Bone & Cartilage Research

George R. Dodge, PhD
Laboratory Head

Overview:

Dr. Dodge’s studies focus upon the cells that produce cartilage and bone and the molecular pathways that are involved in repair and development. One area is the study of the large heparan sulfate proteoglycan, perlecan, and its expression and characteristics in cartilage and diseases involving cartilage and bone. An intriguing and recent finding of the laboratory is the identification of an alternatively spliced form of the gene resulting in a much smaller protein with perlecan-like and novel protein sequences. We are exploring this new proteins role in health and disease in areas such as normal cartilage and bone development and in diseases such as cancer and abnormal bone growth. The laboratory is active at engineering a cartilage replacement tissue that could effectively serve to replace damaged cartilage in the joint and in other cartilaginous tissues. Teamed with the University of Pennsylvania group of Dr. Reddy and using animal and ex vivo models, Dr. Dodge has studied the ability of magnetic resonance imaging and sodium imaging to identify small but significant degenerative changes in cartilage. This may be a method with the potential of detecting early changes in human joint disease and critically evaluating the effectiveness of therapy. As Director of the Orthopaedic Research Program, Dr. Dodge participates in and organizes orthopaedic research with other members of the Nemours community. Within his laboratory, Orthopaedic Research and Clinical Fellows participate in basic and applied research projects. This provides to Fellows opportunities for learning and will increase the productivity and visibility of orthopaedic research. Additionally during the past year, several physicians in Orthopaedics, Pediatrics, Surgery, and Critical Care have come into the laboratory and both performed preliminary studies and developed research proposals for obtaining intramural and extramural research grants. These projects include bone growth and obesity, lung injury and lung extracelluar matrix, and studies on the importance of the extracellular matrix in neuroblastomas. Projects with direct clinical relevance include one on epiphysiodesis with Dr. Bowen that focuses upon the use of electrical stimulation to affect an epiphysiodesis, a procedure commonly used for correcting abnormal bone growth. The potential outcome of this study could be the scientific basis for a new technique to perform this corrective procedure without surgery and avoid the associated costs, trauma, and complications. Continuing studies, including one on calmodulin and bracing, which is a multi-center Nemours project. Collectively, these studies are of particularly important to the Nemours community because of the many growth and orthopaedic disorders in children. More research is needed to understand the abnormalities and molecular causes for these disabling and perplexing disorders.

Research Interests:

• Cartilage extracellular matrix
• Chondrocyte cell biology
• Regulation of matrix gene expression in Arthritis

Selected Publications:

• Wheaton, A.J., G.R. Dodge, D.M. Elliot, S.B. Nicoll and R. Reddy (2005). Quantification of Cartilage and Biomechanical Properties via T1? magnetic resonance imaging. Magn. Reson. Med. 54:1087-1093.
• Wheaton, A.J., G.R. Dodge, A. Borthakur, J.B. Kneeland, H.R. Schumacher and R. Reddy (2004). Detection of changes in articular cartilage proteoglycan by T1? magnetic resonance imaging. J. Orthopaedic Res. 54:102-108.
• Wheaton, A.J., F.L. Casey, A.J. Gougoutas, G.R. Dodge, A. Borthakur, J.H. Lonner, H.R. Schumacher and R. Reddy (2004). Correlation of T1? with fixed charge density in cartilage. J. Magn. Reson. Imaging. 20:519-525.
• Wheaton, A.J., A. Borthakur, G.R. Dodge, J.B. Kneeland, H.R. Schumacher and R. Reddy (2004). Sodium magnetic resonance imaging of proteoglycan depletion in an in vivo model of osteoarthritis. Acad Radiol. 11:21-28.
• Dodge, G.R. and S.A. Jimenez (2003). Glucosamine sulfate modulates the levels of aggrecan and matrix metalloproteinase-3 synthesized by cultured adult human osteoarthritis articular chondrocytes. Osteoarthritis and Cartilage 11:424-432.
• Richardson, D.W. and G.R. Dodge (2003). Dose-dependant effects of corticosteriods on the expression of matrix related genes in normal and cytokine treated articular chondrocytes. Inflammation Res. 52:39-49.
• Tsark, E.C., W. Wang, Y-C. Teng, D. Arkfeld, G.R. Dodge and S. Kovats (2002). Differential MHC Class II-mediated Presentation of Rheumatoid Arthritis Autoantigens by Human Dendritic Cells and Macrophages. J. Clin. Invest. 66:25-33.
• Estrada, L.E., G.R. Dodge, D.W. Richardson, A. Farole and S.A. Jimenez (2001). Characterization of cartilage-like tissue produced in an in vitro model of chondrogenesis using porcine neonatal chondrocytes. Osteoarthritis Cartilage 9:169-177.
• Noyszewski, E.A., K. Wroblewski, G.R. Dodge, S. Kudchodkar, J. Beers, A.V.S. Sarma and R. Reddy (2001). Preferential Incorporation of Glucosamine into the Galactosamine Moieties of Chondroitin Sulfates in Articular Cartilage Explants. Arthritis and Rheum. 44:1089-1095.
• Richardson, D.W. and G.R. Dodge (2000). Effects of interleukin-1ß and tumor necrosis factor-a on the expression of matrix related genes in cultured equine articular chondrocytes. Am. J. of Vet. Res. 61:624-630.
• Fang, Q., Y-Y. Sun, W. Cai, G.R. Dodge, P. Lotke and W.V. Williams (1999). Cartilage-reactive T cells in rheumatoid synovium. Intl. Immunol. 12:659-669.
• Dodge, G.R., A. Diaz, C. Sanz-Rodriguez, A.M. Reginatio and S.A. Jimenez (1998). Effects of interferon-? and tumor necrosis factor a on the expression of the genes encoding aggrecan, biglycan, and decorin core proteins in cultured human chondrocytes. Arthritis and Rheum. 41:274-283.
• Dodge, G.R., D. Hawkins, E. Boesler, L. Sakai and S.A. Jimenez (1998). Cartilage oligomeric matrix protein (COMP) is produced by human dermal and synovial fibroblasts. Osteoarthritis and Cartilage 6:435-440.
• Richardson, D.W. and G.R. Dodge (1998). Molecular characteristics of equine stromelysin (MMP-3) and the tissue inhibitor of metalloproteinase-1 (TIMP-1). Am. J. of Vet. Res. 59:1557-62.
• Jordan, K.L., T.J. Logan, P. Norton, M. Stubbs, I-S., Min, A. Derfoul, G.R. Dodge and D.J. Hall (1997). Reduction in fibronectin expression and alteration in cell morphology are coincident in NIH3T3 cells expressing a mutant E2F-1 transcription factor. Exp. Cell Res. 236:527-536.
• Jimenez, S.A., L. Ala-Kokko, D.J. Prockop, C.F. Merryman, N. Shepard and G.R. Dodge (1997). Characterization of human type II procollagen and collagen-specific antibodies and there application to study human type II collagen processing and ultrastructure. Matrix Biol. 16:29-39.
• Richardson, D.W. and G.R. Dodge (1997). Cloning of Equine type II procollagen and the modulation of its expression in cultured equine chondrocytes. Matrix Biol. 16:59-65.
• Dodge, G.R., E.W. Boesler and S.A. Jimenez (1995). Expression of the basement membrane heparan sulfate proteoglycan (perlecan) in human synovium and in cultured synovial cells. Lab. Invest. 73:649-657.
• Murdoch, A.D., G.R. Dodge, I. Cohen, R.S. Tuan and R.V. Iozzo (1992). Primary structure of the human heparan sulfate proteoglycan from basement membrane (HSPG2/Perlecan). A chimeric molecule with multiple domains homologous to the low density lipoprotein receptor, laminin, neural cell adhesion molecules, and epidermal growth factor. J. Biol. Chem. 267:8544-8557.

Contact Information:

Nemours Biomedical Research
Alfred I. duPont Hospital for Children
1600 Rockland Road
Wilmington, Delaware19803
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Phone: (302) 651-6831
Fax: (302) 651-6895