Antiresorptive activity of osteoprotegerin requires an intact heparan sulfate-binding site
Miaomiao Li, Ding Xu
Abstract
Significance Osteoprotegerin (OPG) plays an essential role in bone remodeling by inhibiting receptor activator of nuclear factor B ligand (RANKL), which drives osteoclastogenesis. While much is known about OPG–RANKL interaction, the exact biological function of the C-terminal domains of OPG remains a mystery. One likely function of the C-terminal domains of OPG is to interact with heparan sulfate (HS), a glycosaminoglycan that is abundantly expressed by osteoblast lineage cells. However, the physiological importance of OPG–HS interactions in bone remodeling remains uncertain. Here, by using two strains of transgenic mice, both of which have altered OPG–HS interactions, we have definitively shown that binding to osteoblast HS is indispensable for the antiresorptive function of OPG in bone remodeling.