Case Western Reserve University School of Medicine Orthopaedics ProfessorAppointed: 1990 | |
QualificationsPh.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 InterestsThe underlying principle of our research is to study the cellular & molecular mechanisms that regulate clinically important aspects of bone biology with the long-term goal being to understand the processes in sufficient detail to aid in development of novel therapeutics or diagnostics. With this principle in mind, we currently have three active areas of research:
1. Osseointegration and aseptic loosening of orthopaedic implants. These studies focus on determining whether bacteria impair osseointegration and/or contribute to aseptic loosening as well as counter-measures for impaired osseointegration.
2. The balance between the catabolic and anabolic effects of parathyroid hormone. These studies focus on regulation by Protein Kinase Inhibitor of intracellular signaling pathways induced by parathyroid hormone.
3. Tumorigenesis and metastasis in osteosarcoma. These studies focus on the roles of tyrosine kinases and miRNAs. KeywordsCOS Keywords:'Arthritis', 'Bone Diseases', 'Bone', 'Cancer or Carcinogenesis', 'Connective Tissue', 'Cytokines', 'Inflammation', 'Metastasis', 'Musculoskeletal System', 'Orthopedics', 'Osteoporosis', 'Skeletal Disease', 'Tumors', Diseases and Disorders, Implants, Pathology.Additional Terms:Bone Resorption, Cytokine, Endotoxin, Implant Loosening, Osteoblast, Osteoclast, Osteolysis, Osteosarcoma, PKI, PTH.MembershipsAmerican Society for Bone and Mineral Research International Endotoxin Society Orthopaedic Research Society Honors and Awards2003, 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 Positions1987-1990, 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 P, Garcia R, Abdul-Karim F, Wiersma S, Greenfield E, Getty P (2009) Osteosarcoma, J Amer Acad Orthop Surgeons, In Press
- Unnanuntana A, Bonsignore L, Shirtliff M, Greenfield E (2009) The Effect of Farnesol on Staphylococcus aureus Biofilms and Pre-osteoblasts: An in vitro study, J Bone Joint Surg,, In Press
- 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - Rubin, Murphy, Rahnert, Nanes, Greenfield, Jo, & Fan (2006) Mechanical inhibition of RANKL expression is regulated by H-Ras-GTPase, JBC, 281, 1412-8
- Bi, Nielsen, Kilts, Karsdal, Greenfield, Heegaard, & Young, (2006) Biglycan deficiency increases osteoclast differentation and activity due to defective osteoblasts, Bone, 38, 778-86
- Dai, He, Chen, & Greenfield (2006) TNFa and PTH utilize distinct mechanisms to induce IL-6 and RANKL, Bone, 38, 509-20
- 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - 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
 - Greenfield EM, Bi Y, Miyauchi A, Regulation of osteoclast activity, Life Sciences, 65(11), 1087-102, 1999
 - 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
 - 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
 - Greenfield E M, Goldberg V M, Genetic determination of bone density, Lancet, 350(9087), 1263-4, 1 Nov 1997
 - 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
 - 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
 - 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
 - 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

Profile DetailsIndividual Expertise profile of Edward M. Greenfield, Copyright Edward M. Greenfield. © COS Expertise TM, 2009, ProQuest LLC All rights reserved. |