Musculoskeletal Regeneration

David B. Burr, PhD
Jiliang Li, MD, PhD
Randall J. Roper, PhD
Fengyu Song, DDS, MS, PhD
Stephen Trippel, MD
Charles H. Turner, PhD

David B. Burr, PhD

Positions

• Professor and Chair, Department of Anatomy and Cell Biology
• Professor, Department of Orthopaedic Surgery
• Professor of Biomedical Engineering (IUPUI and Purdue)
• Professor of Anthropology (IUPUI and IU)

Address
Dept. of Anatomy and Cell Biology, MS 5035
Indiana University School of Medicine
Indiana University-Purdue University Indianapolis
635 Barnhill Dr
Indianapolis, IN 46202

Phone: (317) 274-7496
Fax: (317) 278-2040
Email: dburr@iupui.edu

Research Interests

My current research activities include evaluation of the effects of pharmacologic agents used to treat osteoporosis on properties associated with quality of the bone matrix, specifically, the accumulation and repair of microdamage, changes in mineralization and alterations to the collagenous matrix. We are also involved in studying the role that bisphosphonates play in vivo on osteocyte apoptosis, and the direct effects of bisphosphonates on the activity of individual osteoblasts. Related to this, we are performing studies to define the periods for primary and secondary mineralization of bone and how rates of mineralization are affected by anti-remodeling treatments. We have had long-term interests in skeletal fatigue and microdamage-mediated remodeling in bone biomechanical and physiological adaptation.

Recent Publications

• Burr DB. (2003) Microdamage and bone strength. Osteoporos Int 14 (Suppl 5):S67-S72.
• Burr DB (2004) Anatomy and physiology of the mineralized tissues: Role in the pathogenesis of osteoarthrosis. Osteoarthritis and Cartilage 12:S20-S30.
• Allen MR, Hock JM and Burr DB (2004) Periosteum: biology, regulation, and response to osteoporosis therapies. Bone 35:1003-1012.
• Li J, Miller MA, Hutchins GD and Burr DB (2005) Imaging bone microdamage in vivo with positron emission tomography. Bone 37:819-824.
• Ruppel ME, Burr, DB, and Miller LM (2006) Chemical makeup of microdamaged bone differs from undamaged bone. Bone 39:318-324.

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Jiliang Li, MD, PhD

Position

• Assistant Professor

Address
Department of Biology
School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St.
Indianapolis, IN 46202-5132

Phone: (317) 278-1163
Fax: (317) 274-2846
E-mail: jilili@iupui.edu

Research Interests

My research interests are in bone cell biology and bone regeneration. For several years I have studied the mechanisms by which exercise builds bone with the goal of identifying novel drug targets linked to increased bone strength. My research activities include the study of the biological and mechanical aspects of bone using animal models and cell cultures, as well as the study of molecular and cellular mechanisms of mechanotransduction, the process of conversion of mechanical signals into biological signals in bone cells. I am also involved in studying pharmaceutical treatments for osteoporosis and bone fracture. In addition, I am planning to study biology of bone marrow mesenchymal stem cell and its role in bone regeneration.

Recent Publications

• Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH 2006 The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment. J Biol Chem. 18;281(33):23698-711.
• Castillo AB, Alam I, Tanaka SM, Levenda J, Li J, Warden SJ, Turner CH. 2006 Low-amplitude, broad-frequency vibration effects on cortical bone formation in mice. Bone. 39(5):1087-96.
• Iwata K, Li J, Follet H, Burr DB 2006 Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia, Bone, 39(5):1053-8.
• Li J, Liu D, Ke HZ, Duncan RL, Turner CH 2005 Osteogenesis after mechanical loading is linked to the P2X7 nucleotide receptor. J Biol Chem, 280(52):42952-9.
• Li J, Miller MA, Hutchins GD, Burr DB 2005 Imaging bone microdamage in vivo with positron emission tomography. Bone 37(6):819-24.

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Randall J. Roper, PhD

Position

• Assistant Professor

Address
Department of Biology
School of Science
Indiana University-Purdue University Indianapolis
723 W. Michigan St., SL306
Indianapolis, IN 46202

Phone: (317) 274-8131
Fax: (317) 274-2846
E-mail: rjroper@iupui.edu

Research Interests

The neural crest is a transient population of cells found during early embryogenesis and has been termed the “fourth germ layer” because of its developmental mulitpotency. Several tissues with a neural crest component, including craniofacial skeleton, peripheral nervous system, heart, and digestive tract, are affected in individuals with Down syndrome. It has therefore been hypothesized that trisomy 21 causes defects in neural crest cells (NCC). Our work with mouse models of Down syndrome provided the first experimental evidence that trisomy affects neural crest precursors of craniofacial skeleton. Our laboratory is interested in understanding how dosage imbalance of genes on human chromosome 21 affects NCC during development and leads to phenotypes associated with Down syndrome. The deficits caused by trisomy may involve the generation, migration, proliferation, or differentiation of NCC. Using mouse models and in vitro culture systems we want to understand the cellular, genetic, and molecular mechanisms leading to trisomic NCC deficiencies, and identify temporally and spatially specific points for intervention. The long range goal of our work is to discover a molecular therapy to prevent or correct neural crest-related abnormalities in individuals with trisomy.

Recent Publications

• Roper, RJ, Reeves, RH. Understanding the basis for Down syndrome phenotypes. PLoS Genet. 2006 Mar;2(3):e50.
• Roper, RJ, Baxter, LL, Saran, NG, Klinedinst, DK, Beachy, PA, Reeves, RH. Defective cerebellar response to mitogenic Hedgehog signaling in Down syndrome mice.
• Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1452-6. Epub 2006 Jan 23.
• Roper, RJ, St John, HK, Philip, J, Lawler, A, Reeves, RH. Perinatal loss of Ts65Dn Down syndrome mice. Genetics. 2006 Jan;172(1):437-43. Epub 2005 Sep 19.
• Olson LE, Roper RJ, Baxter LL, Carlson EJ, Epstein CJ, Reeves RH. Down syndrome mouse models Ts65Dn, Ts1Cje, and Ms1Cje/Ts65Dn exhibit variable severity of cerebellar phenotypes. Dev Dyn. 2004 Jul;230(3):581-9.

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Fengyu Song, DDS, MS, PhD

Position

• Assistant Professor

Address
Indiana University School of Dentistry
Department of Oral Biology
1121 W. Michigan Street, Room 244
Indianapolis, Indiana 46202

Phone: (317) 274-2415
Fax: (317) 278-1411
Email: fesong@iupui.edu

Research Interests

The research in my laboratory has been focused on the extracellular matrix (ECM) turnover in healthy and diseased tissues, and in the tissue regeneration process. ECM proteinases, including serine proteinases, cystein proteinases, and a group of zinc-dependent endopeptidases known as the matrix metalloproteinases (MMPs), collectively are capable of cleaving most of the major components of the ECM and are believed to be some of the tools by which cells facilitate the ECM remodeling during the degeneration and regeneration process. Specifically we are examining:

• The roles of the serine proteinases and MMPs in the degenerative joint diseases including temporamandibular joint disorder, osteoarthritis, and rheumatoid arthritis to seek the potential marker(s) for disease diagnosis and treatment;
• The roles of MMPs in amphibian limb regeneration using regeneration capable and incapable animal models such as the frog Xenopus laevis, and the axolotl, Ambystoma mexicanum; and
• The induction of the regenerative ability of adult stem cells, including pulp stem cells and gingival fibroblasts, in order to restore the abilities of these cells to regenerate the tooth, the gingival soft tissue and the periodontal bone.

Recent Publications

• Song F, Windsor LJ (2005) Novel non-matrix metalloproteinase mediated collagen degradation. Biochimica et Biophysica Acta (BBA) - General Subjects, 1721(1): 65-72.
• Song F, Wisithprom K, Zhou J, Windsor LJ (2006) Matrix metalloproteinase dependent and independent collagen degradation. Frontiers in Bioscience, 11:3100-20.
• Song F, Bergdoll AS, Windsor LJ (2006) Temporomandibular joint synovial fibroblasts mediate serine proteinase dependent Type I collagen degradation. Biochimica et Biophysica Acta (BBA) - General Subjects, 1760 (10): 1521-1528.
• Ellis M, Song F, Parks ET, Eckert G, Dean J, Windsor LJ (2007) An Evaluation of Toothprints®: DNA yield, quality, and bite registration. J Am Dent Assoc, 138(9):1234-1240.

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Stephen Trippel, MD

Position

• Professor of Orthopaedic Surgery

Address
Department of Orthopaedic Surgery
Indiana University School of Medicine
541 Clinical Drive, Suite 600
Indiana University-Purdue University Indianapolis
Indianapolis, IN 46202

Phone: (317) 278-6904
Fax: (317) 274-3702
Email: strippel@iupui.edu

Research Interests

Arthritis is among the principle causes of disability. This disease reflects damage to the articular cartilage surface of joints. The focus of our research is to identify and apply naturally occurring proteins, known as growth factors, to articular cartilage repair. We are taking a multi-disciplinary approach to this problem, with an emphasis on cellular and molecular biological, and gene therapy technologies.

Recent Publications

• Madry H, Emkey G, Zurakowski D, Trippel SB: 2004 Overexpression of human fibroblast growth factor 2 stimulates all proliferation in an ex vivo model of articular chondrocytes transplantation. J Gene Med. 6: 238-245.
• Trippel SB: 2004 Growth factor inhibition: Potential role in the etiopathogenesis of osteoarthritis. Clin Orthop. 427S:S47-S52.
• Madry H, Cucciarini M, Kaul G, Kohn D, Terwilliger EF, Trippel SB: 2004 Menisci are efficiently transduced by recombinant adeno-associated virus vectors in vitro and in vivo. Amer J Sports Med. 32:1860-1865.
• Cucciarini M, Madry H, Ma C, Thurn T, Zurakowski D, Menger MD, Kohn D, Trippel SB, Terwilliger EF: 2005 Improved tissue repair in articular cartilage defects in vivo by rAAV-mediated overexpression of human fibroblast growth factor 2. Molecular Therapy 12:229-238
• Madry H, Kaul G, Cucchiarini M, Stein U, Zurakowski D, Remberger K, Menger MD, Kohn D, Trippel SB: 2005 Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I). Gene Therapy 12:1171-1179.

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Charles H. Turner, PhD

Positions

• Professor of Biomedical Engineering
• Professor of Orthopaedic Surgery

Address
Orthopaedic Research
1120 South Drive, FH 115
Indiana University-Purdue University Indianapolis
Indianapolis, IN 46202

Phone: (317) 274-3226
Fax: (317) 274-3702
Email: turnerch@iupui.edu

Research Interests

Dr. Turner works on treatments for the bone disease osteoporosis and design of bone implants. Osteoporosis occurs when bone becomes porous due to aging or poor health. In addition, some medications like corticosteroids or immune suppressant drugs can cause osteoporosis. Numerous medications have been developed to fight osteoporosis and several of these were tested in Dr. Turner's laboratory. Dr. Turner's currently research focuses on molecular genetics using transgenic and congenic mice to identify new ways to make bone stronger.

Recent Publications

• Turner, C. H. (2005) The biomechanics of hip fracture. Lancet 366: 98-9.
• Turner, C. H ., A. G. Robling (2004) Exercise as an anabolic stimulus forbone. Current Pharmaceutical Design 10: 2629-2641.
• Roeder, R. K., M. M. Sproul, C. H. Turner (2003) Hydroxyapatite whiskers provide improved mechanical properties in reinforced polymer composites. Journal of Biomedical Materials Research 67A: 801-12.
• Koller, D. L., J. Schriefer, Q. Sun, K. L. Shultz, L. R. Donahue, C. J. Rosen, T. Foroud, W. G. Beamer, C. H. Turner (2003) Genetic effects for femoral biomechanics, structure, and density in C57BL/6J and C3H/HeJ inbred mouse strains. Journal of Bone and Mineral Research 18: 1758-1765.
• Ahlborg, H. G., O. Johnell, C. H. Turner , G. Rannevik, M. K. Karlsson (2003) Bone loss and bone size after menopause. New England Journal of Medicine 349: 327-334.

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