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Stereoselectiveα-Glycosylation with GlcN_(3)Donors Enabled Collective Syntheses of Acinetobacter baumannii Capsular Polysaccharides K43,K47 and K88 Repeating Units

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Chinese Journal of Chemistry 2024年第14期42卷 1593-1598页

作者： Kunxiu Shou Shanshan Liu Yunqin Zhang guozhi xiao State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyUniversity of Chinese Academy of SciencesChinese Academy of SciencesKunmingYunnan650201 China

Collective syntheses of *** CPS K43,K47 and K88 repeating units have been accomplished via a newα-glycosylation method with GlcN_(3) as donors,which features:1)mild reaction conditions,2)good to high yields,3)excellent *** synthetic route also highlights an orthogonal one-pot coupling strategy on the basis of glycosyl ortho-(1-phenylvinyl)benzoates for stereoselective constructions of both 1,2-trans and 1,2-cis glycosidic bonds,precluding the issues of aglycone transfer.

关键词： A baumanni CPS α-Glycosylation method One-pot glycosylation 1,2-GlcN bonds Glycosyl ortho-(1-phenylvinyl)benzoates Carbohydrates Oligosaccharides Total synthesis

Molecular mechanosensors in osteocytes

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Bone Research 2020年第2期8卷 115-138页

作者： Lei Qin Wen Liu Huiling Cao guozhi xiao Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research Shenzhen Key Laboratory of Cell Microenvironmentand School of MedicineSouthern University of Science and TechnologyShenzhen 518055China

Osteocytes, the most abundant and long-lived cells in bone, are the master regulators of bone remodeling. In addition to their functions in endocrine regulation and calcium and phosphate metabolism, osteocytes are the major responsive cells in force adaptation due to mechanical stimulation. Mechanically induced bone formation and adaptation, disuse-induced bone loss and skeletal fragility are mediated by osteocytes, which sense local mechanical cues and respond to these cues in both direct and indirect ways. The mechanotransduction process in osteocytes is a complex but exquisite regulatory process between cells and their environment, between neighboring cells, and between different functional mechanosensors in individual cells. Over the past two decades, great efforts have focused on finding various mechanosensors in osteocytes that transmit extracellular mechanical signals into osteocytes and regulate responsive gene expression. The osteocyte cytoskeleton, dendritic processes, Integrin-based focal adhesions, connexin-based intercellular junctions, primary cilium, ion channels, and extracellular matrix are the major mechanosensors in osteocytes reported so far with evidence from both in vitro and in vitro studies. This review aims to give a systematic introduction to osteocyte mechanobiology, provide details of osteocyte mechanosensors, and discuss the roles of osteocyte mechanosensitive signaling pathways in the regulation of bone homeostasis.

关键词： cytes mec metabolism

Roles of mechanosensitive channel Piezo 1/2 proteins in skeleton and other tissues

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Bone Research 2021年第4期9卷 456-472页

作者： Lei Qin Tailin He Sheng Chen Dazhi Yang Weihong Yi Huiling Cao guozhi xiao Department of Orthopedics Huazhong University of Science and Technology Union Shenzhen HospitalShenzhenGuangdongChina Department of Biochemistry School of MedicineGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentSouthern University of Science and TechnologyShenzhenGuangdongChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina

Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal *** mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in *** Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus *** regulation of two family members,Piezol and Piezo2#has been reported to have essential functions in mechanosensation and transduction in different organs and ***,the predominant contributions of the Piezo family were reported to occur in the skeletal system,especially in bone development and mechano-stimulated bone *** we review current studies focused on the tissue-specific functions of Piezol and Piezo2 in various backgrounds with special highlights on their importance in regulating skeletal cell *** this review,we emphasize the diverse functions of Piezol and Piezo2 and related signaling pathways in osteoblast lineage cells and *** also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases.

关键词： mec sensation organs

Bone marrow adipoq+ cell population controls bone mass via sclerostin in mice

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3570-3572页

作者： Huanqing Gao Yiming Zhong Sixiong Lin Qinnan Yan Xuenong Zou guozhi xiao Department of Biochemistry School of MedicineGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchShenzhen Key Laboratory of Cell MicroenvironmentSouthern University of Science and TechnologyShenzhen 518055China State Key Laboratory of Genetic Engineering and School of Life Sciences Fudan UniversityShanghai 200438China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology Department of Spinal SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China

Dear editor,The comorbidity of obesity and osteoporosis illustrates the communication and coordination of adipose and bone *** and adiponectin derived from adipocytes regulate osteoblast formation and function to impact bone mass through direct and indirect mechanisms.1 It is known that bone marrow adipocytes(BMA)can control bone mass by modulating the bone morphogenetic protein(BMP)and other signaling *** can secret soluble factors,which impact osteoblasts,osteoclasts,and osteocytes.2 Sclerostin is a potent inhibitor of bone acquisition that antagonizes Wnt/β-catenin signaling.

关键词： marrow osteoporosis obesity

Roles of focal adhesion proteins in skeleton and diseases

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Acta Pharmaceutica Sinica B 2023年第3期13卷 998-1013页

作者： Sheng Chen Tailin He Yiming Zhong Mingjue Chen Qing Yao Di Chen Zengwu Shao guozhi xiao Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of Biochemistry School of MedicineShenzhen Key Laboratory of Cell MicroenvironmentGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchSouthern University of Science and TechnologyShenzhen 518055China Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

The skeletal system,which contains bones,joints,tendons,ligaments and other elements,plays a wide variety of roles in body shaping,support and movement,protection of internal organs,production of blood cells and regulation of calcium and phosphate *** prevalence of skeletal diseases and disorders,such as osteoporosis and bone fracture,osteoarthritis,rheumatoid arthritis,and intervertebral disc degeneration,increases with age,causing pain and loss of mobility and creating a huge social and economic burden *** adhesions(FAs)are macromolecular assemblies that are composed of the extracellular matrix(ECM),integrins,intracellular cytoskeleton and other proteins,including kindlin,talin,vinculin,paxillin,pinch,Src,focal adhesion kinase(FAK)and integrin-linked protein kinase(ILK)and other *** acts as a mechanical linkage connecting the ECM and cytoskeleton and plays a key role in mediating cell–environment communications and modulates important processes,such as cell attachment,spreading,migration,differentiation and mechanotransduction,in different cells in skeletal system by impacting distinct outside-in and inside-out signaling *** review aims to integrate the up-to-date knowledge of the roles of FA proteins in the health and disease of skeletal system and focuses on the specific molecular mechanisms and underlying therapeutic targets for skeletal diseases.

关键词： Focal adhesion Skeleton Mechanotransduction Signal transduction Integrin Cartilage Intervertebral disc Skeletal diseases

Deletion of Axin1 in aggrecan-expressing cells leads to growth plate cartilage defects in adult mice

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Genes & Diseases 2024年第4期11卷 149-151页

作者： Dan Yi Hongting Jin William W.Lu Chunxiang Zhang guozhi xiao Liping Tonag Di Chen Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China PFaculty of Pharmaceutical Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China The First College of Clinical Medicine Zhejiang Chinese Medical UniversityHangzhouZhejiang 310053China Department of Cardiology Basic Medicine Innovation Centerfor Cardiometabolic Diseases of Ministry of EducationInstitute of Cardiovascular ResearchThe Affiliated HospitalSouthwest Medical UniversityLuzhouSichuan 646000China School of Medicine Southern University of Science and TechnologyShenzhenGuangdong 518055China

In mammals,skeletal bone development begins at hyaline cartilage formation at the early embryonic stage.1Then osteoblasts from the periosteum,which are distributed surrounding the hyaline cartilage,build up compact bone to formdiaphysis and spongy bone known as primary ossification center.1 Next,osteoclasts from the hematopoietic system destroy spongy bone to generate a medullary cavity.

关键词： cartilage skeletal medullary

Current understanding of osteoarthritis pathogenesis and relevant new approaches

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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

CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells

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Bone Research 2018年第2期6卷 145-154页

作者： Tingyu Wang Shan Li Dan Yi Guang-Qian Zhou Zhijie Chang Peter X.Ma guozhi xiao Di Chen Department of Pharmacy Shanghai Ninth People's Hospital Shanghai Jiao Tong University School of Medicine Department of Orthopedic Surgery Rush University Medical Center Department of Medical Cell Biology and Genetics Shenzhen Key Laboratory and the Center for Anti-Ageing and Regenerative Medicine Shenzhen University Medical School State Key Laboratory of Biomembrane and Membrane Biotechnology Tsinghua University School of Medicine Department of Biologic and Materials Science University of Michigan

Carboxyl terminus of Hsp70-interacting protein（CHIP or STUB1） is an E3 ligase and regulates the stability of several proteins which are involved in different cellular functions. Our previous studies demonstrated that Chip deficient mice display bone loss phenotype due to increased osteoclast formation through enhancing TRAF6 activity in osteoclasts. In this study we provide novel evidence about the function of CHIP. We found that osteoblast differentiation and bone formation were also decreased in Chip KO mice. In bone marrow stromal（BMS） cells derived from Chip^-/- mice, expression of a panel of osteoblast marker genes was significantly decreased. ALP activity and mineralized bone matrix formation were also reduced in Chip-deficient BMS cells. We also found that in addition to the regulation of TRAF6, CHIP also inhibits TNFα-induced NF-κB signaling through promoting TRAF2 and TRAF5 degradation. Specific deletion of Chip in BMS cells downregulated expression of osteoblast marker genes which could be reversed by the addition of NF-κB inhibitor. These results demonstrate that the osteopenic phenotype observed in Chip^-/- mice was due to the combination of increased osteoclast formation and decreased osteoblast differentiation. Taken together, our findings indicate a significant role of CHIP in bone remodeling.

关键词： CHIP regulates bone mass targeting multiple TRAF family members marrow stromal cells

Osteoarthritis:pathogenic signaling pathways and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第3期8卷 932-962页

作者： Qing Yao xiaohao Wu Chu Tao Weiyuan Gong Mingjue Chen Minghao Qu Yiming Zhong Tailin He Sheng Chen guozhi xiao Department of Biochemistry School of MedicineShenzhen Key Laboratory of Cell MicroenvironmentGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease ResearchSouthern University of Science and TechnologyShenzhen 518055China Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population *** was believed to be caused by the wearing and tearing of articular cartilage,but it is now more commonly referred to as a chronic whole-joint disorder that is initiated with biochemical and cellular alterations in the synovial joint tissues,which leads to the histological and structural changes of the joint and ends up with the whole tissue ***,there is no cure for OA,partly due to a lack of comprehensive understanding of the pathological mechanism of the initiation and progression of the ***,a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug *** this review,we first summarize the epidemiology of OA,including its prevalence,incidence and burdens,and OA risk *** then focus on the roles and regulation of the pathological signaling pathways,such as Wnt/β-catenin,NF-κB,focal adhesion,HIFs,TGFβ/ΒΜP and FGF signaling pathways,and key regulators AMPK,mTOR,and RUNX2 in the onset and development of *** addition,the roles of factors associated with OA,including MMPs,ADAMTS/ADAMs,and PRG4,are discussed in ***,we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for *** advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies.

关键词： therapeutic Osteoarthritis epidemiology