Osteoprotegerin (OPG), a decoy receptor secreted by osteoblasts, is a major negative
regulator of bone resorption. It functions by neutralizing the receptor activator of nuclear
factor κB ligand (RANKL), which plays a central role in promoting osteoclastogenesis. OPG
is known to be a high-affinity heparan sulfate (HS)-binding protein. Presumably, HS could
regulate the function of OPG and affect how it inhibits RANKL. However, the molecular detail
of HS-OPG interaction remains poorly understood, which hinders our understanding of how …