ABSTRACT
Th 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 infl ammation. Th is chapter describes current work being undertaken to try and understand the mechanisms underlying the association between high circulating levels of OPG and infl 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-infl ammatory cytokine tumour necrosis factor alpha. Th us, OPG acts in concert with pro-infl 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-infl ammatory role of OPG in human cells, in vitro studies in knockout mouse models have not confi rmed the role of OPG in infl ammation. Th e reason for this disparity is currently unknown. Further studies using diff erent animal models and alternative ways of studying human disease will be required to clarify these disparities.
