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The role of GPCRs in bone diseases and dysfunctions

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Bone Research 2019年第2期7卷 138-156页

作者： Jian Luo Peng Sun Stefan Siwko Mingyao Liu jianru xiao East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology Shanghai Key Laboratory of Regulatory BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal University200241 ShanghaiChina The Key Laboratory of Adolescent Health Assessment and Exercise Intervention of the Ministry of Education East China Normal University200241 ShanghaiChina Department of Molecular and Cellular Medicine Institute of Biosciences and TechnologyTexas A&M University Health Science CenterHoustonTX 77030USA East China Normal University and Shanghai Changzheng Hospital Joint Research Center for Orthopedic Oncology Department of Orthopedic OncologyShanghai Changzheng HospitalSecond Military Medical UniversityShanghaiChina

The superfamily of G protein-coupled receptors (GPCRs) contains immense structural and functional diversity and mediates a myriad of biological processes upon activation by various extracellular *** roles of GPCRs have been established in bone development,remodeling,and *** human GPCR mutations impair bone development or metabolism,resulting in *** we summarize the disease phenotypes and dysfunctions caused by GPCR gene mutations in humans as well as by deletion in *** date,92 receptors (5 glutamate family,67 rhodopsin family,5 adhesion,4 frizzled/taste2 family,5 secretin family,and 6 other 7TM receptors) have been associated with bone diseases and dysfunctions (36 in humans and 72 in animals).By analyzing data from these 92 GPCRs,we found that mutation or deletion of different individual GPCRs could induce similar bone diseases or dysfunctions,and the same individual GPCR mutation or deletion could induce different bone diseases or dysfunctions in different populations or animal *** from human diseases or dysfunctions identified 19 genes whose mutation was associated with human BMD:9 genes each for human height and osteoporosis;4 genes each for human osteoarthritis (OA) and fracture risk;and 2 genes each for adolescent idiopathic scoliosis (AIS),periodontitis,osteosarcoma growth,and tooth *** from gene knockout animals found 40 GPCRs whose deficiency reduced bone mass,while deficiency of 22 GPCRs increased bone mass and BMD;deficiency of 8 GPCRs reduced body length,while 5 mice had reduced femur size upon GPCR ***,deficiency in 6 GPCRs induced osteoporosis;4 induced osteoarthritis;3 delayed fracture healing;3 reduced arthritis severity;and reduced bone strength,increased bone strength,and increased cortical thickness were each observed in 2 GPCR-deficiency *** ever-expanding number of GPCR mutation-associated diseases warrants accelerated molecular analysis,population

关键词： role GPCRs diseases and dysfunctions

Breaking the vicious cycle between tumor cell proliferation and bone resorption by chloroquine-loaded and bone-targeted polydopamine nanoparticles

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Science China Materials 2021年第2期64卷 474-487页

作者： Yitong Wang Hui Chen Kaili Lin Ting Ying Quan Huang xiaopan Cai jianru xiao Qiang Zhang Yiyun Cheng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai200241China Department of Oral&Cranio-Maxillofacial Surgery Shanghai Ninth People’s HospitalCollege of StomatologyShanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of Stomatology&Shanghai Research Institute of StomatologyShanghai200011China College of Life and Environmental Sciences Shanghai Normal UniversityShanghai200234China Department of Orthopedics Oncology Changzheng Hospitalthe Second Military Medical UniversityShanghai200003China South China Advanced Institute for Soft Matter Science and Technology School of Molecular Science and EngineeringSouth China University of TechnologyGuangzhou510640China

The vicious cycle between tumor cell proliferation and bone resorption remarkably elevates the progression and metastasis of bone ***,we fabricated polyethylene glycol-conjugated alendronate-functionalized and chloroquine(CQ)-loaded polydopamine nanoparticles(PPA/CQ)for efficient treatment of bone tumors via breaking the vicious *** nanoparticles were efficiently accumulated to the bone tissues,especially the osteolytic lesions around *** released from PPA/CQ inhibited osteoclastogenesis via preventing the degradation of tumor necrosis factor(TNF)receptor-associated receptor 3 to attenuate the osteolysis in bone *** the other hand,CQ blocked the autophagy in cancer cells,resulting in improved photothermal killing of cancer ***,the in vivo experiment revealed that PPA/CQ-associated treatment efficiently inhibited both tumor growth and *** work suggests that autophagy inhibition-associated photothermal therapy could be a promising strategy for treating malignant bone tumors.

关键词： targeted nanoparticles cancer therapy multifunctional nanoparticles drug delivery bone targeting

Mutant p53 promotes cell spreading and migration via ARHGAP44

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Science China(Life Sciences) 2017年第9期60卷 1019-1029页

作者： Jinjin Xu Jian Jiao Wei Xu Lei Ji Dongjie Jiang Shaofang Xie Syeda Kubra xiaotao Li Junjiang Fu jianru xiao Bianhong Zhang Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal University Department of Orthopedic Oncology Changzheng Hospitalthe Second Military Medical University Key Laboratory of Epigenetics and Oncology The Research Center for Preclinical MedicineSouthwest Medical University

The tumor suppressor p53 protein is either lost or mutated in about half of all human *** of p53 function is well known to influence cell spreading,migration and *** expression of mutant p53 is not equivalent to p53 loss,mutant p53 can acquire new functions to drive cell spreading and migration via different *** our study,we found that mutant p53 significantly increased cell spreading and migration when comparing with p53-null ***-Seq analysis suggested that Rho GTPase activating protein 44(ARHGAP44) is a new target of mutant p53,which suppressed AKHGAP44 ***44 has GAP activity and catalyze GTP hydrolysis on *** level of GTP-Cdc42 was correlated with increase expression of mutant p53 and reduced ***,wt-ARHGAP44 but not mutant ARHGAP44(R291A) suppressed mutant p53 mediated cell spreading and *** analysis indicated lower expression of ARHGAP44 in lung carcinoma compared with normal tissues,which was verified by RT-qPCR using specimens from *** interestingly,ARHGAP44 mRNA level was lower in tumors with mutant p53 than those with normal ***,our results disclose a new mechanism by which mutant p53 stimulates cell spreading and migration.

关键词： mutant p53 novel function of ARHGAP44 cell spreading cell migration cancer new mechanism

Follow-up experience and surgical interventions of chordomas in the cervical spine

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Follow-up experience and surgical interventions of chordomas...

Construction of metastatic spinal cancer tissue microarrays

中华医学会第八届骨科学术会议暨第一届国际COA学术大会

作者： Cao Dong Ma Junming and xiao jianru

＜正＞Objective: To retrospectively study the characteristics and surgical interventions of chordomas in the cervical spine. Method: All the clinical data, radiographic studies and pathological results of 8 cases of c...

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Journal of Medical Colleges of PLA(China) 2009年第3期24卷 176-182页

作者： Yang Xinghai Chen Huajiang xiao jianru Yuan Wen Jia Lianshun Department of Orthopedics Changzheng Hospital Second Military Medial University Shanghai 200003 China

Objective： To explore the construction of metastatic spinal cancer （MSC） tissue microarrays and validate its value in immunohistochemical study of MSC. Methods： Paraffin-embedded specimens from 71 MSC cases and 6 primary tumor cases were selected as donor blocks and prepared into MSC tissue microarrays by tissue array arrangement, the steps of which included location, punching, sampling, sample seeding, and re-diagnosis by hematoxylin-eosin （HE） as well as MMP-9 and MMP-14 immunohistoehemical staining. Results： The MSC tissue microarrays thus constructed were intact and craekless, containing 154 complete and well arranged microarray points. None of the sectioned tissue microarrays was lost, and the results of HE staining was consistent with the primary pathologic diagnoses. Immunohistochemical staining was also good without non-specific or marginal effect. Conclusion： The MSC tissue microarrays have a high value in the immunohistochemical study of MSC.

关键词： Spine Metastases Tissue microarray

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories

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Bone Research 2023年第1期11卷 148-162页

作者： Hao Zhang Ting Wang Haiyi Gong Runyi Jiang Wang Zhou Haitao Sun Runzhi Huang Yao Wang Zhipeng Wu Wei Xu Zhenxi Li Quan Huang xiaopan Cai Zaijun Lin Jinbo Hu Qi Jia Chen Ye Haifeng Wei jianru xiao Department of Orthopedic Oncology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai200003China Musculoskeletal Laboratory Institute of BiotechnologyUniversity of Shanghai for Science and TechnologyShanghai200093China Department of Orthopedics Naval Medical Center of CPLANaval Medical UniversityShanghai200052China Peking-Tsinghua Center for Life Sciences Tsinghua UniversityBeijing100084China Division of Spine Department of OrthopedicsTongji Hospital Affiliated to Tongji University School of MedicineShanghai200065China

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer ***,the highly complex cell origin involved in osteosarcoma(OS)limits the utility of traditional bulk RNA sequencing for OS ***-cell RNA sequencing(sc RNA-seq)holds great promise for identifying cell ***,this technique has rarely been used in the study of tumor *** analyzing sc RNA-seq data for six conventional OS and nine cancellous bone(CB)samples,we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell(CSC)-like subset,which allowed us to classify OS samples into three *** classification model was further examined using the TARGET *** subgroup of OS had different prognoses and possible drug sensitivities,and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS *** addition,we verified the classification model through IHC staining in 138 OS samples,revealing a worse prognosis for Group B ***,we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of *** findings provide a novel subclassification method based on sc RNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

关键词： osteosarcoma holds classify

Pericytes may facilitate SARS-CoV-2 entry into the nervous system

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Journal of Bio-X Research 2023年第1期6卷 23-36页

作者： Zijian Kang Jing Wang Tong Meng Hao Zhang Da Xu Haiyi Gong Zhenyan Chang Zifu Li Xingang Cui jianru xiao Adnan I.Qureshi Wang Zhou Jianmin Liu Huji Xua Department of Rheumatology and Immunology Changzheng Hospital Department of Neurosurgery Changhai HospitalSecond Military Medical University Division of Spine Department of OrthopedicsShanghai General HospitalSchool of MedicineShanghai Jiaotong University Tongji University Cancer Center School of MedicineTongji University Department of Orthopaedic Oncology Changzheng Hospital Department of Urology The Third Affiliated HospitalSecond Military Medical University Department of Pathology Shanghai Tenth People’s HospitalTongji University School of MedicineShanghaiChina Zeenat Qureshi Stroke Institutes and University of Missouri ColumbiaMOUSA Peking-Tsinghua Center for Life Sciences School of Medicine Tsinghua UniversityBeijingChina

Objective:Although the neurological and olfactory symptoms of coronavirus disease 2019 have been identified,the neurotropic properties of the causative virus,severe acute respiratory syndrome-associated coronavirus 2(SARS-CoV-2),remain *** sought to identify the susceptible cell types and potential routes of SARS-CoV-2 entry into the central nervous system,olfactory system,and respiratory ***:We collected single-cell RNA data from normal brain and nasal epithelium specimens,along with bronchial,tracheal,and lung specimens in public *** susceptible cell types that express SARS-CoV-2 entry genes were identified using single-cell RNA sequencing and the expression of the key genes at protein levels was verified by *** compared the coexpression patterns of the entry receptor angiotensin-converting enzyme 2(ACE2)and the spike protein priming enzyme transmembrane serine protease(TMPRSS)/cathepsin L among the ***:The SARS-CoV-2 entry receptor ACE2 and the spike protein priming enzyme TMPRSS/cathepsin L were coexpressed by pericytes in brain tissue;this coexpression was confirmed by *** the nasal epithelium,ciliated cells and sustentacular cells exhibited strong coexpression of ACE2 and *** and glia in the brain and nasal epithelium did not exhibit coexpression of ACE2 and ***,coexpression was present in ciliated cells,vascular smooth muscle cells,and fibroblasts in tracheal tissue;ciliated cells and goblet cells in bronchial tissue;and alveolar epithelium type 1 cells,AT2 cells,and ciliated cells in lung ***:Neurological symptoms in patients with coronavirus disease 2019 could be associated with SARS-CoV-2 invasion across the blood-brain barrier via ***,SARS-CoV-2-induced olfactory disorders could be the result of localized cell damage in the nasal epithelium.

关键词： ACE2 coronavirus disease 2019 SARS-CoV-2 single-cell RNA sequencing TMPRSS2