Prof. Chen Di specializes in molecular biology, biochemistry and bone biology. Prof. Chen Di has been devoted to the research of pathogenesis and treatment of bone and joint diseases for many years. The main research interests are exploring role of Wnt/β-Catenin and other related signaling pathways in osteoarthritis, ankylosing spondylitis, rheumatoid arthritis and hereditary osteopathy via applying transgenic mice as mice models. Then focus on discovering new drugs for rescue and treatment of bone and joint related diseases for potential clinical applicaiton.

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 (Tgfbr2^Col2ER) 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.

1977-1982 M.D., Tianjin Medical University School of Medicine, Tianjin, China

1986-1987 Research Fellow, Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, Kentucky

1987-1992 Ph.D., Department of Pharmacology and Toxicology University of Louisville School of Medicine, Louisville, Kentucky

1992-1995 Post-doctoral Fellow, Department of Medicine, Division of Endocrinology, University of Texas Health Science Center at San Antonio, San Antonio, Texas

1982-1986 Instructor, Department of Pharmacology Tianjin Medical University, School of Medicine, Tianjin, China

1995-1998 Research Scientist

1998-2000 Senior Scientist OsteoScreen Inc., San Antonio, Texas

2000-2003 Assistant Professor (research-track) Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, Texas

2003-2006 Assistant Professor (tenure-track), Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York

2006-2008 Associate Professor (tenure-track),Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York

2008-2011 Professor with tenure, Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York

2010-2011 Dean’s Professor, Department of Orthopaedics and Rehabilitation, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, New York

 2011-2019 The John W. and Helen Watzek Professor, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, Illinois

Teaching Experience (University of Rochester)

1. Orthopaedic Basic Science Conferences (Orthopaedic residence course)         

Lecture: Genetic Diseases of the Musculoskeletal System (2006, 2007)

2. IND 593: Skeletal Biology and Pathology (Graduate student course)

Lecture: Osteoblast Biology, Skeletal Development (2006, 2007)

3. PTH 593: Molecular Basis of Disease (Graduate student course)

Course director: Di Chen (2007-2009)

Lecture: Genetic Skeletal Disorders

4. IND 593: Orthopaedic Basic Science (Graduate student course)

Lecture: Osteoblast Biology (2010)

Teaching Experience (Rush University)

Special topics course in Immunology (Graduate College, 2014)

（1） AMPK Signaling in Energy Control, Cartilage Biology, and Osteoarthritis, Frontiers in Cell and Developmental Biology, 2021, Corresponding author

（2）Metformin limits osteoarthritis development and progression through activation of AMPK signalling, Annals of the Rheumatic Diseases, 2020, Corresponding author

（3） Acute synovitis after trauma precedes and is associated with osteoarthritis onset and progression, Int J Mol Sci, 2020, Corresponding author
（4） CHIP regulates skeletal development and postnatal bone growth, J Cell Physiol, 2020, Corresponding author
（5） Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation, Bone Res, 2020, Corresponding author
（6） Runx2 plays a central role in osteoarthritis development, J Orthop Transl, 2020, Corresponding author
（7） Exploration of CRISPR/ Cas9-based gene editing as therapy for osteoarthritis, Annals of the Rheumatic Diseases, 2019, Corresponding author
（8） The microRNAs miR-204 and miR-211 maintain joint homeostasis and protect against osteoarthritis progression, Nature Communications, 2019, Corresponding author
（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, Corresponding author
（10） Deletion of Runx2 in condylar chondrocytes disrupts TMJ tissue homeostasis., J Cell Physiol, 2019, Corresponding author
（11） Runx2 is required for postnatal intervertebral disc tissue growth and development, J Cell Physiol, 2019, Corresponding author
（12） Growth factor signaling in osteoarthritis, Growth Factors, 2019, Corresponding author
（13） Wnt signaling in bone, kidney, intestine, and adipose tissue and inter-organ interaction in aging., Ann NY Acad Sci, 2019, Corresponding author
（14） E3 ubiquitin ligase CHIP in normal cell function and in disease conditions., Ann NY Acad Sci, 2019, Corresponding author
（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, Corresponding author
（16） Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint (TMJ) causes osteoarthritis-like defects, Int J Oral Sci, 2018, Corresponding author
（17） CHIP regulates bone mass by targeting multiple TRAF family members in bone marrow stromal cells., Bone Res, 2018, Corresponding author
（18） Deletion of Runx2 in articular chondrocytes decelerates the progression of DMM-induced osteoarthritis in adult mice, Sci Rep, 2017, Corresponding author
（19） Specific deletion of β-catenin in Col2-expressing cells leads to defects in epiphyseal bone, Int J Biol Sci, 2017, Corresponding author
（20） Osteoarthritis: Toward a comprehensive understanding of pathological mechanism, Bone Res, 2017, Corresponding author
（21） Wnt/β-catenin signaling in osteoarthritis and in other forms of arthritis, Curr Rheumatol Rep, 2017, Corresponding author
（22） Post-axial limb hypoplasia (PALH): the classification, clinical features, and related developmental biology, Ann NY Acad Sci, 2017, Corresponding author
（23） The Rock inhibitor immortalizes rat nucleus pulposus and annulus fibrosus cells: Establishment of intervertebral disc cell lines with novel approaches., Spine, 2016, Corresponding author
（24） Sox9 directly regulates CTGF/CCN2 transcription in growth plate chondrocytes and in nucleus pulposus cells of intervertebral disc, Sci Rep, 2016, Corresponding author
（25） Wnt/β-catenin signaling plays a key role in the development of spondyloarthritis, Ann NY Acad Sci, 2016, Corresponding author
（26） Runx2 and microRNAs regulation in bone and cartilage diseases, Ann NY Acad Sci, 2016, Corresponding author
（27） Differential roles of TGF-β signaling in joint tissues during osteoarthritis development, Annals of the Rheumatic Diseases, 2016, Corresponding author

1. United States Patent Application Publication

Pub. No.: US 2003/0092603 A1

Pub. Date: May. 15, 2003

Title of invention: Identification of Specific Modulators of Bone Formation.

Inventors: Gregory R. Mundy, I. Ross Garrett, Di Chen, G. Rossini, M. Zhao

Country: United States

2. United States Patent Application Publication

Pub. No.: US 2003/0092603 A1

Pub. Date: Sept 25, 2003

Title of invention: Methods and Compositions for Stimulating Bone Growth Using Inhibitors of Microtubule Assembly.

Inventors: Gregory R. Mundy, Di Chen, Mei Qiao, Jorge Gianni Rossini, Ming Zhao

Country: United States

3. United States Patent Application Publication

Pub. No.: US 2004/0009511 A1

Pub. Date: Jan. 15, 2004

Title of invention: Identification of Compounds which Stimulate Bone Formation Using A Cell-Based Screening Assay Targeting BMP Signaling.

Inventors: Gregory R. Mundy, Di Chen, Ming Zhao

Country: United States

4. United States Patent Application Publication

Pub. No.: US 2011/0289605 A1

Pub. Date: Nov. 24, 2011

Title of invention: Animal Model for Osteoarthritis and Intervertebral Disc Disease

Inventors: Di Chen

Country: United States

5. United States Patent Application Publication

Pub. No.: US 2013/0297023 A1

Pub. Date: Nov. 3, 2013

Title of Invention: Methods and Devices for Treating Intervertebral Disc Disease

Inventors: Hee-Jeong Im Sampen, Howard S. An, Di Chen

Country: United States

US Patents (Filed):

6. U.S. Provisional Application No.: 61/799,888

U.S. Application Serial No. 61/799,888

U.S. File No. 14904-12

Title of invention: Methods for Treating Cancer.

Inventor: Di Chen

Title: Composition and Methods for Treating Cancer

Country: United States

Filed in 2014

7. United States Patent and Trademark Office

Provisional Application for United States Letters Patent

Attorney Case No. 14904/104
Client Reference No. R468

Title of invention: Compositions and Methods for Treating Bone Diseases.

Inventors: Di Chen, Rong Xie

Country: United States

Flied in 2014

International Patents (Published):

8. International Application Published Under the Patent Cooperation Treaty (PCT)

Int. Pub. No.: WO 03/030924 A1

Int. Pub. Date: 17 April 2003

Title of invention: Identification of Specific Modulators of Bone Formation.

Inventors: Gregory R. Mundy, I. Ross Garrett, Di Chen

Country: WIPO

9. International Application Published Under the Patent Cooperation Treaty (PCT)

Int. Pub. No.: WO 03/059277 A2

Int. Pub. Date: 24 July 2003

Title of invention: Methods and Compositions for Stimulating Bone Growth Using Inhibitors of Microtubule Assembly.

Inventors: Di Chen, Jorge Gianni Rossini, Ming Zhao, Mei Qiao, Gregory R. Mundy

Country: WIPO

10. International Application Published Under the Patent Cooperation Treaty (PCT)

Applicant/Proprietor: University of Rochester (Inventor: Di Chen)

Application No/Patent No: 09829788.0-1223 PCT/US2009065911  

Date of Filing: November 25, 2009

Priority:

US/25.11.08/ USP 117766

US/06.08.09/ USP 231852

Title: Animal Model for Osteoarthritis and Intervertebral Disc Disease.

Country: WIPO

International Patents (Filed):

11. International Application Published Under the Patent Cooperation Treaty (PCT)

Applicant: Rush University Medical Center

International Application No.: PCT/US2014/025459

International Filing Date: 13 March 2014

Title of invention: Methods for Treating Cancer.

Inventors: Di Chen

Country: WIPO

（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

1. Fellowship (1986-1987), University of Louisville

2. Travel Award (2002), Ninth Workshop on Cell Biology of Bone and Cartilage in Health and Disease; March, 2002; Davos, Switzerland.

3. Outstanding Paper Award (2002), International Osteoporosis Conference, Shanghai, China.

4. Travel award (2003), Biennial Scientific Meeting of the International Bone and Mineral Society (IBMS); June, 2003; Osaka, Japan

5. Novartis Young Investigator Award (2005), Second Joint Meeting of the European Calcified Tissue Society (ECTS) and International Bone and Mineral Society (IBMS), June 25-29, 2005; Geneva, Switzerland

6. Independent Scientist Award (2006), NIH/NIAMS

7. Visiting Fellow, ANZAC Research Institute, University of Sydney, Oct-Nov, 2006

8. Best Paper Award (2008), International Conference on Osteoporosis and Bone Research (ICOBR); October 22-25, 2008; Beijing, China.

9. The post-doctoral fellows and graduate students in my lab won 9 ASBMR young investigator awards, 7 ORS new investigator recognition awards (NIRA), 3 ASBMR young investigator travel awards, 4 IBMS young investigator travel awards, 2 GRC travel awards, 11 ICMRS Web Jee young investigator awards, and 5 other awards (total 41 awards).