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LIM domain proteins Pinch1/2 regulate chondrogenesis and bone mass in mice

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Bone Research 2020年第4期8卷 416-428页

作者： 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 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 Department of Spine Surgery Orthopedic Research InstituteThe First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and TraumatologyGuangzhou 510080China Department of Orthopedic Surgery Rush University Medical CenterChicagoIL 60612USA Department of Cell Biology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Orthopedic Surgery New York University School of MedicineNew YorkNY 10003USA Department of Cell Biology New York University School of MedicineNew YorkNY 10016USA Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Orthopedic Surgery The Johns Hopkins UniversityBaltimoreMD 21205USA

The LIM domain-containing proteins Pinch1/2 regulate integrin activation and cell–extracellular matrix interaction and ***,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 *** deletion decreases chondrocyte proliferation,accelerates cell differentiation and disrupts column *** 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)*** loss increases sclerostin and Rankl expression in HZ chondrocytes,reduces bone formation,and increases bone resorption,leading to low bone *** vitro studies revealed that Pinch1 and Smad2/3 colocalize in the nuclei of *** its C-terminal region,Pinch1 interacts with Smad2/3 *** 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 ***,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 ***,ablating Pinch1 in chondrocytes and Pinch2 globally causes severe osteopenia with subtle limb ***,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.

关键词： Smad2/3 globally mass

Kindlin-2 regulates skeletal homeostasis by modulating PTH1R in mice

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Signal Transduction and Targeted Therapy 2021年第1期6卷 131-143页

作者： Xuekun Fu Bo Zhou Qinnan Yan Chu Tao Lei Qin Xiaohao Wu sixiong lin Sheng Chen Yumei Lai Xuenong Zou Zengwu Shao Meiqing Wang Di Chen Wenfei Jin Youqiang Song Huiling Cao Ge Zhang Guozhi Xiao School of Medicine Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Researchand Shenzhen Key Laboratory of Cell MicroenvironmentSouthern University of Science and Technology1088 Xue Yuan Road518055 ShenzhenGuangdongChina Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases School of Chinese MedicineHong Kong Baptist University999077 Hong KongSARChina Department of Biology Southern University of Science and Technology518055 ShenzhenChina School of Biomedical Sciences University of Hong Kong21 Sassoon RoadHong KongChina Department of Spine Surgery Orthopedic Research InstituteThe First Affiliated Hospital of Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Orthopedics and Traumatology510080 GuangzhouChina Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and Technology430022 WuhanChina Department of Orthopedic Surgery Rush University Medical CenterChicagoIL 60612USA State Key Laboratory of Military Stomatology National Clinical Research Center for Oral DiseasesShanxi International Joint Research Center for Oral DiseasesDepartment of Oral Anatomy and Physiology and TMDSchool of Stomatologythe Fourth Military Medical University145 Changle West RoadXi’anChina Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences518055 ShenzhenChina

In vertebrates,the type 1 parathyroid hormone receptor(PTH1R)is a critical regulator of skeletal development and homeostasis;however,how it is modulated is incompletely *** we report that deleting Kindlin-2 in osteoblastic cells using the mouse 10-kb Dmp1-Cre largely neutralizes the intermittent PTH-stimulated increasing of bone volume fraction and bone mineral density by impairing both osteoblast and osteoclast formation in murine adult ***-cell profiling reveals that Kindlin-2 loss increases the proportion of osteoblasts,but not mesenchymal stem cells,chondrocytes and fibroblasts,in non-hematopoietic bone marrow cells,with concomitant depletion of osteoblasts on the bone surfaces,especially those stimulated by ***,haploinsufficiency of Kindlin-2 and Pth1r genes,but not that of either gene,in mice significantly decreases basal and,to a larger extent,PTH-stimulated bone mass,supporting the notion that both factors function in the same genetic ***,Kindlin-2 interacts with the C-terminal cytoplasmic domain of PTH1R via aa 474–475 and Gsα.Kindlin-2 loss suppresses PTH induction of cAMP production and CREB phosphorylation in cultured osteoblasts and in ***,PTH promotes Kindlin-2 expression in vitro and in vivo,thus creating a positive feedback regulatory ***,estrogen deficiency induced by ovariectomy drastically decreases expression of Kindlin-2 protein in osteocytes embedded in the bone matrix and Kindlin-2 loss essentially abolishes the PTH anabolic activity in bone in ovariectomized ***,we demonstrate that Kindlin-2 functions as an intrinsic component of the PTH1R signaling pathway in osteoblastic cells to regulate bone mass accrual and homeostasis.

关键词： homeostasis Kindlin skeletal

Simultaneous incorporation of PTH(1-34) and nano-hydroxyapatite into Chitosan/Alginate Hydrogels for efficient bone regeneration

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Bioactive Materials 2021年第6期6卷 1839-1851页

作者： Zhiyuan Zou Le Wang Zhifei Zhou Qing Sun Delong Liu Yan Chen Hao Hu Yu Cai sixiong lin Zhengran Yu Bizhi Tan Wei Guo Zemin ling Xuenong Zou Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology Department of Spine SurgeryThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Key Laboratory of Functional Polymer Materials Ministry of EducationInstitute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin 300071China Department of Pathology Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityGuangzhou 510120China Department of Orthopaedics Hunan Provincial People’s HospitalChangsha 410002China Institute of Chemical Biology Shenzhen Bay LaboratoryShenzhen518132China

Tissue regeneration based on the utilization of artificial soft materials is considered a promising treatment for bone-related ***,we report cranial bone regeneration promoted by hydrogels that contain parathyroid hormone(PTH)peptide PTH(1-34)and nano-hydroxyapatite(nHAP).A combination of the positively charged natural polymer chitosan(CS)and negatively charged sodium alginate led to the formation of hydrogels with porous structures,as shown by scanning electron *** characterizations revealed that the mechanical properties of the hydrogels were almost maintained upon the addition of nHAP and PTH(1-34).In vitro experiments showed that the hydrogel containing nHAP and PTH(1-34)exhibited strong biocompatibility and facilitated osteogenic differentiation of rat bone marrow mesenchymal stem cells(rBMSCs)via the Notch signaling pathway,as shown by the upregulated expression of osteogenic-related *** found that increasing the content of PTH(1-34)in the hydrogels resulted in enhanced osteogenic differentiation of *** of the complex hydrogel into a rat cranial defect model led to efficient bone regeneration compared to the rats treated with the hydrogel alone or with nHAP,indicating the simultaneous therapeutic effect of nHAP and PTH during the treatment *** the in vitro and in vivo results demonstrated that simultaneously incorporating nHAP and PTH into hydrogels shows promise for bone regeneration,suggesting a new strategy for tissue engineering and regeneration in the future.

关键词： Parathyroid hormone Hydrogels Bone regeneration Tissue engineering

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泉州金屿大桥公轨共线过江断面组合模式选择

福建建筑 2018年第4期 83-87页

作者：林嗣雄福州市规划设计研究院福建福州350108

以泉州金屿大桥为研究实例,根据公路和轨道所处位置及作用,提出平层、双层和分离3大形式,6种共建设计模式。分别从交通组织、桥梁结构和受力、施工、经济性等几个方面进行多方案比较分析,最终选择平层轨道居中的设计模式,其具有平纵线... 详细信息

以泉州金屿大桥为研究实例,根据公路和轨道所处位置及作用,提出平层、双层和分离3大形式,6种共建设计模式。分别从交通组织、桥梁结构和受力、施工、经济性等几个方面进行多方案比较分析,最终选择平层轨道居中的设计模式,其具有平纵线型协调、交通组织顺畅、设计简洁、施工方便、经济性好等优点。

关键词：泉州金屿大桥公轨共线组合模式多方案比选

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特大断面隧道原位扩建中的扩挖方案比选研究

路基工程 2017年第5期 183-187页

作者：林嗣雄福州市规划设计研究院福州350108

以金鸡山特大断面隧道原位扩建工程为背景,分别对传统中隔壁法扩挖方案和核心五步法扩挖方案进行精细化数值模拟,重点关注围岩压力、支护弯矩和洞身收敛随施工过程的动态变化。从施工效率上看,核心五步法扩挖方案由于简化了开挖分区,其... 详细信息

以金鸡山特大断面隧道原位扩建工程为背景,分别对传统中隔壁法扩挖方案和核心五步法扩挖方案进行精细化数值模拟,重点关注围岩压力、支护弯矩和洞身收敛随施工过程的动态变化。从施工效率上看,核心五步法扩挖方案由于简化了开挖分区,其施工步由传统中隔壁法的144步减少到124步。从围岩压力和初支弯矩上看,核心五步法扩挖方案中围岩压力的偏压状况得到明显缓解,初支弯矩分布更加均匀,且正负弯矩绝对值较小。从洞身收敛上看,两种扩挖方案相差不大。建议金鸡山隧道原位扩建工程采用核心五步法扩挖方案,能加快施工进度、减小围岩扰动、提高施工安全性。

关键词：特大断面隧道原位扩建扩挖方案传统中隔壁法核心五步法

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福州市金鸡山隧道衬砌水害调查与原因分析

福建建筑 2016年第4期 106-108页

作者：林嗣雄福州市规划设计研究院福建福州350108

隧道作为一种常见的地下结构形式,受地质条件、设计施工和运营环境的影响,在其服役寿命中后期常出现不同程度的病害,从而影响隧道内行车舒适性和安全性。本文以福州市二环路金鸡山隧道衬砌结构病害检测为背景,对其衬砌表面的水害呈现形... 详细信息

隧道作为一种常见的地下结构形式,受地质条件、设计施工和运营环境的影响,在其服役寿命中后期常出现不同程度的病害,从而影响隧道内行车舒适性和安全性。本文以福州市二环路金鸡山隧道衬砌结构病害检测为背景,对其衬砌表面的水害呈现形式、水害发生部位和最大出水量进行了详细的调查统计,分析了衬砌表面水害产生的原因,并对类似工程的水害防治提出建议。

关键词：山岭隧道衬砌结构水害调查水害防治

广播电视“智慧运维”人员评估模型的构建研究

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广播与电视技术 2020年第9期47卷 18-21页

作者：林嗣雄上海广播电视台技术中心上海200072

人员管理是广电“智慧运维”的四大要素之一,是整个组织的人力资源管理的一部分。本文从运维管理的角度出发,结合管理学的观点,提出了适用于广电“智慧运维”的人员评估方式和模型,在此基础上提出了一种运维人员评估的模式,并在上海广... 详细信息

人员管理是广电“智慧运维”的四大要素之一,是整个组织的人力资源管理的一部分。本文从运维管理的角度出发,结合管理学的观点,提出了适用于广电“智慧运维”的人员评估方式和模型,在此基础上提出了一种运维人员评估的模式,并在上海广播电视台技术中心进行了相关研究和探索。

关键词：人员评估智慧运维运维管理模型

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正骨活络油联合推拿治疗颈椎病的效果

中国实用乡村医生杂志 2024年第9期31卷 12-15页

作者：吴宇航林思雄陈智广福建中医药大学附属泉州中医院针灸科福建泉州362000 泉州市正骨医院微针科福建中医药大学附属泉州中医院针灸康复科

目的探讨正骨活络油联合推拿治疗颈椎病的效果。方法选取2021年1月—2023年6月在福建中医药大学附属泉州中医院接受正骨活络油联合推拿治疗的63例颈椎病患者作为联合治疗组,选取同期接受单纯推拿治疗的27例颈椎病患者作为推拿组。比较... 详细信息

目的探讨正骨活络油联合推拿治疗颈椎病的效果。方法选取2021年1月—2023年6月在福建中医药大学附属泉州中医院接受正骨活络油联合推拿治疗的63例颈椎病患者作为联合治疗组,选取同期接受单纯推拿治疗的27例颈椎病患者作为推拿组。比较两组患者治疗前后中医症候积分、疼痛情况、颈椎功能障碍情况及生活质量。结果治疗后两组患者中医症候积分、疼痛视觉模拟评分法评分、颈椎功能障碍指数评分、生活质量评分均较治疗前得到改善,且治疗后联合治疗组上述指标评分均优于推拿组,差异有统计学意义(P<0.05)。结论正骨活络油联合推拿治疗颈椎病,可进一步提高疗效,改善患者生活质量,值得临床推广使用。

关键词：颈椎病中医治疗推拿正骨活络油效果生活质量

泉州正骨托头手法治疗颈椎小关节紊乱症的临床观察

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中国中医骨伤科杂志 2024年第9期32卷 17-20页

作者：陈长贤林思雄杨原芳王金鑫林雅婷涂银勇徐杰泉州市正骨医院福建泉州362000

目的:观察泉州正骨托头手法治疗颈椎小关节紊乱症的临床疗效。方法:选取颈椎小关节紊乱症患者80例,随机分为观察组和对照组(各40例)。对照组予常规推拿治疗,观察组予泉州正骨托头手法治疗。以视觉模拟量表(VAS)评分、健康调查简表(SF-36... 详细信息

目的:观察泉州正骨托头手法治疗颈椎小关节紊乱症的临床疗效。方法:选取颈椎小关节紊乱症患者80例,随机分为观察组和对照组(各40例)。对照组予常规推拿治疗,观察组予泉州正骨托头手法治疗。以视觉模拟量表(VAS)评分、健康调查简表(SF-36)评分及临床疗效作为结局指标。结果:治疗后两组患者VAS评分均降低,差异有统计学意义(P<0.05),SF-36评分均升高,且观察组优于对照组,差异有统计学意义(P<0.05);治疗后观察组有效率高于对照组,差异有统计学意义(P<0.05)。结论:泉州正骨托头手法治疗颈椎小关节紊乱症,可缓解疼痛,改善生活质量,提高临床疗效。

关键词：泉州正骨托头手法颈椎小关节紊乱症常规推拿按摩