ABSTRACT
A number of groups have investigated the eff ect of OPG defi ciency or excess in mouse models, although its eff ects on infl ammation have not been central to these studies (Bucay et al. 1998, Bennett et al. 2006, Morony et al. 2008). A number of groups have demonstrated that OPG defi ciency promotes aortic calcifi cation to varying degrees depending on the genetic background of the mice (Bucay et al. 1998, Bennett et al. 2006). Infl ammation is commonly associated with vascular calcifi cation and thus this fi nding is counter-intuitive given the data presented about the pro-infl ammatory eff ects of OPG. Indeed, in one mouse model (the hyperlidaemia mouse defi cient in apo lipoprotein e), OPG defi ciency appears to promote atherosclerosis, where infl ammation is believed to play an important role (Bennett et al. 2006). Th e latter fi ndings are not confi rmed in all studies in this area. Th us, in the mouse model of atherosclerosis defi cient in low-density lipoprotein receptor, upregulating OPG appears to have no eff ect on atherosclerosis progression (Morony et al. 2008). On the basis of human association data, OPG would be expected to promote atherosclerosis. Th e fi ndings from mouse models are thus currently diffi cult to interpret in terms of the large amount of human association data linking high levels of OPG with a number of diff erent infl ammation-associated diseases. A number of possibilities exist, such as that the positive association between OPG and infl ammation-associated diseases is simply a consequence of the process with no role in the infl ammation itself. It is also likely that infl ammation pathways within mice do not completely refl ect the situation in humans, as has been seen with a number of cytokines.
