Soo Young Lee and colleagues, at Ewha Womans University, Republic of Korea, have developed a cell-permeable inhibitor of the mouse protein RANK (which they termed RRI) that is likely to aid in the development of selective drugs to treat diseases that involve substantial bone loss, for example, osteoporosis, periodontitis, and arthritis.
Central to understanding diseases that involve substantial loss of bone density, and thereby loss of bone strength, is insight into the molecules that regulate the formation and function of the cells that slowly breakdown bone, cells known as osteoclasts. One molecule known to regulate both these processes is RANK, however, its utility as a target for drugs that prevent bone destruction might to be limited, as it is involved in many other biological functions. The authors designed RRI to target a region of RANK that they recently found to be specific for the formation of osteoclasts. RRI was found to inhibit in vitro RANKL-induced formation of mouse osteoclasts and in vitro osteoclast-mediated bone destruction. More importantly, it protected against bone loss in two mouse models of diseases associated with bone destruction, leading to the suggestion similar drugs might be beneficial to individuals with diseases that involve bone destruction, such as osteoporosis.