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Microenvironmental stiffness mediates cytoskeleton re-organization in chondrocytes through laminin-FAK mechanotransduction

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International Journal of Oral Science 2022年第2期14卷 182-191页

作者： Chenchen Zhou Mengmeng Duan Daimo Guo Xinmei Du Demao Zhang Jing Xie State Key Laboratory of Oral Diseases&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina Department of Cariology and Endodontics West China Hospital of StomatologySichuan UniversityChengduChina

Microenvironmental biophysical factors play a fundamental role in controlling cell behaviors including cell morphology,proliferation,adhesion and differentiation,and even determining the cell fate.Cells are able to actively sense the surrounding mechanical microenvironment and change their cellular morphology to adapt to it.Although cell morphological changes have been considered to be the first and most important step in the interaction between cells and their mechanical microenvironment,their regulatory network is not completely clear.In the current study,we generated silicon-based elastomer polydimethylsiloxane(PDMS)substrates with stiff(15:1,PDMS elastomer vs.curing agent)and soft(45:1)stiffnesses,which showed the Young’s moduli of~450 k Pa and 46 kPa,respectively,and elucidated a new path in cytoskeleton re-organization in chondrocytes in response to changed substrate stiffnesses by characterizing the axis shift from the secreted extracellular protein lamininβ1,focal adhesion complex protein FAK to microfilament bundling.We first showed the cellular cytoskeleton changes in chondrocytes by characterizing the cell spreading area and cellular synapses.We then found the changes of secreted extracellular linkage protein,lamininβ1,and focal adhesion complex protein,FAK,in chondrocytes in response to different substrate stiffnesses.These two proteins were shown to be directly interacted by Co-IP and colocalization.We next showed that impact of FAK on the cytoskeleton organization by showing the changes of microfilament bundles and found the potential intermediate regulators.Taking together,this modulation axis of lamininβ1-FAK-microfilament could enlarge our understanding about the interdependence among mechanosensing,mechanotransduction,and cytoskeleton re-organization.

关键词： laminin mec stiffness

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Runxl protects against the pathological progression of osteoarthritis

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Bone Research 2021年第4期9卷 618-629页

作者： Chenchen Zhou Yujia Cui Yueyi Yang Daimo Guo Demao Zhang Yi Fan Xiaobing Li Jing Zou Jing Xie State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengduChina National Clinical Research Center for Oral Diseases Sichuan UniversityChengduChina Department of Pediatric Dentistry West China Hospital of StomatologySichuan UniversityChengduChina

Runt-related transcription factor-1(Runxl)is required for chondrocyte-to-osteoblast lineage commitment by enhancing both chondrogenesis and osteogenesis during vertebrate development.However,the potential role of Runxl in joint diseases is not well known.In the current study,we aimed to explore the role of Runxl in osteoarthritis induced by anterior cruciate ligament transaction(ACLT)surgery.We showed that chondrocyte-specific Runxl knockout(Runx1f/fCol2a1-Cre)aggravated cartilage destruction by accelerating the loss of proteoglycan and collagen II in early osteoarthritis.Moreover,we observed thinning and ossification of the growth plate,a decrease in chondrocyte proliferative capacity and the loss of bone matrix around the growth plate in late osteoarthritis.We overexpressed Runxl by adeno-associated virus(AAV)in articular cartilage and identified its protective effect by slowing the destruction of osteoarthritis in cartilage in early osteoarthritis and alleviating the pathological progression of growth plate cartilage in late osteoarthritis.ChIP-seq analysis identified new targets that interacted with Runxl in cartilage pathology,and we confirmed the direct interactions of these factors with Runxl by ChIP-qPCR.This study helps us to understand the function of Runxl in osteoarthritis and provides new clues for targeted osteoarthritis therapy.

关键词： osteoarthritis protective diseases

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Disturbed bone remodelling activity varies in different stages of experimental, gradually progressive apical periodontitis in rats

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International Journal of Oral Science 2019年第4期11卷 289-299页

作者： Ruoshi Xu Daimo Guo Xuedong Zhou Jianxun Sun Yachuan Zhou Yi Fan Xin Zhou Mian Wan Wei Du Liwei Zheng State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Cariology and EndodontologyWest China Hospital of StomatologySichuan UniversityChengduChina State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of PediatricsWest China Hospital of StomatologySichuan UniversityChengduChina

Bone remodelling keeps going through the lifespan of human by bone formation and bone resorption.In the craniofacial region,mandibles act as the main force for biting and chewing,and also become susceptible to a common bone-loss disease,namely,apical periodontitis,once infected dental pulp is not treated timely,during which bone resorption occurs from the apical foramen to the apical bone area.Although conventional root canal treatment(RCT)can remove the most of the infection,chronical apical periodontitis due to incomplete removal of dental pulp and subsequent microleakage will become refractory and more challenging,and this process has scarcely been specifically studied as a bone remodelling issue in rat models.Therefore,to study chronical and refractory apical periodontitis owing to incomplete cleaning of infected dental pulp and microleackage in vivo,we establish a modified rat model of gradually progressive apical periodontitis by sealing residual necrotic dental pulp and introducing limited saliva,which simulates gradually progressive apical periodontitis,as observed in the clinical treatment of chronical and refractory apical periodontitis.We show that bone-loss is inevitable and progressive in this case of apical periodontitis,which confirms again that complete and sound root canal treatment is crucial to halt the progression of chronical and refractory apical periodontitis and promote bone formation.Interestingly,bone remodelling was enhanced at the initial stage of apical periodontitis in this model while reduced with a high osteoblast number afterwards,as shown by the time course study of the modified model.Suggesting that the pathological apical microenvironment reserve its hard tissue formation ability to some degree but in a disturbed manner.Hopefully,our findings can provide insights for future bone regenerative treatment for apical periodontitisassociated bone loss.

关键词： incomplete modelling progressive

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财政的本质属性与内在要求

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财政科学 2020年第9期 68-74页

作者：郭代模李栋不详中国财政科学研究院研究生院

对财政本质的准确认识,是做好财政研究工作的重要前提。本文在梳理财政理论发展的历史脉络基础上,阐述了财政本质的内在要求,并对准确认识财政本质需要把握的几个要点进行了论述,即透过现象看本质、克服片面看本质、坚持中国特色看本质... 详细信息

对财政本质的准确认识,是做好财政研究工作的重要前提。本文在梳理财政理论发展的历史脉络基础上,阐述了财政本质的内在要求,并对准确认识财政本质需要把握的几个要点进行了论述,即透过现象看本质、克服片面看本质、坚持中国特色看本质、坚持时代主题看本质。

关键词：财政本质内在要求

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口腔肿瘤患者精神心理因素评估及相关物质基础的初步研究

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华西口腔医学杂志 2014年第1期32卷 45-50页

作者：李博李黎段泽西黄一冰潘唯一郭黛墨邹晓莉朱彩蓉谢蟪旭口腔疾病研究国家重点实验室华西口腔医院头颈肿瘤外科(四川大学) 四川大学华西第二医院病案管理科四川大学华西公共卫生学院卫生检验学教研室卫生统计教研室成都610041

目的认识口腔肿瘤患者及配偶的精神心理因素变化规律,探索其相关物质基础。方法选取2011年12月—2012年8月间四川大学华西口腔医院确诊的口腔恶性肿瘤患者40例、良性肿瘤患者35例、恶性肿瘤配偶18例,应用症状自评量表(SCL90)按照5级评... 详细信息

目的认识口腔肿瘤患者及配偶的精神心理因素变化规律,探索其相关物质基础。方法选取2011年12月—2012年8月间四川大学华西口腔医院确诊的口腔恶性肿瘤患者40例、良性肿瘤患者35例、恶性肿瘤配偶18例,应用症状自评量表(SCL90)按照5级评分标准,测评每位受试者精神心理状况。于入院次日上午9点抽取受试者的全血,分离提取血清,采用高效液相色谱-质谱分析血清中儿茶酚胺以及糖皮质激素含量。结果恶性肿瘤组强迫症状、抑郁与其他因子分均高于良性肿瘤组,差异有统计学意义(P<0.05);恶性肿瘤组强迫症状、偏执与恐怖因子分均高于恶性肿瘤配偶组,差异有统计学意义(P<0.05)。各组间总分及其他单项因子分差异无统计学意义。血清中肾上腺素、去甲肾上腺素、氢化可的松及可的松的检测中,恶性肿瘤组与良性肿瘤组、恶性肿瘤配偶组间差异均有统计学意义(P<0.001)。结论口腔肿瘤患者存在明显的精神心理因素变化,同时伴有机体内相关物质变化,影响着恶性肿瘤的发生发展,对进一步研究恶性肿瘤疾病进程的相关机制及探索干预方法有重要价值。

关键词：症状自评量表口腔肿瘤高效液相色谱-质谱

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