David T. Denhardt, PhD, Rutgers University

David T. Denhardt, PhD
David T. Denhardt, PhD

A major focus of the Denhardt laboratory is the study of osteopontin (OPN). OPN is an O-glycosylated phosphoprotein that is synthesized in a variety of tissues and cells and secreted into body fluids. In the immune system, OPN is expressed by many different cell types, including macrophages, neutrophils, dendritic cells, NK cells, and T and B lymphocytes; it is up-regulated in response to injury and inflammation in every organ examined; for example, cardiac tissue, kidney, lung, bone, brain, the gastrointestinal tract, joints, liver, adipose tissue and most tumors. OPN has been identified as a biomarker for various types of cancers and inflammatory diseases. Excessive or dysregulated OPN expression has been linked to the pathogenesis of both autoimmune disorders such as multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, atherosclerosis and other inflammatory diseases including cardiovascular disease, chronic obstructive pulmonary disease, inflammatory bowel disease, liver disease and asthma. Although initially regarded as an RGD-containing adhesive bone matrix protein because of its presence in the extracellular matrix of mineralized tissues, it is now established as a soluble cytokine/hormone capable of stimulating signal transduction pathways in many different cell types.

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References

  1. Kazanecki CC, Kowalski AJ, Ding T, Rittling SR, Denhardt DT. Characterization of anti-osteopontin monoclonal antibodies: Binding sensitivity to post-translational modifications. J Cell Biochem. 2007 Nov 1;102(4):925-35.
  2. Wang KX, Denhardt DT. Osteopontin: role in immune regulation and stress responses. Cytokine Growth Factor Rev. 2008 Oct-Dec;19(5-6):333-45.
  3. Christensen B, Klaning E, Nielsen MS, Andersen MH, Sorensen ES. C-terminal Modification of Osteopontin Inhibits Interaction with the αVβ3-Integrin. J Biol Chem. 2012 February 3; 287(6): 3788â??3797.
  4. Wang KX, Shi YF, Ron Y, Kazanecki CC, Denhardt DT. Plasma osteopontin modulates chronic restraint stress-induced thymus atrophy by regulating stress hormones: inhibition by an anti-osteopontin monoclonal antibody. J Immunol. 2009 Feb 15;182(4):2485-91.
  5. Nagao M, Feinstein TN, Ezura Y, Hayata T, Notomi T, Saita Y, Hanyu R, Hemmi H, Izu Y, Takeda S, Wang K, Rittling S, Nakamoto T, Kaneko K, Kurosawa H, Karsenty G, Denhardt DT, Vilardaga JP, Noda M. Sympathetic control of bone mass regulated by osteopontin. Proc Natl Acad Sci U S A. 2011 Oct 25;108(43):17767-72.