release of anhydroicaritin Cartilage regeneration

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Identification of injury type using somatosensory and motor evoked potentials in a rat spinal cord injury model

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Neural Regeneration Research 2023年第2期18卷 422-427页

作者： Rong Li Han-Lei Li Hong-Yan Cui Yong-Can Huang Yong Hu Department of Orthopedics and Traumatology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinveChina Department of Neurosurgery Neuroscience CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouGuangdong ProvinveChina institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjinChina Shenzhen Engineering Laboratory of Orthopedic Regenerative Technologies Department of Spine SurgeryPeking University Shenzhen HospitalShenzhenGuangdong ProvinveChina Department of Orthopedics and Traumatology The University of Hong KongPokfulamHong Kong Special Administrative RegionChina

The spinal cord is at risk of injury during spinal *** intraoperative spinal co rd injury is identified early,irreve rsible impairment or loss of neurological function can be *** types of spinal cord injury result in damage to diffe rent spinal cord regions,which may cause diffe rent somatosensory and motor evoked potential signal res *** this study,we examined electrophysiological and histopathological changes between contusion,distra ction,and dislocation spinal cord injuries in a rat *** found that contusion led to the most severe dorsal white matter injury and caused considerable attenuation of both somatosensory and motor evoked *** resulted in loss of myelinated axons in the lateral region of the injured spinal cord along the rostrocaudal *** amplitude of attenuation in motor evoked potential responses caused by dislocation was greater than that caused by *** distraction injury,extracellular spaces were slightly but not significantly enlarged;somatosensory evoked potential res ponses slightly decreased and motor evoked potential responses were *** analysis showed that histological and electrophysiological findings we re significantly correlated and related to injury *** rative monitoring of both somatosensory and motor evoked potentials has the potential to identify iatrogenic spinal cord injury type during surgery.

关键词： contusion injury dislocation injury distraction injury electropnysiology heterogeneity histopathology injury mechanism motor evoked potential somatosensory evoked potential spinal cord injury

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Spinal alignment evolution with age:A prospective gait analysis study

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World Journal of Orthopedics 2017年第3期8卷 256-263页

作者： Sébastien Pesenti Benjamin Blondel Emilie Peltier Elke Viehweger Vincent Pomero Guillaume Authier Stéphane Fuentes Jean-Luc Jouve Pediatric orthopedics Timone Enfants Aix-Marseille University institute of Movement Sciences (CNRS UMR 7287) Gait Analysis Laboratory Hopital Timone Enfants Aix-Marseille University spine Unit Hopital de la Timone spine unit Timone Aix-Marseille University Neurosurgery Timone Enfants Aix-Marseille University

AIM To describe,using gait analysis,the development of spinal motion in the growing *** Thirty-six healthy children aged from 3 to 16 years old were included in this study for a gait analysis(9m-walk).Various kinematic parameters were recorded and analyzed such as thoracic angle(TA),lumbar angle(LA)and sagittal vertical axis(SVA).The kinetic parameters were the net reaction moments(N.m/kg)at the thoracolumbar and lumbosacral *** TA and LA curves were not statistically correlated to the age(respectively,P=0.32 and P=0.41).SVA increased significantly with age(Pspine biomechanics are related to the crucial role of the trunk for bipedalism acquisition,allowing stabilization despite lower limbs *** the acquisition of mature gait,the spine will mainly undergo constraints in the sagittal plane.

关键词： Sagittal balance spine biomechanics Gait analysis Thorcic kyphosis spine growth

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