Biomedical Engineering Reference
In-Depth Information
18
CHAPTER
Osteoprotegerin and Adhesion
Molecules
Catherine Rush
1
and Jonathan Golledge
2, *
1
Vascular Biology Unit, School of Medicine and Dentistry, James Cook University,
Douglas, QLD 4811, E-mail:
Catherine.Rush@jcu.edu.au
2
Vascular Biology Unit, School of Medicine and Dentistry, James Cook University,
Douglas, QLD 4811, E-mail:
jonathan.golledge@jcu.edu.au
ABSTRACT
h e glycoprotein osteoprotegerin (OPG) plays an important role in controlling
normal bone remodelling by inhibiting osteoclast function. More recently, OPG
has been implicated in a number of diseases associated with inl ammation. h is
chapter describes current work being undertaken to try and understand the
mechanisms underlying the association between high circulating levels of OPG
and inl ammatory pathologies. Human
in vitro
work suggests OPG promotes
leukocyte adhesion via at least two mechanisms. It stimulates the upregulation of
angiopoietin-2 within endothelium, thereby promoting endothelial responsiveness
to the pro-inl ammatory cytokine tumour necrosis factor alpha. h us, OPG acts
in concert with pro-inl ammatory cytokines to promote adhesion molecule
upregulation and favour leukocyte recruitment. It also has the ability to cause
rapid increases in leukocyte adhesion to the endothelium by acting as a direct
bridge between leukocytes and endothelial cells. Despite this convincing data for a
pro-inl ammatory role of OPG in human cells,
in vitro
studies in knockout mouse
models have not coni rmed the role of OPG in inl ammation. h e reason for this
disparity is currently unknown. Further studies using dif erent animal models
and alternative ways of studying human disease will be required to clarify these
disparities.
