基本信息

陈棣  男    中国科学院深圳先进技术研究院

国家杰出人才
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, Bmp3 and Bmp4 genomic 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 Bmp2 and 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 temporomandibular joint (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-CreER transgenic 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
100706-药理学
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 Immunology
Osteoblast Biology
Molecular Basis of Disease
Genetic Diseases of the Musculoskeletal System
Osteoblast 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 2013/0297023 A1
( 2 ) Animal model for osteoarthritis and intervertebral disc disease, 实用新型, 2011, 第 1 作者, 专利号: US 2011/0289605 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 2004/0009511 A1
( 4 ) Identification of specific modulators of bone formation, 实用新型, 2003, 第 3 作者, 专利号: US 2003/0092603 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 2003/0181374 A1

出版信息

   
发表论文
(1) AMPK Signaling in Energy Control, Cartilage Biology, and Osteoarthritis, Frontiers in Cell and Developmental Biology, 2021, 通讯作者
(2) Metformin limits osteoarthritis development and progression through activation of AMPK signalling, Annals of the Rheumatic Diseases, 2020, 通讯作者
(3) Acute synovitis after trauma precedes and is associated with osteoarthritis onset and progression, Int J Mol Sci, 2020, 通讯作者
(4) CHIP regulates skeletal development and postnatal bone growth, J Cell Physiol, 2020, 通讯作者
(5) 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
(6) Runx2 plays a central role in osteoarthritis development, J Orthop Transl, 2020, 通讯作者
(7) Exploration of CRISPR/ Cas9-based gene editing as therapy for osteoarthritis, Annals of the Rheumatic Diseases, 2019, 通讯作者
(8) The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression, Nature Communications, 2019, 通讯作者
(9) 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
(10) Deletion of Runx2 in condylar chondrocytes disrupts TMJ tissue homeostasis., J Cell Physiol, 2019, 通讯作者
(11) Runx2 is required for postnatal intervertebral disc tissue growth and development, J Cell Physiol, 2019, 通讯作者
(12) Growth factor signaling in osteoarthritis, Growth Factors, 2019, 通讯作者
(13) Wnt signaling in bone, kidney, intestine, and adipose tissue and inter-organ interaction in aging., Ann NY Acad Sci, 2019, 通讯作者
(14) E3 ubiquitin ligase CHIP in normal cell function and in disease conditions., Ann NY Acad Sci, 2019, 通讯作者
(15) 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
(16) 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
(17) CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells., Bone Res, 2018, 通讯作者
(18) Deletion of Runx2 in articular chondrocytes decelerates the progression of DMM-induced osteoarthritis in adult mice, Sci Rep, 2017, 通讯作者
(19) Specific deletion of β-catenin in Col2-expressing cells leads to defects in epiphyseal bone, Int J Biol Sci, 2017, 通讯作者
(20) Osteoarthritis: Toward a comprehensive understanding of pathological mechanism, Bone Res, 2017, 通讯作者
(21) Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis, Curr Rheumatol Rep, 2017, 通讯作者
(22) Post-axial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology, Ann NY Acad Sci, 2017, 通讯作者
(23) 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
(24) 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
(25) Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis, Ann NY Acad Sci, 2016, 通讯作者
(26) Runx2 and microRNAs regulation in bone and cartilage diseases, Ann NY Acad Sci, 2016, 通讯作者
(27) 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
( 2 ) 基于骨关节炎分子调控机制研究制定创新的治疗骨关节炎的新方法, 主持, 国家级, 2021-01--2025-12
参与会议
(1)脊柱脊髓科学问题的凝练与转化   第十四届上海国际骨科前沿技术与临床转化学术会议   2021-06-12
(2)强直性脊柱炎研究进展   第二届红会儿童骨骼畸形与损伤疾病高峰论坛   2021-06-04
(3)评审   2021年(上半年)医学科学领域原创探索计划项目(专家推荐类)评审会   2021-05-25
(4)强直性脊柱炎研究进展   老年骨关节病发病机理与早期干预学术讨论会——香山科学会议学术讨论会   2021-05-15
(5)骨关节研究进展   中华医学会手外科学分会第十二届华东地区学术会议暨创面修复重建研讨会   2021-04-15
(6)强直性脊柱炎研究进展   科技部十四五重点研发计划功能材料专项申报研讨会   2021-04-11
(7)骨关节研究进展   重庆市医学会骨科专业委员会第十八次学术年会   2021-04-09
(8)骨关节研究进展   个性化精准化膝关节周围截骨手术培训   2021-03-24
(9)强直性脊柱炎研究进展   《青岛大学附属医院第一届骨科基础论坛》   2021-03-09
(10)骨关节研究进展   《2021青年骨科医师基础研究金陵论坛》   2021-03-05
(11)强直性脊柱炎研究进展   第五届骨生物学国际前沿研讨会   2021-01-05
(12)骨关节研究进展   《湖北省骨生物材料与组织工程专业委员会第六届年会》和《暨武汉市颈肩腰腿痛生物临床专业委员会成立大会》   2020-10-26
(13)骨关节研究进展   骨生物学基础研讨会   2020-09-28
(14)骨关节炎药物研发   2020年安济盛药物创新研讨会   2020-08-28
(15)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
(16)CRISPR/Cas9-mediated ablation of osteoarthritis-associated genes attenuates osteoarthritis progression   ASBMR   2019-09-22
(17)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
(18)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
(19)Bone and Cartilage Related   武汉联合国际骨科峰会   2018-10-25
(20)Bone and Cartilage Related   ICOBR (International Conference on Osteoporosis and Bone Research)    2018-10-17
(21)Bone and Cartilage Related   NY Symposium   2018-10-10
(22)Bone and Cartilage Related   ASBMR   2018-09-28