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SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity

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Bone Research 2018年第2期6卷 132-144页

作者： Chunlin Zuo Lijun Wang Raghavendra M.Kamalesh margot e.bowe. Douglas C.Moore Mark S.Dooner Anthony M.Reginato Qian Wu Christoph Schorl Yueming Song Matthew L.Warman Benjamin G.Neel Michael G.ehrlich Wentian Yang Department of Orthopaedics Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Orthopaedic Research Laboratories and Howard Hughes Medical Institute Boston Children's Hospital and Department of GeneticsHarvard Medical SchoolBostonMA 02115USA Division of Hematology and Oncology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Division of Rheumatology Brown University Alpert Medical School and Rhode Island HospitalProvidenceRI 02903USA Department of Pathology and Laboratory Medicine University of Connecticut Health CenterFarmingtonCT 06030USA Department of Molecular and Cell Biology and Biochemistry Brown University70 Ship StreetProvidenceRI 02912USA Department of Orthopedic Surgery West China Hospital of Sichuan UniversityChengdu 610041 Laura and Issac Perlmutter Cancer Center NYU Langone Medical CenterNew YourkNY 10016USA Department of endocrinology the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene ***2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.

关键词： SHP2 regulates skeletal cell modifying SOX9 expression transcriptional activity SOX

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10-14岁青少年，你在想什么

加拿大钢铁公司希尔顿厂冷轧机用化学品和油的管理技术的革新

作者： (英)Rebecca Bergese，(英)margot Waddell

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国外钢铁 1997年第10期22卷 54-60页

作者： bowe.,Re 许玲

通过对冷轧机用化学品，油和水的管理，希尔顿水厂进行了三项技术革新，碱洗液循环（超滤），液压油循环（热真空脱水）和工业用水代替饮用水（自动回洗过滤和超滤）使得生产成本降低并改善了产品质量。

关键词：冷轧机化学试剂油水管理成本钢铁企业

A pharmacologist's journey in medical education:a personal history

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Acta Pharmacologica Sinica 2004年第9期25卷 102-106页

作者： e e DANIeL AB T6G 2H7 Canada Department of Pharmacology Room 9-10 edmonton MSB University of Alberta

My journey as an educator in Pharmacology began in 1949, when, after finishing my MA in Biology at Johns Hopkins, Ⅰ decided that Ⅰ wanted to be involved in science with more relevance to humans. Ⅰhad been chasing f... 详细信息

关键词： ACe A pharmacologist’s journey in medical education

20世纪90年代美国工程专业学生和教师供给状况分析

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中外高教研究 1992年第4期7卷 103-111页

作者： bowe.,JR 沈跃进

Validation of CFD-DeM model for iron ore reduction at particle level and parametric study

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Particuology 2020年第4期18卷 163-172页

作者： Dianyu e International Research Institute for Minerals Metallurgy and MaterialsJiangxi University of Science and TechnologyNanchang 330013China Department of Chemical engineering Monash UniversityClaytonVIC 3800Australia

Iron ore reduction is a primary unit operation in current metallurgy processes and dominates the energy consumption and greenhouse gas(GHG)emissions of the iron-making process,Therefore,even a slight improvement of the energy efficiency or GHG emissions of iron ore reduction would yield considerable benefits to the cost of pig iron and,more importantly,to mitigation of the associated carbon *** current study presents a discrete model that describes the iron ore reduction process for a single *** transient reaction progress can be predicted and is validated against experimental measurements under various operating conditions,including different reducing gases and *** effects of pressure,isothermality,gas composition,and flow rate on reduction are *** reduction rate increases significantly with increasing pressure until 5 atm,and the entire reduction process occurs more slowly under non-isothermal conditions than under isothermal *** work provides a solid foundation for the development of a comprehensive particulate system model that considers both heat and mass transfer.

关键词： Iron ore reduction Chemical reaction Blast furnace Discrete element method Computational fluid dynamics

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等你十八年

跨世纪(时文博览) 2010年第2期 32-34页

作者： margot

他惊喜万分,在e-mail的结尾,他说:"艾琳,我对你的感情一如1985年我们第一次相见时一般热烈。我爱你,我想你,我仍然单身,我要去中国看你,你等我。"伊斯兰堡的甜蜜阳光下1985年的夏天,作为商务代表团的随团翻译,刚从外院毕业的我第一次踏... 详细信息

他惊喜万分,在e-mail的结尾,他说:"艾琳,我对你的感情一如1985年我们第一次相见时一般热烈。我爱你,我想你,我仍然单身,我要去中国看你,你等我。"伊斯兰堡的甜蜜阳光下1985年的夏天,作为商务代表团的随团翻译,刚从外院毕业的我第一次踏上了异国的土地,土耳其的安卡拉。尽管整整32个小时的飞行和转机将我折磨得筋疲力尽,可是刚踏进酒店的大门,我的目光就被一位英俊非凡的外国小伙子吸引住了。正当我向他凝

关键词：土耳其我爱你中华人民共和国婚姻生活电信电话看你艾琳单身想你丈夫幸福北京

HIV感染者487例所患皮肤疾病与免疫缺陷的关系

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中国皮肤性病学杂志 2007年第1期21卷 36-38页

作者：鲍迎秋傅裕常建民 margot Whitfeld 卫生部北京医院皮肤科北京100730 Skin and Cancer Foundation NSW 2010Australia

目的分析HIV感染者皮肤表现和HIV感染所致免疫缺陷程度的相关性;发现患有两个及多个皮肤疾病的危险因素。方法对悉尼某皮肤科诊所1995～2005年的487例HIV阳性患者的病历资料进行回顾性分析,应用统计学软件对不同皮肤疾病与相关CD4计数... 详细信息

目的分析HIV感染者皮肤表现和HIV感染所致免疫缺陷程度的相关性;发现患有两个及多个皮肤疾病的危险因素。方法对悉尼某皮肤科诊所1995～2005年的487例HIV阳性患者的病历资料进行回顾性分析,应用统计学软件对不同皮肤疾病与相关CD4计数的关系、患有两个及以上皮肤疾病的危险因素进行分析。结果487例患者中,485(99.6%)例有皮肤病的诊断,平均每例2.55个诊断。男性患者共479例。日光相关性皮肤病主要发生于CD4>400cells/μL的患者,很多感染性和炎症性皮肤病多发生于中度免疫抑制(250≤CD4≤450cells/μL),传染性软疣和嗜酸性毛囊炎见于CD4ells/μL的患者。CD4计数ells/μL和年龄≥40岁是发生2个以上皮肤病的危险因素。结论皮肤表现与HIV感染所致免疫缺陷程度密切相关。

关键词：皮肤疾病 HIV AIDS 免疫缺陷

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袁泉夏雨浇灌一场纯纯的爱

东西南北（大学生版） 2005年第11期 50-51页

作者： margot

也许我和袁泉只是百分之七十的恋人,可是我们能在一起去创造那剩下的百分之三十,爱情的美好就在于此。

关键词：夏雨袁泉刘烨买东西我自己学校操场图书管理员印象派画家七年之痒单板滑雪