Edward M. Greenfield

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Case Western Reserve University
School of Medicine
Orthopaedics
ProfessorAppointed: 1990

Mailing Address

2109 Adelbert Road
Biomedical Research Building
Room 331
Cleveland, Ohio 44106
United States

Contact Information

Phone: (216) 368-1331
Fax: (216) 368-1332
emg3@po.cwru.edu

Qualifications

Ph.D., University of North Carolina at Chapel Hill, Marine Science, 1987.
M.S., University of North Carolina at Chapel Hill, Marine Science, 1981.
B.A., New College, Biology, 1978.

Expertise and Research Interests

Our research focuses on cellular mechanisms that regulate bone turnover in response to stimuli such as hormones, cytokines, orthopaedic wear particles, and bacterial endotoxin. We study signal transduction, regulation of gene expression, and differentiation of bone cells (osteoclasts and osteoblasts). These studies use cell cultures as well as in vivo mouse models. The role of specific molecules are studied using a variety of techniques, including gene knock out, gene knock down (siRNA and antisense), and neutralizing antibodies. These studies have important implications for regulation of bone turnover in various diseases, including osteoporosis, loosening of orthopaedic implants, and tumors. Specific areas of current research include: the role of bacteria in "aseptic loosening" of orthopaedic implants, regulation of parathyroid hormone signaling by Protein Kinase Inhibitor, regulation of bone turnover by the gp130 family of cytokines, and novel tumor supressors/oncogenes in bone tumors.

Keywords

COS Keywords:

Arthritis, Bone, Bone Diseases, Cancer Or Carcinogenesis, Connective Tissue, Cytokines, Diseases and Disorders, Implants, Inflammation, Metastasis, Musculoskeletal System, Orthopedics, Osteoporosis, Pathology, Skeletal Disease, Tumor Immunology, Tumors.

Additional Terms:

Bone Resorption, Cytokine, Endotoxin, Implant Loosening, Osteoblast, Osteoclast, Osteolysis, Osteosarcoma, PKI, PTH.

Memberships

American Society for Bone and Mineral Research
International Endotoxin Society
Orthopaedic Research Society

Honors and Awards

2003, Kappa Delta Award for Outstanding Orthopaedic Research, American Academy of Orthopaedic Surgeons
1999, William Harris Award for Orthopaedic Research Related to the Hip, Orthopaedic Research Society

Previous Positions

1987-1990, Postdoctoral Fellow, Washington University in St. Louis, Jewish Hospital, Pathology

Funding Received

  • National Institutes of Health (NIH): In vivo regulation of cAMP/PKA signaling by PKIgamma, 2007 to 2009.
  • National Institutes of Health (NIH): Termination of PTH Responses in Osteoblasts, 2003 to 2007.
  • National Institutes of Health (NIH): Support of osteoclast differentiation by mesenchymal cells, 2002 to 2006.
  • National Institutes of Health (NIH): Cellular Mechanisms of Implant Loosening, 2000 to 2005.

Publications

  • Messerschmitt PJ, Rettew AN, Brookover RE, Garcia RM, Getty PJ, Greenfield EM (Sep 2008) Specific tyrosine kinase inhibitors regulate human osteosarcoma cells in vitro., Clinical orthopaedics and related research, 466 (9), 2168-75 Abstract
  • Beidelschies MA, Huang H, McMullen MR, Smith MV, Islam AS, Goldberg VM, Chen X, Nagy LE, Greenfield EM (Jul 2008) Stimulation of macrophage TNFalpha production by orthopaedic wear particles requires activation of the ERK1/2/Egr-1 and NF-kappaB pathways but is independent of p38 and JNK., Journal of cellular physiology, 217 (3), 652-666 Abstract
  • Beidelschies MA, Huang H, McMullen MR, Smith MV, Islam AS, Goldberg VM, Chen X, Nagy LE, Greenfield EM (Jul 2008) Stimulation of macrophage TNFalpha production by orthopaedic wear particles requires activation of the ERK1/2/Egr-1 and NF-kappaB pathways but is independent of p38 and JNK., Journal of cellular physiology, 217 (3), 652-666 Abstract
  • Greenfield EM, Bechtold J (2008) What other biologic and mechanical factors might contribute to osteolysis?, The Journal of the American Academy of Orthopaedic Surgeons, 16 Suppl 1, S56-62 Abstract
  • Greenfield & Chen (2008) Use of siRNA and antisense knockdown to study regulation of PKA by PKI, Handbook of Cell Signaling, Elsevier, In Press (bookchapter)
  • Smith MV, Lee MJ, Islam AS, Rohrer JL, Goldberg VM, Beidelschies MA, Greenfield EM (May 2007) Inhibition of the PI3K-Akt signaling pathway reduces tumor necrosis factor-alpha production in response to titanium particles in vitro., The Journal of bone and joint surgery. American volume, 89 (5), 1019-27 Abstract
  • Chen X, Song IH, Dennis JE, Greenfield EM (May 2007) Endogenous PKI gamma limits the duration of the anti-apoptotic effects of PTH and beta-adrenergic agonists in osteoblasts., Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 22 (5), 656-64 Abstract
  • Taki N, Tatro JM, Lowe R, Goldberg VM, Greenfield EM (May 2007) Comparison of the roles of IL-1, IL-6, and TNFalpha in cell culture and murine models of aseptic loosening., Bone, 40 (5), 1276-83 Abstract
  • Smith MV, Lee MJ, Islam AS, Rohrer JL, Goldberg VM, Beidelschies MA, Greenfield EM (May 2007) Inhibition of the PI3K-Akt signaling pathway reduces tumor necrosis factor-alpha production in response to titanium particles in vitro., The Journal of bone and joint surgery. American volume, 89 (5), 1019-27 Abstract
  • Tatro JM, Taki N, Islam AS, Goldberg VM, Rimnac CM, Doerschuk CM, Stewart MC, Greenfield EM (Mar 2007) The balance between endotoxin accumulation and clearance during particle-induced osteolysis in murine calvaria., Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 25 (3), 361-9 Abstract
  • Nalepka JL, Lee MJ, Kraay MJ, Marcus RE, Goldberg VM, Chen X, Greenfield EM (Oct 2006) Lipopolysaccharide found in aseptic loosening of patients with inflammatory arthritis., Clinical orthopaedics and related research, 451, 229-35 Abstract
  • Fan X, Rahnert JA, Murphy TC, Nanes MS, Greenfield EM, Rubin J (May 2006) Response to mechanical strain in an immortalized pre-osteoblast cell is dependent on ERK1/2., Journal of cellular physiology, 207 (2), 454-60 Abstract
  • Dai, He, Chen, & Greenfield (2006) TNFa and PTH utilize distinct mechanisms to induce IL-6 and RANKL, Bone, 38, 509-20
  • Bi, Nielsen, Kilts, Karsdal, Greenfield, Heegaard, & Young, (2006) Biglycan deficiency increases osteoclast differentation and activity due to defective osteoblasts, Bone, 38, 778-86
  • Rubin, Murphy, Rahnert, Nanes, Greenfield, Jo, & Fan (2006) Mechanical inhibition of RANKL expression is regulated by H-Ras-GTPase, JBC, 281, 1412-8
  • Greenfield (2006) Particulate Matter and Host Reactions, Encycolopedia of Biomaterials and Biomedical Engineering, Taylor Francis (bookchapter)
  • Taki N, Tatro JM, Nalepka JL, Togawa D, Goldberg VM, Rimnac CM, Greenfield EM, Polyethylene and Titanium Particles Induce Osteolysis By Similar, Lymphocyte-independent, Mechanisms., Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society., 23(2), 376-83, Mar 2005 Abstract
  • Chen X, Dai JC, Orellana SA, Greenfield EM, Endogenous Protein Kinase Inhibitor Gamma Terminates Immediate-early Gene Expression Induced By CAMP-dependent Protein Kinase (PKA) Signaling: Termination Depends on PKA Inactivation Rather Than PKA Export From The Nucleus., The Journal of Biological Chemistry, 280(4), 2700-7, Jan 2005 Abstract
  • Greenfield EM, Bi Y, Ragab AA, Goldberg VM, Nalepka JL, Seabold JM, Does Endotoxin Contribute to Aseptic Loosening of Orthopedic Implants?, Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 72(1), 179-85, Jan 2005 Abstract
  • J Rubin, EM Greenfield (2005) Osteoclast origin and differentiation, Bone Resorption, Springer-Verlag, 1-23 pages (bookchapter)
  • Nalepka JL, Greenfield EM, Detection of bacterial endotoxin in human tissues, Biotechniques, 37(3), 413-7, Sep 2004 Abstract
  • Chen X, Dai JC, Greenfield EM, Termination of immediate-early gene expression after stimulation by parathyroid hormone or isoproterenol, American Journal of Physiology. Cell Physiology, 283(5), C1432-40, November 2002 Abstract
  • Ragab AA, Nalepka JL, Bi Y, Greenfield EM, Cytokines synergistically induce osteoclast differentiation: support by immortalized or normal calvarial cells, American Journal of Physiology. Cell Physiology, 283(3), C679-87, September 2002 Abstract
  • Bi Y, Collier TO, Goldberg VM, Anderson JM, Greenfield EM, Adherent endotoxin mediates biological responses of titanium particles without stimulating their phagocytosis, Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society., 20(4), 696-703, July 2002 Abstract
  • Greenfield EM, Einhorn TA, Calcium Homeostasis, Orthopaedics (edited by Fitzgerald, Kaufer, & Malkani), 195-200, 2002
  • Greenfield EM, Bi Y, Ragab AA, Goldberg VM, Van De Motter RR, The role of osteoclast differentiation in aseptic loosening, Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 20(1), 1-8, January 2002 Abstract
  • Bi Y, Seabold JM, Kaar SG, Ragab AA, Goldberg VM, Anderson JM, Greenfiel EM, Adherent endotoxin on orthopedic wear particles stimulates cytokine production and osteoclast differentiation, Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 16(11), 2082-91, November 2001 Abstract
  • Bi Y, Van De Motter RR, Ragab AA, Goldberg VM, Anderson JM, Greenfield EM, Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclasts, Journal of Bone and Joint Surgery. American Volume, 83-A(4), 501-8, April 2001 Abstract
  • Kaar SG, Ragab AA, Kaye SJ, Kilic BA, Jinno T, Goldberg VM, Bi Y, Stewart MC, Carter JR, Greenfield EM, Rapid repair of titanium particle-induced osteolysis is dramatically reduced in aged mice, Journal of Orthopaedic Research, 19(2), 171-8, March 2001 Abstract
  • Ragab AA, Van De Motter R, Lavish SA, Goldberg VM, Ninomiya JT, Carlin CR, Greenfield EM, Measurement and removal of adherent endotoxin from titanium particles and implant surfaces, Journal of Orthopaedic Research, 17(6), 803-9, November 1999 Abstract
  • Greenfield EM, Bi Y, Miyauchi A, Regulation of osteoclast activity, Life Sciences, 65(11), 1087-102, 1999 Abstract
  • Ninomiya JT, Bi Y, Banks MA, Lavish SA, Goldberg VM, Greenfield EM, Bone marrow cells produce soluble factors that inhibit osteoclast activity, Journal of Orthopaedic Research, 17(1), 51-8, Jan 1999 Abstract
  • Ragab A A, Lavish S A, Banks M A, Goldberg V M, Greenfield E M, Osteoclast differentiation requires ascorbic acid, Journal of Bone and Mineral Research, 13(6), 970-7, June 1998 Abstract
  • Greenfield E M, Goldberg V M, Genetic determination of bone density, Lancet, 350(9087), 1263-4, 1 Nov 1997 Abstract
  • Greenfield EM, The role of interleukin-6 in stimulation of bone resorption by parathyroid hormone, Cells and Materials, 7, 301-12, 1997
  • Pollock J H, Blaha M J, Lavish S A, Stevenson S, Greenfield E M, In vivo demonstration that parathyroid hormone and parathyroid hormone-related protein stimulate expression by osteoblasts of interleukin-6 and leukemia inhibitory factor, Journal of Bone and Mineral Research, 11(6), 754-9, June 1996 Abstract
  • Greenfield E M, Horowitz M C, Lavish S A, Stimulation by parathyroid hormone of interleukin-6 and leukemia inhibitory factor expression in osteoblasts is an immediate-early gene response induced by cAMP signal transduction, Journal of Biological Chemistry, 271(18), 10984-9, 3 May 1996 Abstract
  • Greenfield EM, The role of interleukin-6 in stimulation of osteoclast differentiation and activity by neuropeptides and other bone resorptive agents, Biological Mechanisms of Tooth Movement and Craniofacial Adaptation, 301-7, 1996
  • Greenfield E M, Shaw S M, Gornik S A, Banks M A, Adenyl cyclase and interleukin 6 are downstream effectors of parathyroid hormone resulting in stimulation of bone resorption, Journal of Clinical Investigation, 96(3), 1238-44, September 1995 Abstract
  • Greenfield E M, Gornik S A, Horowitz M C, Donahue H J, Shaw S M, Regulation of cytokine expression in osteoblasts by parathyroid hormone: rapid stimulation of interleukin-6 and leukemia inhibitory factor mRNA, Journal of Bone and Mineral Research, 8(10), 1163-71, October 1993 Abstract

Profile Details

Last Verified: 9/29/2008

COS Expertise ID #246544
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