Osteoprotegerin and Adhesion Molecules - Adhesion Molecules - page 279

SUMMARY

• Circulating concentrations of osteoprotegerin are increased in patients
with a number of pathologies, many of which are associated with
inl ammation.

• Human cell culture studies indicate that osteoprotegerin can promote
leukocyte adhesion via a number of mechanisms.

• h e in vivo importance of these in vitro i ndings is currently unclear.

Abbreviations

Ang-2 angiopoietin-2

CD62E E-selectin

HMVEC human microvascular endothelial cell

HUVEC human umbilical vein endothelial cell

ICAM-1 intercellular adhesion molecule 1

IL-1b interleukin-1 beta

mRNA messenger ribonucleic acid

OPG osteoprotegerin

PMN primary polymorphonuclear neutrophil

RANKL receptor activator of NF-кB ligand

RANK receptor activator of NF-кB

siRNA small interfering RNA

TNF-α tumour necrosis factor alpha

TRAIL tumour necrosis factor-related apoptosis-inducing ligand

VCAM-1 vascular cell adhesion molecule 1

VSMC vascular smooth muscle cells

Key Facts about the Interaction between Osteoprotegerin,
Inflammation and Adhesion Molecules

1. In human subjects, high circulating levels of OPG have been associated with
a number of diseases where inl ammation is integral in the pathology.

2. In human cells in vitro , OPG stimulates leukocyte adhesion.

3. h e mechanisms by which OPG stimulates leukocyte adhesion in human
cells is currently controversial but may involve a number of mechanisms:

(a) the ability of OPG to sensitize the endothelial to TNF-α-mediated
upregulation of adhesion molecules;