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| 1 | Molecular mechanosensors in osteocytes显示文摘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. | Lei Qin Wen Liu Huiling Cao Guozhi Xiao | 2020 | Bone Research2020，8，2： | 24 |
| 2 | Roles of mechanosensitive channel Piezo 1/2 proteins in skeleton and other tissues显示文摘Mechanotransduction is a fundamental ability that allows living organisms to receive and respond to physical signals from both the external and internal environments.The mechanotransduction process requires a range of special proteins termed mechanotransducers to convert mechanical forces into biochemical signals in cells.The Piezo proteins are mechanically activated nonselective cation channels and the largest plasma membrane ion channels reported thus far.The regulation of two family members,Piezol and Piezo2#has been reported to have essential functions in mechanosensation and transduction in different organs and tissues.Recently,the predominant contributions of the Piezo family were reported to occur in the skeletal system,especially in bone development and mechano-stimulated bone homeostasis.Here 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 mechanotransduction.In this review,we emphasize the diverse functions of Piezol and Piezo2 and related signaling pathways in osteoblast lineage cells and chondrocytes.We also summarize our current understanding of Piezo channel structures and the key findings about PIEZO gene mutations in human diseases. | Lei Qin Tailin He Sheng Chen Dazhi Yang Weihong Yi Huiling Cao Guozhi Xiao | 2021 | Bone Research2021，9，4： | 14 |
| 3 | Osteoarthritis:pathogenic signaling pathways and therapeutic targets显示文摘Osteoarthritis(OA)is a chronic degenerative joint disorder that leads to disability and affects more than 500 million population worldwide.OA 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 dysfunction.Currently,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 disease.Therefore,a better understanding of pathological signaling pathways and key molecules involved in OA pathogenesis is crucial for therapeutic target design and drug development.In this review,we first summarize the epidemiology of OA,including its prevalence,incidence and burdens,and OA risk factors.We 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 OA.In addition,the roles of factors associated with OA,including MMPs,ADAMTS/ADAMs,and PRG4,are discussed in detail.Finally,we provide updates on the current clinical therapies and clinical trials of biological treatments and drugs for OA.Research advances in basic knowledge of articular cartilage biology and OA pathogenesis will have a significant impact and translational value in developing OA therapeutic strategies. | Qing Yao Xiaohao Wu Chu Tao Weiyuan Gong Mingjue Chen Minghao Qu Yiming Zhong Tailin He Sheng Chen Guozhi Xiao | 2023 | Signal Transduction and Targeted Therapy2023，8，3： | 11 |
| 4 | Focal adhesion protein Kindlin-2 regulates bone homeostasis in mice显示文摘Our recent studies demonstrate that the focal adhesion protein Kindlin-2 is critical for chondrogenesis and early skeletal development. Here, we show that deleting Kindlin-2 from osteoblasts using the 2.3-kb mouse Col1 a1-Cre transgene minimally impacts bone mass in mice, but deleting Kindlin-2 using the 10-kb mouse Dmp1-Cre transgene, which targets osteocytes and mature osteoblasts, results in striking osteopenia in mice. Kindlin-2 loss reduces the osteoblastic population but increases the osteoclastic and adipocytic populations in the bone microenvironment. Kindlin-2 loss upregulates sclerostin in osteocytes,downregulates β-catenin in osteoblasts, and inhibits osteoblast formation and differentiation in vitro and in vivo. Upregulation ofβ-catenin in the mutant cells reverses the osteopenia induced by Kindlin-2 deficiency. Kindlin-2 loss additionally increases the expression of RANKL in osteocytes and increases osteoclast formation and bone resorption. Kindlin-2 deletion in osteocytes promotes osteoclast formation in osteocyte/bone marrow monocyte cocultures, which is significantly blocked by an anti-RANKLneutralizing antibody. Finally, Kindlin-2 loss increases osteocyte apoptosis and impairs osteocyte spreading and dendrite formation.Thus, we demonstrate an important role of Kindlin-2 in the regulation of bone homeostasis and provide a potential target for the treatment of metabolic bone diseases. | Huiling Cao Qinnan Yan Dong Wang Yumei Lai Bo Zhou Qi Zhang Wenfei Jin Simin Lin Yiming Lei Liting Ma Yuxi Guo Yishu Wang Yilin Wang Xiaochun Bai Chuanju Liu Jian QFeng Chuanyue Wu Di Chen Xu Cao Guozhi Xiao | 2020 | Bone Research2020，8，1： | 8 |
| 5 | Circular RNA circStag1 promotes bone regeneration by interacting with HuR显示文摘Postmenopausal osteoporosis is a common bone metabolic disorder characterized by deterioration of the bone microarchitecture,leading to an increased risk of fractures.Recently,circular RNAs(circ RNAs)have been demonstrated to play pivotal roles in regulating bone metabolism.However,the underlying functions of circ RNAs in bone metabolism in postmenopausal osteoporosis remain obscure.Here,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 osteoporosis.Overexpression of circ Stag1 significantly promoted the osteogenic capability of BMSCs.Mechanistically,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 BMSCs.Furthermore,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 rats.Collectively,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. | 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 | 2022 | Bone Research2022，10，3： | 7 |
| 6 | Kindlin-2 inhibits Nlrp3 inflammasome activation in nucleus pulposus to maintain homeostasis of the intervertebral disc显示文摘Intervertebral disc(IVD) degeneration(IVDD) is the main cause of low back pain with major social and economic burdens;however, its underlying molecular mechanisms remain poorly defined. Here we show that the focal adhesion protein Kindlin-2 is highly expressed in the nucleus pulposus(NP), but not in the anulus fibrosus and the cartilaginous endplates, in the IVD tissues. Expression of Kindlin-2 is drastically decreased in NP cells in aged mice and severe IVDD patients. Inducible deletion of Kindlin-2 in NP cells in adult mice causes spontaneous and striking IVDD-like phenotypes in lumbar IVDs and largely accelerates progression of coccygeal IVDD in the presence of abnormal mechanical stress. Kindlin-2 loss activates Nlrp3 inflammasome and stimulates expression of IL-1β in NP cells, which in turn downregulates Kindlin-2. This vicious cycle promotes extracellular matrix(ECM) catabolism and NP cell apoptosis. Furthermore, abnormal mechanical stress reduces expression of Kindlin-2, which exacerbates Nlrp3 inflammasome activation, cell apoptosis, and ECM catabolism in NP cells caused by Kindlin-2 deficiency. In vivo blocking Nlrp3 inflammasome activation prevents IVDD progression induced by Kindlin-2 loss and abnormal mechanical stress. Of translational significance, adeno-associated virus-mediated overexpression of Kindlin-2 inhibits ECM catabolism and cell apoptosis in primary human NP cells in vitro and alleviates coccygeal IVDD progression caused by mechanical stress in rat. Collectively, we establish critical roles of Kindlin-2 in inhibiting Nlrp3 inflammasome activation and maintaining integrity of the IVD homeostasis and define a novel target for the prevention and treatment of IVDD. | Sheng Chen Xiaohao Wu Yumei Lai Di Chen Xiaochun Bai Sheng Liu Yongchao Wu Mingjue Chen Yuxiao Lai Huiling Cao Zengwu Shao Guozhi Xiao | 2022 | Bone Research2022，10，1： | 6 |
| 7 | CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells显示文摘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. | Tingyu Wang Shan Li Dan Yi Guang-Qian Zhou Zhijie Chang Peter X.Ma Guozhi Xiao Di Chen | 2018 | Bone Research2018，6，2： | 5 |
| 8 | Current understanding of osteoarthritis pathogenesis and relevant new approaches显示文摘Osteoarthritis(OA)is the most common degenerative joint disease that causes painful swelling and permanent damage to the joints in the body.The molecular mechanisms of OA are currently unknown.OA is a heterogeneous disease that affects the entire joint,and multiple tissues are altered during OA development.To better understand the pathological mechanisms of OA,new approaches,methods,and techniques need to be used to understand OA pathogenesis.In 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 pain.We 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 tracing.Next,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 OA.Finally,our review highlights new directions on the role of the synovial lymphatic system in OA.An improved understanding of OA pathogenesis will aid in the development of more specific and effective therapeutic interventions for OA. | Liping Tong Huan Yu Xingyun Huang Jie Shen Guozhi Xiao Lin Chen Huaiyu Wang Lianping Xing Di Chen | 2022 | Bone Research2022，10，4： | 4 |
| 9 | The synergic effects of highly selective bimetallic Pt-Pd/SAPO-41 catalysts for the n-hexadecane hydroisomerization显示文摘The hydroisomerization of n-hexadecane over Pt-Pd bimetallic catalysts is an effective way to produce clean fuel oil.This work reports a useful preparation method of bimetallic bifunctional catalysts by a co-impregnation or sequential impregnation process.Furthermore,monometallic catalysts with loading either Pt or Pd are also prepared for comparison.The effects of the metal species and impregnation order on the characteristics and catalytic performance of the catalysts are investigated.The catalytic test results indicate that the maximum iso-hexadecane yield over different catalysts increases as follows:Pt/silicoaluminophosphate SAPO-41 | Guozhi Jia Chunmu Guo Wei Wang Xuefeng Bai Xiaomeng Wei Xiaofang Su Tong Li Linfei Xiao Wei Wu | 2021 | Frontiers of Chemical Science and Engineering2021，15，5： | 4 |
| 10 | Inhibition of Axinl in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation显示文摘Axinl is a negative regulator of β-catenin signaling and its role in osteoblast precursor cells remains undefined.In the present studies,we determined changes in postnatal bone growth by deletion of Axinl in osteoblast precursor cells and analyzed bone growth in newborn and postnatal Axin1 O5X mice and found that hypertrophic cartilage area was largely expanded in AxinlOSX KO mice.A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity of Axin1OSX KO mice.Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased,demonstrated by decreased TRAPpositive cell numbers,associated with reduction of MMP9-and cathepsin K-positive cell numbers in Axin1 O5X KO mice.OPG expression and the ratio of O p g to Rankl were significantly increased in osteoblasts of Axinl O5X KO mice.Osteoclast formation in primary bone marrow derived microphage(BMM)cells was significantly decreased when BMM cells were cultured with conditioned media(CM)collected from osteoblasts derived from Axin1OSX mice compared with BMM cells cultured with CM derived from WT mice.Thus,the loss of Axinl in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation,leading to delayed bone growth in postnatal Axin1°sx KO mice. | Bing Shu Yongjian Zhao Shitian Zhao Haobo Pan Rong Xie Dan Yi Ke Lu Junjie Yang Chunchun Xue Jian Huang Jing Wang Dongfeng Zhao Guozhi Xiao Yongjun Wang Di Chen | 2020 | Bone Research2020，8，3： | 3 |
| 11 | LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice显示文摘The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and adhesion.Here,we report that deleting Pinch1 in limb mesenchymal stem cells(MSCs)and Pinch2 globally(double knockout;dKO)in mice causes severe chondrodysplasia,while single mutant mice do not display marked defects.Pinch deletion decreases chondrocyte proliferation,accelerates cell differentiation and disrupts column formation.Pinch loss drastically reduces Smad2/3 protein expression in proliferative zone(PZ)chondrocytes and increases Runx2 and Col10a1 expression in both PZ and hypertrophic zone(HZ)chondrocytes.Pinch loss increases sclerostin and Rankl expression in HZ chondrocytes,reduces bone formation,and increases bone resorption,leading to low bone mass.In vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of chondrocytes.Through its C-terminal region,Pinch1 interacts with Smad2/3 proteins.Pinch loss increases Smad2/3 ubiquitination and degradation in primary bone marrow stromal cells(BMSCs).Pinch loss reduces TGF-β-induced Smad2/3 phosphorylation and nuclear localization in primary BMSCs.Interestingly,compared to those from single mutant mice,BMSCs from dKO mice express dramatically lower protein levels ofβ-catenin and Yap1/Taz and display reduced osteogenic but increased adipogenic differentiation capacity.Finally,ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb shortening.Collectively,our findings demonstrate critical roles for Pinch1/2 and a functional redundancy of both factors in the control of chondrogenesis and bone mass through distinct mechanisms. | Yiming Lei Xuekun Fu Pengyu Li Sixiong Lin Qinnan Yan Yumei Lai Xin Liu Yishu Wang Xiaochun Bai Chuanju Liu Di Chen Xuenong Zou Xu Cao Huiling Cao Guozhi Xiao | 2020 | Bone Research2020，8，4： | 2 |
| 12 | Regulation of the osteoblast -specific transcription factor,Runx2 responsiveness to multiple signal transduction pathways显示文摘 | Renny T Franceschi Guozhi Xiao | 2003 | Journal of Cellular Biochemistry2003，88，： | 1 |
| 13 | A Cerenkov generator with coaxial slow wave structure显示文摘 | Liu Guozhi Xiao Renzhen Chen Changhua | 2008 | J Appl Phys2008，103，09： | 1 |
| 14 | Starting current of coaxial relative backward wave oscillator显示文摘 | Teng Yan Xiao Renzhen Liu Guozhi | 2010 | Phys Plasmas2010，17，06： | 1 |
| 15 | Ortho-(1-phenylvinyl)benzyl glycosides: Ether-type glycosyl donors for the efficient synthesis of both O-glycosides and nucleosides显示文摘Both O-glycosides and nucleosides are essential biomolecules with important roles in a variety of biological processes.Chemical synthesis of both O-glycosides and nucleosides is a scalable and reliable method to develop new therapeutic agents and decipher their functions.However,the efficient synthesis of both O-glycosides and nucleosides remains one of long-standing challenges in chemical synthesis.In particular,ether-type glycosyl donors are rarely developed to achieve the efficient synthesis of both O-glycosides and nucleosides due to the stronger conditions required for breaking of the glycosidic C–O bond.Here we report that ortho-(1-phenylvinyl)benzyl glycosides are new ether-type donors for efficient synthesis of both O-glycosides and nucleosides under mild reaction conditions.This glycosylation method enables glycosylation with both alcoholic acceptors and nucleobases with a variety of reactive functionalities.Furthermore,the latent-active synthesis of glycans and the efficient synthesis of nucleosides antibiotics have also been successfully demonstrated in the current glycosylation protocol,thereby representing an important step toward streamlining the chemical synthesis of both O-glycosides and nucleosides. | Penghua Li Haiqing He Lili Xu Yingying Huang Zixi Chen Yunqin Zhang Rui Yang Guozhi Xiao | 2020 | Green Synthesis and Catalysis2020，1，2： | 1 |
| 16 | Total Synthesis of Starfish Cyclic Steroid Glycosides.Part 2,Model Synthesis via Intramolecular Etherification显示文摘Comprehensive Summary Sepositoside A(1)is a prototypical cyclic steroid glycoside bearing a hybrid 16-membered ring composed of the steroid skeleton and a 1,2-trans-linked trisaccharide.Herein,we report an expedient access toward two simplified analogues,in which the strained 16-membered ring is constructed via Au(I)-catalyzed intramolecular addition of alcohol to epoxide.A similar macroetherification in relevant steroid trisaccharides has been intensively examined,however,failed to furnish the macrocyclic skeleton of Sepositoside A. | Youxi Chen Guozhi Xiao Dapeng Zhu Biao Yu | 2023 | Chinese Journal of Chemistry2023，41，8： | 1 |
| 17 | Bone Morphogenetic Proteins, Extracellular Matrix, and Mitogen-Activated Protein Kinase Signaling Pathways Are Required for Osteoblast-Specific Gene Expression and Differentiation in MC3T3- E1 Cells显示文摘 | GUOZHI XIAO RAJARAM GOPALAKRISHNAN DI JIANG | 2002 | JBMR2002，17，1： | 1 |
| 18 | MAPK Pathways Activate and Phosphorylate the Osteoblast-specific Transcription Factor,cbfal显示文摘 | Guozhi Xiao Di Jiang Peedikayil Thomas | 2000 | J Bio Chem2000，275，6： | 1 |
| 19 | A Cerenkov generator with coaxial slow wave structure显示文摘 | Liu Guozhi Xiao Renzhen Chen Changhua | 2008 | J Appl Phys2008，103，09： | 1 |
| 20 | A ceren- kov generator with coaxial slow wave structure 显示文摘 | Liu Guozhi Xiao Renzhe Chen Changhua | 2008 | Journal of Applied Physics2008，103，9： | 1 |
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