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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng Department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of spinal cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital Department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic research Center of Shandong university&Advanced Medical research institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived *** effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in *** results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft *** CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve ***,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

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Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China Life Sciences 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cell research Tongji University Shanghai Tenth People's Hospital School of MedicineTongji University Key Laboratory of spine and spinal cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji University Shanghai institute of Stem Cell research and Clinical Translation

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription, the epigenome and development. Nevertheless, previous studies using knockdown（KD） or knockout（KO） models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles, as well as compensatory effects among TET family members, which has made the understanding of the enzymatic role of TET not accurate enough. To solve this problem, we successfully generated mice catalytically inactive for specific Tet members(Tetm/m). We observed that, compared with the reported KO mice, mutant mice exhibited distinct developmental defects, including growth retardation, sex imbalance, infertility, and perinatal lethality. Notably, Tetm/mmouse embryonic stem cells（mESCs） were successfully established but entered an impaired developmental program, demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA methylation. Intriguingly, Tet3, traditionally considered less critical for m ESCs due to its lower expression level, had a significant impact on the global hydroxymethylation, gene expression, and differentiation potential of mESCs. Notably, there were common regulatory regions between Tet1 and Tet3 in pluripotency regulation. In summary, our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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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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Cytochrome P45026A1 Contributes to the Maintenance of Neuropathic Pain

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Neuroscience Bulletin 2024年第3期40卷 293-309页

作者： De-Li Cao Ling-Jie Ma Bao-Chun Jiang Qiang Gu Yong-Jing Gao institute of Pain Medicine and Special Environmental Medicine Co-innovation Center of NeuroregenerationNantong UniversityNantong226019China nantong university Medical School Nantong226001China Department of Pain Management The Affiliated Hospital of Nantong UniversityNantong226001China

The cytochrome P450 proteins(CYP450s)have been implicated in catalyzing numerous important biological reactions and contribute to a variety of ***26A1,a member of the CYP450 family,carries out the oxidative metabolism of retinoic acid(RA),the active metabolite of vitamin *** we report that CYP26A1 was dramatically upregulated in the spinal cord after spinal nerve ligation(SNL).CYP26A1 was mainly expressed in spinal neurons and *** analysis displayed that the content of all-trans-RA(at-RA),the substrate of CYP26A1,was reduced in the spinal cord on day 7 after *** of CYP26A1 by siRNA or inhibition of CYP26A1-mediated at-RA catabolism by talarozole relieved the SNL-induced mechanical allodynia during the maintenance phase of neuropathic *** also reduced SNL-induced glial activation and proinflammatory cytokine production but increased anti-inflammatory cytokine(IL-10)*** RA receptors RARα,RXRβ,and RXRγwere expressed in spinal neurons and glial *** promoter of Il-10 has several binding sites for RA receptors,and at-RA directly increased Il-10 mRNA expression in ***,intrathecal IL-10 attenuated SNL-induced neuropathic pain and reduced the activation of astrocytes and ***,the inhibition of CYP26A1-mediated at-RA catabolism alleviates SNL-induced neuropathic pain by promoting the expression of IL-10 and suppressing glial ***26A1 may be a potential therapeutic target for the treatment of neuropathic pain.

关键词： CYP26A1 Microglia Astrocytes ERK P38 IL-10 Neuropathic pain

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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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L-Type Calcium Channel Modulates Low-Intensity Pulsed Ultrasound-Induced Excitation in Cultured Hippocampal Neurons

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Neuroscience Bulletin 2024年第7期40卷 921-936页

作者： Wen-Yong Fan Yi-Ming Chen Yi-Fan Wang Yu-Qi Wang Jia-Qi Hu Wen-Xu Tang Yi Feng Qian Cheng Lei Xue State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghai 200433China Department of Physiology and Neurobiology School of Life SciencesFudan UniversityShanghai 200438China institute of Acoustics School of Physics Science and EngineeringTongji UniversityShanghai 200092China Key Laboratory of spine and spinal cord Injury Repair and Regeneration of Ministry of Education Tongji UniversityShanghai 200070China Center for Rehabilitation Medicine Department of Pain ManagementZhejiang Provincial People's HospitalAffliated People's HospitalHangzhou Medical CollegeHangzhou 310014China Department of Critical Care Medicine Shanghai General HospitalShanghai Jiaotong University School of MedicineShanghai 200080China Shanghai research institute for Intelligent Autonomous Systems Tongji UniversityShanghai 201210China research institute of Intelligent Complex Systems Fudan UniversityShanghai 200433China

As a noninvasive technique,ultrasound stimulation is known to modulate neuronal activity both in vitro and in *** latest explanation of this phenomenon is that the acoustic wave can activate the ion channels and further impact the electrophysiological properties of targeted ***,the underlying mechanism of low-intensity pulsed ultrasound(LIPUS)-induced neuro-modulation effects is still ***,we characterize the excitatory effects of LIPUS on spontaneous activity and the intracellular Ca^(2+)homeostasis in cultured hippocampal *** whole-cell patch clamp recording,we found that 15 min of 1-MHz LIPUS boosts the frequency of both spontaneous action potentials and spontaneous excitatory synaptic currents(sEPSCs)and also increases the amplitude of sEPSCs in hippocampal *** phenomenon lasts for>10 min after LIPUS *** with Ca^(2+)imaging,we clarified that LIPUS increases the[Ca^(2+)]cyto level by facilitating L-type Ca^(2+)channels(LTCCs).In addition,due to the[Ca^(2+)]cyto elevation by LIPUS exposure,the Ca^(2+)-dependent CaMKII-CREB pathway can be activated within 30 min to further regulate the gene transcription and protein *** work suggests that LIPUS regulates neuronal activity in a Ca^(2+)-dependent manner via *** may also explain the multi-activation effects of LIPUS beyond *** stimulation potentiates spontaneous neuronal activity by increasing Ca^(2+)influx.

关键词： Low-intensity pulsed ultrasound Neuromodulation L-type calcium channel Hippocampal neuron

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Epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China:a hospital-based retrospective study

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Neural Regeneration research 2024年第5期19卷 1126-1132页

作者： Hengxing Zhou Yongfu Lou Lingxiao Chen Yi Kang Lu Liu Zhiwei Cai David BAnderson Wei Wang Chi Zhang Jinghua Wang Guangzhi Ning Yanzheng Gao Baorong He Wenyuan Ding Yisheng Wang Wei Mei Yueming Song Yue Zhou Maosheng Xia Huan Wang Jie Zhao Guoyong Yin Tao Zhang Feng Jing Rusen Zhu Bin Meng Li Duan Zhongmin Zhang Desheng Wu Zhengdong Cai Lin Huang Zhanhai Yin Kainan Li Shibao Lu Shiqing Feng Department of Orthopedics The Second HospitalCheeloo College of MedicineShandong UniversityShandongChina Department of Orthopedics Shandong University Center for OrthopedicsQilu HospitalCheeloo College of MedicineShandong UniversityShandongChina Department of Orthopedics Tianjin Medical University General HospitalInternational Science and Technology Cooperation Base of Spinal Cord InjuryTianjin Key Laboratory of Spine and Spinal CordTianjinChina Faculty of Medicine and Health The Back Pain Research TeamSydney Musculoskeletal HealthThe Kolling InstituteUniversity of SydneySydneyNSWAustralia Department of spine Surgery Honghui HospitalXi’an Jiaotong UniversityXi’anShaanxi ProvinceChina Department of Burns and Plastic Surgery The Fourth Medical Center of Chinese PLA General HospitalBeijingChina Faculty of Medicine and Health School of Health SciencesUniversity of SydneyNSWAustralia Sydney spine institute BurwoodSydneyNSWAustralia Laboratory of Epidemiology Tianjin Neurological InstituteDepartment of NeurologyTianjin Medical University General Hospital&Tianjin Neurological InstituteKey Laboratory of Post-Neuroinjury Neuro-repair and Regeneration in Central Nervous SystemMinistry of Education and Tianjin CityTianjinChina Department of Orthopedics Henan Provincial People’s HospitalZhengzhouHenan ProvinceChina Department of spinal Surgery The Third Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Orthopedics The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina Department of spine Surgery Zhengzhou Orthopedics HospitalZhengzhouHenan ProvinceChina Department of Orthopedic Surgery and Orthopedic research institute West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Orthopedics Xinqiao HospitalArmy Medical UniversityChongqingChina Department of Orthopedics The First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Department of spinal Surgery Shengj

Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even *** has the largest population of patients with traumatic spinal cord *** studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been *** the best of our knowledge,no national-level study of treatment status and economic burden has been *** retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national *** included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of *** epidemiological and clinical features,treatment status,and total and daily costs were *** in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression *** percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent *** 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 *** total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 ho

关键词： China clinical features costs epidemiology methylprednisolone sodium succinate methylprednisolone retrospective study traumatic spinal cord injury treatment

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Role of necroptosis in spinal cord injury and its therapeutic implications

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BIOCELL 2023年第4期47卷 739-749页

作者： JIAWEI FU CHUNSHUAI WU GUANHUA XU JINLONG ZHANG YIQIU LI CHUNYAN JI ZHIMING CUI The Affiliated Hospital 2 of nantong university Nantong UniversityThe First People’s Hospital of NantongNantong226001China Key Laboratory for Restoration Mechanism and Clinical Translation of spinal cord Injury Nantong226001China research institute for spine and spinal cord disease of nantong university Nantong226001China

spinal cord injury(SCI),a complex neurological disorder,triggers a series of devastating neuropathological events such as ischemia,oxidative stress,inflammatory events,neuronal apoptosis,and motor ***,the classical necrosome,which consists of receptor-interacting protein(RIP)1,RIP3,and mixed-lineage kinase domain-like protein,is believed to control a novel type of programmed cell death called necroptosis,through tumour necrosis factor-alpha/tumour necrosis factor receptor-1 signalling or other *** studies reported that necroptosis plays an important role in neural cell damage,release of intracellular pro-inflammatory factors,lysosomal dysfunction and endoplasmic reticulum *** research indicates that necroptosis is crucial to the pathophysiology of a number of neurological disorders and *** our review,we summarize the potential role of programmed cell death regulated by necroptosis in SCI based on its molecular and pathophysiological *** also summarize the targets of several necroptosis pathways,which provide a more reliable reference for the treatment of SCI.

关键词： Necroptosis spinal cord injury Pathological mechanisms Therapeutics

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Post-discharge follow-up of patients with spine trauma in the National spinal cord Injury Registry of Iran during the COVID-19 pandemic:Challenges and lessons learned

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Chinese Journal of Traumatology 2024年第3期27卷 173-179页

作者： Zahra Azadmanjir Moein Khormali Mohsen Sadeghi-Naini Vali Baigi Habibollah Pirnejad Mohammad Dashtkoohi Zahra Ghodsi Seyed Behnam Jazayeri Aidin Shakeri Mahdi Mohammadzadeh Laleh Bagheri Mohammad-Sajad Lotfi Salman Daliri Amir Azarhomayoun Homayoun Sadeghi-Bazargani Gerard O'reilly Vafa Rahimi-Movaghai Health Information Management Department School of Allied Medical SciencesTehran University of Medical SciencesTehranIran Sina Trauma and Surgery research Center Tehran University of Medical SciencesTehranIran Department of Neurosurgery Lorestan University of Medical SciencesKhoram-AbadIran Department of Epidemiology and Biostatistics School of Public HealthTehran University of Medical SciencesTehranIran Patient Safety research Center Clinical Rsearch institute Urma Universty of Medical SciencesUrmaIran Erasmus School of Health Policy&Management(ESHPM) Erasmus University RotterdamRoterdamthe Netherlands Brain and spinal cord Injury research Center Neuroscience InstituteTehran University of Medical SciencesTehranIran Students Scientifc research Center(SSRC) Tehran University of Medical SciencesTehranIran Department of Neurosurgery Arak University of Medical SciencesArakIran Trauma research Center Kashan University of Medical SciencesKashanIran Shahid Rahnemoun Hospital Shahid Sadoughi University of Medical SciencesYazdIran Trauma Nuring Rearch entre Faculty of Nursing and Midwifry Kahan Universty of Medical Sciences Kahan Iran Clinical research Development Unit Imam Hossein HospitalShahroud University of Medical SciencesShahroudIran research Center for Evidence Based Medicine Faculty of MedicineTabriz University of Medical SciencesTabrizIran Road Trafic Injury research Center Tabriz University of Medical SciencesTabrizIran School of Public Health and Preventive Medicine Monash UniversityMelbourneAustralia National Trauma research institute The AlfredMelbourneAustralia Department of Neurosurgery Shariati HospitalTehran University of Medical SciencesTehranIran Universal Scientific Education and research Network(USERN) TehranIran institute of Biochemistry and Biophysics University of TehranTehranIran

Purpose:The purpose of the National spinal cord Injury Registry of Iran(NSCIR-IR)is to create an infrastructure to assess the quality of care for spine trauma and in this study,we aim to investigate whether the NSCIR-IR successfully provides necessary post-discharge follow-up data for these ***:An observational prospective study was conducted from April 11,2021 to April 22,2022 in 8 centers enrolled in NSCIR-IR,respectively Arak,Rasht,Urmia,Shahroud,Yazd,Kashan,Tabriz,and *** were classified into 3 groups based on their need for care resources,respectively:(1)non-spinal cord injury(SCI)patients without surgery(group 1),(2)non-SCI patients with surgery(group 2),and(3)SCI patients(group 3).The assessment tool was a self-designed questionnaire to evaluate the care quality in 3 phases:pre-hospital,in-hospital,and *** data from the first 2 phases were collected through the *** post-hospital data were collected by conducting follow-up *** follow-ups were conducted for groups 1 and 2(non-SCI patients),while group 3(SCI patients)had a face-to-face *** study took place during the COVID-19 *** on age and time interval from injury to follow-up were expressed as mean±standard deviation(SD)and response rate and follow-up loss as a ***:Altogether 1538 telephone follow-up records related to 1292 patients were registered in the *** the total calls,918(71.05%)were related to successful follow-ups,but 38 cases died and thus were excluded from data *** the end,post-hospital data from 880 patients alive were *** success rate of follow-ups by telephone for groups 1 and 2 was 73.38%and 67.05%respectively,compared to 66.67%by face-to-face visits for group 3,which was very hard during the COVID-19 *** data completion rate after discharge ranged from 48%-100%,22%-100%and 29%-100%for groups ***:To improve patient accessibility,NSCIR-IR should take me

关键词： Follow-up studies spinal injuries spinal cord injuries COVID-19 NSCIR-IR

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Mapk7 deletion in chondrocytes causes vertebral defects by reducing MEF2C/PTEN/AKT signaling

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Genes & diseases 2024年第2期11卷 964-977页

作者： Chengzhi Wu Hengyu Liu Dongmei Zhong Xiaoming Yang Zhiheng Liao Yuyu Chen Shun Zhang Deying Su Baolin Zhang Chuan Li Liru Tian Caixia Xu Peiqiang Su Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China research Center for Translational Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Precision Medicine institute The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510080China Department of Orthopedics Renmin Hospital of Wuhan UniversityWuhanHubei 430060China Guangdong Provincial Key Laboratory of Proteomics and State Key Laboratory of Organ Failure research School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China

Mutation of the MAPK7 gene was related to human ***7 regulated the development of limb bones and skulls in ***,the role of MAPK7 in vertebral development is still *** this study,we constructed Col2a1-cre;Mapk7 f/f transgenic mouse model to delete Mapk7 in cartilage,which displayed kyphosis and ***,Mapk7 loss decreased MEF2C expression and thus activated PTEN to oppose PI3K/AKT signaling in vertebral growth plate chondrocytes,which impaired chondrocyte hypertrophy and attenuated vertebral *** vivo,systemic pharmacological activation of AKT rescued impaired chondrocyte hypertrophy and alleviated mouse vertebral defects caused by Mapk7 *** study firstly clarified the mechanism by which MAPK7 was involved in vertebral development,which might contribute to understanding the pathology of spinal deformity and provide a basis for the treatment of developmental disorders of the spine.

关键词： Chondrocyte hypertrophy Growth plate Kyphosis MAPK7 MEF2C Osteopenia PI3K/AKT PTEN

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