研究领域
招生信息
教育背景
工作经历
教授课程
专利与奖励
出版信息
科研活动
基本信息
陈棣男中国科学院深圳先进技术研究院
电子邮件： di.chen@siat.ac.cn
通信地址： 广东省深圳市南山区西丽大学城学苑大道1068号
邮政编码： 518055
研究领域
陈棣教授的专业领域为分子生物学，生物化学和骨生物学。陈棣教授多年来一直致力于骨关节疾病的发病机制和治疗方面的研究。研究方向主要为以转基因小鼠为模型构建的骨关节炎、強直性脊柱炎、风湿性关节炎以及遗传性骨病等，并探讨Wnt/β-catenin等相关信号通路在其发生发展中的作用。在此研究基础上，开发治疗骨关节相关疾病的新药，并探讨其临床转化效益。
1.One of my early research works was focused on BMP signaling and osteoblast differentiation. We cloned Bmp2, Bmp3and Bmp4genomic DNAs and cDNAs from different species and investigated function of BMP receptors and BMP signaling molecules Smad1/5. We have determined the role of BMP receptor in osteoblast differentiation and postnatal bone formation. Later we also determined the role of Bmp2and Bmp4 genes in skeletal development.
2. Runx2 in post-transcriptional regulation. My lab, for the first time identified specific Hect domain E3 ligases, Smurf1 and Smurf2, which recognized the PY motif of Runx2 and mediated Runx2 ubiquitination and proteasome degradation. We also found that Smad6 interacted with Runx2 and enhanced Smurf1-mediated Runx2 degradation. We also found that TNFα promotes Runx2 degradation via inducing Smurf up-regulation in osteoblasts.
3. We have investigated the role of PTH/PTHrP in chondrocyte function and OA development. My lab demonstrated, for the first time, that cell cycle protein cyclin D1/CDK4 induce Runx2 phosphorylation and subsequent ubiquitination/proteasome degradation. We found that PTHrP prevents chondrocyte premature hypertrophy through inducing cyclin D1-dependent Runx2 and Runx3 degradation. We also found that PTH has chondro-protective effect in an experimentally-induced OA mouse model.
4. I have made significant contributions in our understanding of chondrocyte β-catenin signaling in the development of arthritis, especially spondyloarthritis (SpA). We found that β-catenin expression was upregulated in patients with OA and disc degeneration. We generated a mouse model with chondrocyte-specific β-catenin conditional activation, β-catenin(ex3)Col2ER, showing defects in spine, including disc and facet joint, knee joint and temporomandibularjoint (TMJ). This mouse model closely resembles SpA phenotype.
5. We found that TGF-β signaling plays a critical role in OA development. Deletion of TGF-β type II receptor gene (Tgfbr2Col2ER) in a conditional KO mice caused time-dependent progression of OA-like phenotype. MMP13 and Adamts5 are key downstream target genes of TGF-β signaling in articular chondrocytes.
6. We have generated a chondrocyte-specific Col2-CreERtransgenic mouse model which can be used to delete floxed genes of interest in growth plate and articular chondrocytes and chondrocytes located in other tissues other than long bone. These transgenic mice have been demonstrated a very useful tool for mouse genetic studies. More than 20 papers have been published showing these mice could be used to mediate targeted gene deletion in chondrocytes.
7. Axin1 and Axin2 are key negative regulators of β-catenin signaling. Deletion of Axin2 has a high bone mass phenotype. We have generated Axin1 conditional allele and will determine the role of Axin1/Axin2 in skeletal pattern formation and in the development of genetic bone diseases.
8. We have investigated the role of miRNAs regulation in Runx2 expression and found that miR-204/miR-211 play a key role in regulation of Runx2 expression in mesenchymal progenitor cells. Currently we are generated MSC-specific miR-204/-211 double KO mice and determine the role of these miRNAs in OA development.
招生信息
招收博士生和硕士生。
招生专业
071010-生物化学与分子生物学083100-生物医学工程招生方向
骨与关节疾病损伤的机制和修复强直性脊柱炎的损伤机制和修复教育背景
1987-09--1992-12美国路易斯维尔大学医学院博士1977-09--1982-07天津医科大学医学院医学学士学位工作经历
工作简历
2011-07~2019-09,美国拉什大学,The John W. and Helen Watzek 终身教授2010-08~2011-07,美国罗切斯特大学医学院,Dean's 终身教授2008-08~2011-08,美国罗切斯特大学医学院,终身教授2006-08~2008-08,美国罗切斯特大学医学院,副教授（终身制）2003-08~2006-08,美国罗切斯特大学医学院,助理教授（终身制）2000-08~2003-08,美国德克萨斯大学圣安东尼奥健康科学中心,助理教授（研究型）1998-08~2000-08,德克萨斯州圣安东尼奥OsteoScreen公司,高级科学家1995-08~1998-08,德克萨斯州圣安东尼奥OsteoScreen公司,研究科学家1992-12~1995-07,美国路易斯维尔大学医学院,博士后1986-09~1987-08,美国路易斯维尔大学医学院,研究员1982-09~1986-07,天津医科大学医学院,讲师社会兼职
2015-01-01-今,成员：F1000Prime, Rheumatology and Clinical Immunology/Cartilage Disorders and Osteoarthritis section,2014-12-31-今,编委：Oncology and Translational Medicine,
2014-01-01-今,编委：Scientific Reports (Nature Publishing Group),
2013-01-01-今,主编：Journal of Orthopaedic Translation,
2012-01-01-今,编委：Bone Research,
2012-01-01-今,编委会成员：Osteoarthritis and Cartilage,
2011-01-01-今,副编委：American Journal of Stem Cells,
2009-01-01-今,编委会成员：Arthritis Research & Therapy,
2009-01-01-今,编委：Chinese Journal of Osteoporosis and Bone Mineral Research,
2008-01-01-今,编委：Journal of Cellular Biochemistry,
2006-01-01-今,编委会成员：Calcified Tissue International,
2005-01-01-今,编委：Journal of Orthopaedic Surgery and Research,
教授课程
Special topics course in ImmunologyOsteoblast BiologyMolecular Basis of DiseaseGenetic Diseases of the Musculoskeletal SystemOsteoblast Biology, Skeletal Development专利与奖励
奖励信息
（1） 国家科学技术进步奖, 二等奖, 国家级, 2015（2） 上海市科技进步奖, 一等奖, 市地级, 2014（3） 科学技术进步奖, 一等奖, 部委级, 2014（4） 中华医学科技奖, 二等奖, 其他, 2014（5） 上海医学科技奖, 二等奖, 其他, 2012专利成果
（ 1 ） Methods and devices for treating intervertebral disc disease, 实用新型, 2013, 第 3 作者, 专利号: US 2013/** A1（ 2 ） Animal model for osteoarthritis and intervertebral disc disease, 实用新型, 2011, 第 1 作者, 专利号: US 2011/** A1（ 3 ） Identification of compounds which stimulate bone formation using a cell-based screening assay targeing BMP signaling, 实用新型, 2004, 第 2 作者, 专利号: US 2004/** A1（ 4 ） Identification of specific modulators of bone formation, 实用新型, 2003, 第 3 作者, 专利号: US 2003/** A1（ 5 ） Methods and compositions for stimulating bone growth using inhibitors of microtubule assembly, 实用新型, 2003, 第 2 作者, 专利号: US 2003/** A1出版信息
发表论文
（1）Metformin limits osteoarthritis development and progression through activation of AMPK signalling,Annals of the Rheumatic Diseases,2020,通讯作者（2）Acute synovitis after trauma precedes and is associated with osteoarthritis onset and progression,Int J Mol Sci,2020,通讯作者（3）CHIP regulates skeletal development and postnatal bone growth,J Cell Physiol,2020,通讯作者（4）Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation,Bone Res,2020,通讯作者（5）Runx2 plays a central role in osteoarthritis development,J Orthop Transl,2020,通讯作者（6）Exploration of CRISPR/ Cas9-based gene editing as therapy for osteoarthritis,Annals of the Rheumatic Diseases,2019,通讯作者（7）The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression,Nature Communications,2019,通讯作者（8）Deletion of Axin1 in condylar chondrocytes leads to osteoarthritis-like phenotype in temporomandibular joint via activation of β-catenin and FGF signaling,J Cell Physiol,2019,通讯作者（9）Deletion of Runx2 in condylar chondrocytes disrupts TMJ tissue homeostasis.,J Cell Physiol,2019,通讯作者（10）Runx2 is required for postnatal intervertebral disc tissue growth and development,J Cell Physiol,2019,通讯作者（11）Growth factor signaling in osteoarthritis,Growth Factors,2019,通讯作者（12）Wnt signaling in bone, kidney, intestine, and adipose tissue and inter-organ interaction in aging.,Ann NY Acad Sci,2019,通讯作者（13）E3 ubiquitin ligase CHIP in normal cell function and in disease conditions.,Ann NY Acad Sci,2019,通讯作者（14）Serum miRNAs are potential biomarkers for detection of disc degeneration, among which miR-26a-5p suppresses Smad1 to regulate disc homeostasis,J Cell Mol Med,2019,通讯作者（15）Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint (TMJ) causes osteoarthritis-like defects,Int J Oral Sci,2018,通讯作者（16）CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells.,Bone Res,2018,通讯作者（17）Deletion of Runx2 in articular chondrocytes decelerates the progression of DMM-induced osteoarthritis in adult mice,Sci Rep,2017,通讯作者（18）Specific deletion of β-catenin in Col2-expressing cells leads to defects in epiphyseal bone,Int J Biol Sci,2017,通讯作者（19）Osteoarthritis: Toward a comprehensive understanding of pathological mechanism,Bone Res,2017,通讯作者（20）Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis,Curr Rheumatol Rep,2017,通讯作者（21）Post-axial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology,Ann NY Acad Sci,2017,通讯作者（22）The Rock inhibitor immortalizes rat nucleus pulposus and annulus fibrosus cells: Establishment of intervertebral disc cell lines with novel approaches.,Spine,2016,通讯作者（23）Sox9 directly regulates CTGF/CCN2 transcription in growth plate chondrocytes and in nucleus pulposus cells of intervertebral disc,Sci Rep,2016,通讯作者（24）Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis,Ann NY Acad Sci,2016,通讯作者（25）Runx2 and microRNAs regulation in bone and cartilage diseases,Ann NY Acad Sci,2016,通讯作者（26）Differential roles of TGF-β signaling in joint tissues during osteoarthritis development,Annals of the Rheumatic Diseases,2016,通讯作者发表著作
（1）Developmental and Evolutionary Perspectives on TMJ Tissue Engineering,Quintessence Publishing Co, Inc,2012-01,第4作者（2）Biochemical Mediators involved in Cartilage Degradation and the Induction of Pain in Osteoarthritis,InTech - Open Access Publisher,2012-01,第3作者（3）Genetic mouse models for osteoarthritis research,InTech - Open Access Publisher,2012-01,第5作者（4）Establishment and Evaluation of Animal Models of Disc Degeneration.,People’s Medical Publishing House,2013-01,第3作者（5）Molecular and Cell Biology in Orthopsedics,American Academy of Orthopaedic Surgeons,2013-01,第5作者（6）BMPs and Wnts in Bone and Cartilage Regeneration. In: A Tissue Regeneration Approach to Bone Repair,Springer International Publishing,2015-01,第1作者科研活动
科研项目
（ 1 ） miR-204/-211通过下调Runx2抑 制滑膜增生调控骨关节炎发生发展的作用机制研究, 参与,国家级,2019-01--2022-12参与会议
（1）Recent Progress in Arthritis Research 中华医学会第二十一届骨科学术会议暨第十四届COA学术大会2019-11-16（2）CRISPR/Cas9-mediated ablation of osteoarthritis-associated genes attenuates osteoarthritis progressionASBMR2019-09-22（3）Fibular hemimelia:The most common birth defect in lower limb粤港澳基础研究高峰论坛暨2019年广东省医师协会骨科分会基础学组年会2019-09-15（4）Bone and Cartilage Related中华医学会第二十一届骨科学术会议暨第十四届COA学术大会2018-11-20（5）Bone and Cartilage Related武汉联合国际骨科峰会2018-10-25（6）Bone and Cartilage RelatedICOBR (International Conference on Osteoporosis and Bone Research) 2018-10-17（7）Bone and Cartilage RelatedNY Symposium2018-10-10（8）Bone and Cartilage RelatedASBMR2018-09-282013 © 中国科学院大学，网络信息中心.
