A novel therapeutic vaccine approach, targeting RANKL, prevents bone destruction in bone-related disorders

sence of osteoblasts. Osteoclast formation in this system is strongly inhibited by osteoprotegerin (OPG), which specifically binds to RANKL and suppresses its binding to RANK. The essential role of RANKL-RANK pathways in osteoclast development was further confirmed by a series of knockout mouse experiments. Targeted disruption of either RANKL or RANK induced severe osteopetrosis in mice, and very few osteoclasts were observed in the skeletal tissues of these knockout mice. Conversely, targeted disruption of OPG caused severe osteoporosis, with increased numbers of osteoclasts in their skeletal tissues. Subsequent research has revealed that the osteoclast activation is also regulated by RANKL-RANK pathways. Soluble RANKL not only prolongs the survival of mature osteoclasts but also stimulates their bone-resorbing activity. The administration of OPG induces apoptotic cell death of osteoclasts in vivo. These results strongly suggest that RANKL-RANK pathways are important for normal osteoclast development, and are therefore essential for healthy bone growth.