Research Assistant Professor
Division of Oral and Maxillofacial Pathology
Department of Diagnostic and Biological Sciences
Biology, B.A., St. Olaf College, 1991-1995
Biology, Ph.D., University of Colorado, 1997-2003
16-146 Moos Tower
515 Delaware St. SE
Minneapolis, MN 55455
My major interests are in understanding transcriptional gene regulatory mechanisms and signal transduction pathways that contribute to bone health and disease.
Transcriptional Regulation of Osteoblasts by HDAC7 and Runx2
Osteoblasts are the cells responsible for building new bone. There is great need in many orthopedic and dental conditions for new therapies to enhance bone growth and regeneration by osteoblasts. Formation of osteoblasts from mesenchymal stem cells involves Runx2, a transcription factor often called the master regulator of osteoblasts. Runx2 binds to the promoters of numerous target genes and can either activate or repress expression of these targets. I showed that Runx2 represses gene expression by recruiting Histone Deacetylase 7 to its targets. Loss of HDAC7 enhances osteoblast formation in cell culture suggesting that the Runx2-HDAC7 interaction might be a novel target to enhance bone growth. I then found that Bone Morphogenetic Protein signaling activates PKD to disrupt Runx2-HDAC7 interaction. Current projects in my lab include characterizing the effect of osteoblast-specific deletion of HDAC7 in mice, and investigating other partners and targets of HDAC7 in osteoblasts.
Regulation of Osteoclasts by HDACs and BMPs
Bone is broken down or resorbed by specialized multiucleated cells called osteoclasts. While this is an important part of normal bone maintenance and repair of damaged bone, excessive osteoclast activity leads to destructive bone loss in many cancers, arthritis, and periodontal disease and can contribute to loosening or failure of dental or orthopedic implants. Consequently there is a need to better understand the factors that regulate osteoclast formation and activity.
The transcription factor MITF is recruited at an early stage of osteoclast formation to the promoters of genes necessary for their differentiation but expression of these genes remains off until cells receive additional signals. I began a collaboration with Dr. Kim Mansky in which we used cell culture models to find that Histone Deacetylase 7 binds to MITF and represses transcription of osteoclast genes. Binding of HDAC7 to MITF is disrupted by the RANK Ligand cytokine, allowing gene expression and differentiation to proceed. We are following up on these studies to identify and understand other targets of HDAC7 in osteoclasts and how they are regulated.
Another collaborative project in my lab has been studying how BMP signaling regulates osteoclasts. BMPs are used clinically to promote bone growth and healing by osteoblasts. Working with Drs. Raj Gopalakrishnan, Kim Mansky and Anna Petryk, our group found that BMPs can also act directly on osteoclasts to increase bone resorption. This effect may contribute to destabilization or failure of bone regeneration protocols. We are currently using a variety of in vivo and in vitro models to determine the signal transduction pathways used by BMPs in osteoclasts.
Member, School of Dentistry Institutional Effectiveness Committee, 2011-present
Member, American Society for Bone & Mineral Research, 2008-present
Volunteer at Society for Developmental Biology Annual Meeting, Boulder, CO. June 2000
Committee for Graduate Student Affairs, Department of Molecular, Cellular and Developmental Biology, University of Colorado. 1999-2000
Mansky KC*, Jensen ED*, Davidova J, Yamamoto M, Gopalakrishnan R. *Co-corresponding authors (2013) Protein kinase D promotes in vitro osteoclast differentiation and fusion. J Biol Chem. 2013 Apr 5;288(14):9826-34. PMID: 23430742
Basi DL, Hughes PJ, Thumbigere-Math V, Sabino M, Mariash A, Lunos SA, Jensen E, Gopalakrishnan R (2011) Matrix metalloproteinase-9 expression in alveolar extraction sockets of Zoledronic acid-treated rats. J Oral Maxillofac Surg. 2011 Nov; 69(11):2698-707. PMID: 21752506
Zhang H, Pan Y, Zheng L, Choe C, Lindgren B, Jensen ED, Westendorf JJ, Cheng L, Huang H. (2011) FOXO1 Inhibits Runx2 transcriptional activity and prostate cancer cell migration and invasion. Cancer Res. 71(9): 3257-67. PMID: 21505104
Pham L, Beyer K, Jensen ED, Rodriguez JS, Davydova J, Yamamoto M, Petryk A, Gopalakrishnan R, Mansky KC. (2011) Bone morphogenetic protein 2 signaling in osteoclasts is negatively regulated by the BMP antagonist, twisted gastrulation. J Cell Biochem. 112(3):793-803. PMID: 21328453
Pham L, Kaiser B, Romsa A, Schwarz T, Gopalakrishnan R, Jensen ED*, Mansky KC*. *Co-corresponding authors. (2011) HDAC3 and HDAC7 have opposite effects on osteoclast differentiation. J Biol Chem. Published online 2/15/11. PMID: 21324898
Jensen ED, Gopalakrishnan R, Westendorf JJ. (2010) Regulation of gene expression in osteoblasts. Biofactors. 36(1): 25-32. PMID: 20087883
Schwarz T, Sohn C, Kaiser B, Jensen ED, Mansky KC (2010) The 19S proteosomal lid subunit POH1 enhances the transcriptional activation by Mitf in osteoclasts. J Cell BioChem. 109(5): 967-74. PMID: 20058232
Jensen ED, Pham L, Billington CJ Jr., Espe K, Carlson A, Westendorf JJ, Petryk A, Gopalakrishnan R, Mansky K. (2010) Bone Morphogeneic Protein 2 Directly EnhancesDifferentiation of Murine Osteoclast Precursors. J Cell Biochem. 109(4): 672-82. PMID: 20039313
Hoeppner LH, Secreto F, Jensen ED, Li X, Kahler R, Westendorf JJ. (2010) Runx2 and Bone Morphogenic Protein 2 Regulates the Expression of an Alternative Lef1 Transcript During Osteoblast Maturation. J Cell Physiol. 221(2): 480-9. PMID: 19650108.
Li X, Hoeppner LH, Jensen ED, Gopalakrishnan R, Westendorf JJ. (2009) Coactivator activator (CoAA) prevents the transcriptional activity of RUNT Domain transcription factors. J Cell Biochem. 108(2):378-87. PMID: 19585539.
Sotillo-Rodriguez, J, Mansky KC, Jensen ED, Carlson AE, Schwarz T, MacKenzie B, Prasad H, Roher MD, Petryk A, Gopalakrishnan R. (2009) Enhanced osteoclastogenesis causes ostepenia in Twisted gastrulation-deficient mice. J Bone Miner Res. 24(11): 1917-26. PMID: 19419314.
Suttumanatwong S*, Jensen ED*, Schilling J, Franceschi RT, Carlson AE, Mansky MC, Gopalakrishnan R. (* co-first authors) (2009) Sp Proteins and Runx2 mediate regulation of matrix Gla protein (MGP) expression by parathyroid hormone. J Cell Biochem. 107(2): 284-292. 19306294.
Jensen ED, Gopalakrishnan R, Westendorf JJ. (2009) Bone morphogenic protein 2 activates protein kinase D to regulate histone deacetylase 7 localization and repression of RUNX2. J Biol Chem. 284(4): 2225-34. PMID: 19029091.
Schlosser G, Awtry T, Brugmann SA, Jensen ED, Neilson K, Ruan G, Stammler A, Voelker D, Yan B, Zhang C, Klymkowsky MW, Moody SA. (2008) Eya1 and Six1 promote neurogenesis in the cranial placodes in a SoxB1-dependent fashion. Dev Biol. 320(1): 199-214. PMID: 18571637.
Kahler RA, Yingst SMC, Hoeppner LH, Jensen ED, Krawczak D, Oxford JT, Westendorf JJ. (2008) Collagen 11a1 is Indirectly Activated by Lymphocyte Enhancer binding Factor 1 (Lef1) and Negatively Regulates Osteoblast Maturation. Matix Biology. 27(4): 330-38. PMID: 18280717.
Jensen ED, Schroeder TM, Bailey J, Gopalakrishnan R, Westendorf JJ. (2008) Histone Deaceylase 7 Associates with Runx2 and Represses Its Activity During Osteoblast Maturation in a Deacetylation-Independent Manner. J Bone Miner Res 23(3): 361-72. PMID: 17997710.
Jensen ED, Niu, L, Caretti G, Nicol S, Teplyuk N, Stein GS, Sartorelli, V, VanWijnen AJ, Fuller-Pace FV, Westendorf JJ. (2008) Ddx5 (p68) Interacts with Runx2 and Regulates Osteoblast Differentiation. J Cell Biochem. 103(5): 1438-51. PMID: 17960593.
Jensen ED, Nair AK, Westendorf JJ. (2007). Histone Deacetylase Co-Repressor Complex Control of Runx2 and Bone Formation. Crit. Reviews Euk Gene Express 17(3): 187-96. PMID: 17725488.
Schroeder TM*, Jensen ED*, Westendorf JJ. (* Equal contributions). (2005). Runx2: A master organizer of gene transcription in developing and maturing osteoblasts. Birth Defects Res C Embryo Today 75(3): 213-25. PMID: 16187316,
Zhang C, Basta T, Jensen ED, Klymkowsky MW. (2003). The -catenin/ VegT- regulated early zygotic gene Xnr5 is a direct target of Sox3 regulation. Development 130(23): 5609-24. PMID: 14522872.